Targeted therapies have revolutionized the treatment of numerous different cancer types and ushered in an era of personalized medicine, yet they can be prohibitively costly. As patent protection expires on many of the first FDA-approved monoclonal antibodies developed for oncologic indications, the doors are opened for other companies to develop their own version of these drugs, known as biosimilars. The price of biosimilars is expected to be considerably lower than the original drugs upon which they are based.

Bevacizumab-awwb, marketed as Mvasi by Amgen and Allergen, became the first such drug to receive approval by the US Food and Drug Administration for the treatment of cancer in fall last year.¹ It is a biosimilar of Genentech’s anti-angiogenesis drug, bevacizumab (Avastin), a monoclonal antibody that targets vascular endothelial growth factor-A (VEGF-A).

Targeted therapies have revolutionized the treatment of numerous different cancer types and ushered in an era of personalized medicine, yet they can be prohibitively costly. As patent protection expires on many of the first FDA-approved monoclonal antibodies developed for oncologic indications, the doors are opened for other companies to develop their own version of these drugs, known as biosimilars. The price of biosimilars is expected to be considerably lower than the original drugs upon which they are based.

Bevacizumab-awwb, marketed as Mvasi by Amgen and Allergen, became the first such drug to receive approval by the US Food and Drug Administration for the treatment of cancer in fall last year.¹ It is a biosimilar of Genentech’s anti-angiogenesis drug, bevacizumab (Avastin), a monoclonal antibody that targets vascular endothelial growth factor-A (VEGF-A).

Targeted therapies have revolutionized the treatment of numerous different cancer types and ushered in an era of personalized medicine, yet they can be prohibitively costly. As patent protection expires on many of the first FDA-approved monoclonal antibodies developed for oncologic indications, the doors are opened for other companies to develop their own version of these drugs, known as biosimilars. The price of biosimilars is expected to be considerably lower than the original drugs upon which they are based.

Bevacizumab-awwb, marketed as Mvasi by Amgen and Allergen, became the first such drug to receive approval by the US Food and Drug Administration for the treatment of cancer in fall last year.¹ It is a biosimilar of Genentech’s anti-angiogenesis drug, bevacizumab (Avastin), a monoclonal antibody that targets vascular endothelial growth factor-A (VEGF-A).

The human epidermal growth factor receptor-2 (HER2)-targeting monoclonal antibody trastuzumab-dkst, was approved by the US Food and Drug Administration in 2017 for the treatment of patients with HER2-positive breast or metastatic gastric or gastroesophageal junction adenocarcinoma.¹ Trastuzumab-dkst, marketed as Ogviri by Mylan NV and Biocon Ltd, is a copy, known as a biosimilar, of Genentech’s trastuzumab (Herceptin), which has been approved in the US since 1998. Genentech’s patent on trastuzumab expires in 2018, paving the way for other companies to produce their own versions of this targeted therapy. It becomes the second biosimilar approved for a cancer indication, following approval of a bevacizumab biosimilar earlier last year.

The human epidermal growth factor receptor-2 (HER2)-targeting monoclonal antibody trastuzumab-dkst, was approved by the US Food and Drug Administration in 2017 for the treatment of patients with HER2-positive breast or metastatic gastric or gastroesophageal junction adenocarcinoma.¹ Trastuzumab-dkst, marketed as Ogviri by Mylan NV and Biocon Ltd, is a copy, known as a biosimilar, of Genentech’s trastuzumab (Herceptin), which has been approved in the US since 1998. Genentech’s patent on trastuzumab expires in 2018, paving the way for other companies to produce their own versions of this targeted therapy. It becomes the second biosimilar approved for a cancer indication, following approval of a bevacizumab biosimilar earlier last year.

The human epidermal growth factor receptor-2 (HER2)-targeting monoclonal antibody trastuzumab-dkst, was approved by the US Food and Drug Administration in 2017 for the treatment of patients with HER2-positive breast or metastatic gastric or gastroesophageal junction adenocarcinoma.¹ Trastuzumab-dkst, marketed as Ogviri by Mylan NV and Biocon Ltd, is a copy, known as a biosimilar, of Genentech’s trastuzumab (Herceptin), which has been approved in the US since 1998. Genentech’s patent on trastuzumab expires in 2018, paving the way for other companies to produce their own versions of this targeted therapy. It becomes the second biosimilar approved for a cancer indication, following approval of a bevacizumab biosimilar earlier last year.

Biosimilars have arrived, and chances are that you’re already prescribing them. Last September, the US Food and Drug Administration (FDA) approved the first cancer-specific biosimilar, bevacizumab-awwb, for multiple cancer types (p. e60);¹ and in November, it approved trastuzumab-dkst for HER2-positive breast and gastrointestinal cancers (p. e63).¹ Briefly, biosimilars are biologic products that show comparable quality, efficacy, and safety to an existing, approved biologic known as the reference product.

Small-molecule drugs such as aspirin are easy to replicate identically, whereas biosimilars are large, complex proteins that are manufactured in nature’s factory, a micro-organism or biologic cell.² The manufacturing process must be nearly identical to that for the reference product, so that only insignificant/nonclinically significant impurities occur in the final product. The protein-amino acid sequence is key and must therefore be identical. The 2010 Biologics Price Competition and Innovation Act established an abbreviated pathway for the FDA to consider and approve biosimilars, and 5 years later, the bone marrow stimulant filgrastim-sndz became the first biosimilar approved for use in the United States.³ The development of biosimilars is not inexpensive. The law and the FDA approval system require preclinical and phase 1 testing, and a robust phase 3 trial against the reference product to demonstrate that safety and efficacy are statistically not different and that any chemical differences between the biosimilar and reference product are clinically and safety or immunogenically insignificant. When those criteria have been met, and the biosimilar approved, the clinical and cost benefits to patients could be significant. In general, the cost of a biosimilar is about 20% to 30% lower than that of the reference product.

Biosimilarity does not yet allow interchangeability. Small-molecule generics under FDA regulations are interchangeable in the drug store and the hospital without the prescriber or patient being aware. That is not yet the case with biosimilars, but their lower prices could have a notable impact on overall cost of care. In 2013, 7 of the top 8 best-selling drugs in the global market were biologics.⁴ Three of the top 8 – rituximab, trastuzumab, and bevacizumab – were used to treat cancer, and 1 (pegfilgrastim) was for therapy-related neutropenia. Their total cost was US$27 billion. Biosimilars of those therapies could significantly lower that amount.

Nabhan and colleagues interviewed 510 US-based community oncologists about their understanding of biosimilars. They found that only 29% of respondents said they prescribed filgrastim-sndz for supportive care by personal choice, but upward of 73% said they would prescribe biosimilars for the active anticancer therapies, trastuzumab and bevacizumab. There’s no question that biosimilars are here to stay. The requirements to make them have been well worked out. Their safety and efficacy therefore can be assured, and their lower prices promise cost savings for patients and society as a whole.

Biosimilars have arrived, and chances are that you’re already prescribing them. Last September, the US Food and Drug Administration (FDA) approved the first cancer-specific biosimilar, bevacizumab-awwb, for multiple cancer types (p. e60);¹ and in November, it approved trastuzumab-dkst for HER2-positive breast and gastrointestinal cancers (p. e63).¹ Briefly, biosimilars are biologic products that show comparable quality, efficacy, and safety to an existing, approved biologic known as the reference product.

Small-molecule drugs such as aspirin are easy to replicate identically, whereas biosimilars are large, complex proteins that are manufactured in nature’s factory, a micro-organism or biologic cell.² The manufacturing process must be nearly identical to that for the reference product, so that only insignificant/nonclinically significant impurities occur in the final product. The protein-amino acid sequence is key and must therefore be identical. The 2010 Biologics Price Competition and Innovation Act established an abbreviated pathway for the FDA to consider and approve biosimilars, and 5 years later, the bone marrow stimulant filgrastim-sndz became the first biosimilar approved for use in the United States.³ The development of biosimilars is not inexpensive. The law and the FDA approval system require preclinical and phase 1 testing, and a robust phase 3 trial against the reference product to demonstrate that safety and efficacy are statistically not different and that any chemical differences between the biosimilar and reference product are clinically and safety or immunogenically insignificant. When those criteria have been met, and the biosimilar approved, the clinical and cost benefits to patients could be significant. In general, the cost of a biosimilar is about 20% to 30% lower than that of the reference product.

Biosimilarity does not yet allow interchangeability. Small-molecule generics under FDA regulations are interchangeable in the drug store and the hospital without the prescriber or patient being aware. That is not yet the case with biosimilars, but their lower prices could have a notable impact on overall cost of care. In 2013, 7 of the top 8 best-selling drugs in the global market were biologics.⁴ Three of the top 8 – rituximab, trastuzumab, and bevacizumab – were used to treat cancer, and 1 (pegfilgrastim) was for therapy-related neutropenia. Their total cost was US$27 billion. Biosimilars of those therapies could significantly lower that amount.

Nabhan and colleagues interviewed 510 US-based community oncologists about their understanding of biosimilars. They found that only 29% of respondents said they prescribed filgrastim-sndz for supportive care by personal choice, but upward of 73% said they would prescribe biosimilars for the active anticancer therapies, trastuzumab and bevacizumab. There’s no question that biosimilars are here to stay. The requirements to make them have been well worked out. Their safety and efficacy therefore can be assured, and their lower prices promise cost savings for patients and society as a whole.

Biosimilars have arrived, and chances are that you’re already prescribing them. Last September, the US Food and Drug Administration (FDA) approved the first cancer-specific biosimilar, bevacizumab-awwb, for multiple cancer types (p. e60);¹ and in November, it approved trastuzumab-dkst for HER2-positive breast and gastrointestinal cancers (p. e63).¹ Briefly, biosimilars are biologic products that show comparable quality, efficacy, and safety to an existing, approved biologic known as the reference product.

Small-molecule drugs such as aspirin are easy to replicate identically, whereas biosimilars are large, complex proteins that are manufactured in nature’s factory, a micro-organism or biologic cell.² The manufacturing process must be nearly identical to that for the reference product, so that only insignificant/nonclinically significant impurities occur in the final product. The protein-amino acid sequence is key and must therefore be identical. The 2010 Biologics Price Competition and Innovation Act established an abbreviated pathway for the FDA to consider and approve biosimilars, and 5 years later, the bone marrow stimulant filgrastim-sndz became the first biosimilar approved for use in the United States.³ The development of biosimilars is not inexpensive. The law and the FDA approval system require preclinical and phase 1 testing, and a robust phase 3 trial against the reference product to demonstrate that safety and efficacy are statistically not different and that any chemical differences between the biosimilar and reference product are clinically and safety or immunogenically insignificant. When those criteria have been met, and the biosimilar approved, the clinical and cost benefits to patients could be significant. In general, the cost of a biosimilar is about 20% to 30% lower than that of the reference product.

Biosimilarity does not yet allow interchangeability. Small-molecule generics under FDA regulations are interchangeable in the drug store and the hospital without the prescriber or patient being aware. That is not yet the case with biosimilars, but their lower prices could have a notable impact on overall cost of care. In 2013, 7 of the top 8 best-selling drugs in the global market were biologics.⁴ Three of the top 8 – rituximab, trastuzumab, and bevacizumab – were used to treat cancer, and 1 (pegfilgrastim) was for therapy-related neutropenia. Their total cost was US$27 billion. Biosimilars of those therapies could significantly lower that amount.

Nabhan and colleagues interviewed 510 US-based community oncologists about their understanding of biosimilars. They found that only 29% of respondents said they prescribed filgrastim-sndz for supportive care by personal choice, but upward of 73% said they would prescribe biosimilars for the active anticancer therapies, trastuzumab and bevacizumab. There’s no question that biosimilars are here to stay. The requirements to make them have been well worked out. Their safety and efficacy therefore can be assured, and their lower prices promise cost savings for patients and society as a whole.

Non–small cell lung cancer constitutes 80%-85% of lung cancers, and 40% of NSCLC are adenocarcinoma. It is rare to find intraocular metastasis from lung cancer. In this article, we present the case of a patient who presented with complaints of diminished vision redness of the eye and was found to have intra-ocular metastases from lung cancer.

Case presentation and summary

A 60-year-old man with a 40-pack per year history of smoking presented to multiple ophthalmologists with complaints of decreased vision and redness of the left eye. He was eventually evaluated by an ophthalmologist who performed a biopsy of the anterior chamber of the eye. Histologic findings were consistent with adenocarcinoma of lung primary (Figures 1 and 2).

After the diagnosis, a chest X-ray showed that the patient had a left lower lung mass. The results of his physical exam were all within normal limits, with the exception of decreased visual acuity in the left eye. The results of his laboratory studies, including complete blood count and serum chemistries, were also within normal limits. Imaging studies – including a computed-tomography (CT) scan of the chest, abdomen, and pelvis and a full-body positron-emission tomography–CT scan – showed a hypermetabolic left lower lobe mass 4.5 cm and right lower paratracheal lymph node metastasis 2 cm with a small focus of increased uptake alone the medial aspect of the left globe (Figures 3 and 4).

An MRI orbit was performed in an attempt to better characterize the left eye mass, but no optic lesion was identified. A biopsy of the left lower lung mass was consistent with non–small-cell lung cancer (NSCLC). Aside from the isolated left eye metastases, the patient did not have evidence of other distant metastatic involvement.

Discussion

Choroidal metastasis is the most common site of intraocular tumor. In an autopsy study of 230 patients with carcinoma, 12% of cases demonstrated histologic evidence of ocular metastasis.¹ A retrospective series of patients with malignant involvement of the eye, 66% of patients had a known history of primary cancer and in 34% of patients the ocular tumor was the first sign of cancer.² The most common cancers that were found to have ocular metastasis were lung and breast cancer.² Adenocarcinoma was the most common histologic type of lung cancer to result in ocular metastases and was seen in 41% of patients.³

Decreased or blurred vision with redness as the primary complaint of NSCLC is rare. Only a few case reports are available. Abundo and colleagues reported that 0.7%-12% of patients with lung cancer develop ocular metastases.⁴ Therefore, routine ophthalmologic screening for ocular metastases in patients with cancer has not been pursued in asymptomatic patients.⁵ Ophthalmological evaluation is recommended in symptomatic patients.

Metastatic involvement of two or more other organs was found to be a risk factor for development of choroidal metastasis in patients with lung cancer though in our patient no evidence of other organ involvement was found.⁵ The most common site of metastases in patients with NSCLC with ocular metastases was found to be the liver. Choroidal metastases was reported to be the sixth common site of metastases in patients with lung cancer.⁵

Treatment of ocular manifestations has been generally confined to surgical resection or radiation therapy, but advances in chemotherapy and development of novel targeted agents have shown promising results.⁷ Median life expectancy after a diagnosis of uveal metastases was reported to be 12 months in a retrospective study, which is similar to the reported median survival in metastatic NSCLC.⁸

Our patient was enrolled in a clinical trial and was treated with a regimen of carboplatin, paclitaxel, and bevacizumab. On presentation, he had significant impairment of vision with pain. He was treated with intravitreal bevacizumab yielding improvement in his visual symptoms. Bevacizumab is a vascular endothelial growth factor receptor monoclonal antibody approved for use in patients with metastatic lung cancer. Other pathways that have been reported in development of lung cancer involve the ALK gene translocation, and EGFR and K-RAS mutations, and targeted therapy has shown good results in cancer patients with these molecular defects. Randomized clinical trials in patients with advanced NSCLC and an EGFR mutation have shown significant improvement in overall survival with the use of erlotinib, a tyrosine kinase inhibitor targeting the epidermal growth factor receptor.⁹ Similarly, crizotinib has shown promising results in patients with metastatic NSCLC who have ELM-ALK rearrangement.¹⁰ As our patient’s tumor did not have either of these mutations, he was initiated on chemotherapy with bevacizumab. The presence of a K-RAS mutation in this patient further supported the use of front-line chemotherapy given that it may confer resistance against agents that target the EGFR pathway.

In our review of the literature, we found cases of patients with ocular metastases who responded well to therapy with targeted agents (Table).

Conclusion

The goal of therapy in metastatic lung cancer is palliation of symptoms and improvement in patient quality of life with prolongation in overall survival. The newer targeted chemotherapeutic agents assist in achieving these goals and may decrease the morbidity associated from radiation or surgery with improvement in vision and regression of ocular metastatic lesions. Targeted therapies should be considered in the treatment of patients with ocular metastases from NSCLC.

Non–small cell lung cancer constitutes 80%-85% of lung cancers, and 40% of NSCLC are adenocarcinoma. It is rare to find intraocular metastasis from lung cancer. In this article, we present the case of a patient who presented with complaints of diminished vision redness of the eye and was found to have intra-ocular metastases from lung cancer.

Case presentation and summary

A 60-year-old man with a 40-pack per year history of smoking presented to multiple ophthalmologists with complaints of decreased vision and redness of the left eye. He was eventually evaluated by an ophthalmologist who performed a biopsy of the anterior chamber of the eye. Histologic findings were consistent with adenocarcinoma of lung primary (Figures 1 and 2).

After the diagnosis, a chest X-ray showed that the patient had a left lower lung mass. The results of his physical exam were all within normal limits, with the exception of decreased visual acuity in the left eye. The results of his laboratory studies, including complete blood count and serum chemistries, were also within normal limits. Imaging studies – including a computed-tomography (CT) scan of the chest, abdomen, and pelvis and a full-body positron-emission tomography–CT scan – showed a hypermetabolic left lower lobe mass 4.5 cm and right lower paratracheal lymph node metastasis 2 cm with a small focus of increased uptake alone the medial aspect of the left globe (Figures 3 and 4).

An MRI orbit was performed in an attempt to better characterize the left eye mass, but no optic lesion was identified. A biopsy of the left lower lung mass was consistent with non–small-cell lung cancer (NSCLC). Aside from the isolated left eye metastases, the patient did not have evidence of other distant metastatic involvement.

Discussion

Choroidal metastasis is the most common site of intraocular tumor. In an autopsy study of 230 patients with carcinoma, 12% of cases demonstrated histologic evidence of ocular metastasis.¹ A retrospective series of patients with malignant involvement of the eye, 66% of patients had a known history of primary cancer and in 34% of patients the ocular tumor was the first sign of cancer.² The most common cancers that were found to have ocular metastasis were lung and breast cancer.² Adenocarcinoma was the most common histologic type of lung cancer to result in ocular metastases and was seen in 41% of patients.³

Decreased or blurred vision with redness as the primary complaint of NSCLC is rare. Only a few case reports are available. Abundo and colleagues reported that 0.7%-12% of patients with lung cancer develop ocular metastases.⁴ Therefore, routine ophthalmologic screening for ocular metastases in patients with cancer has not been pursued in asymptomatic patients.⁵ Ophthalmological evaluation is recommended in symptomatic patients.

Metastatic involvement of two or more other organs was found to be a risk factor for development of choroidal metastasis in patients with lung cancer though in our patient no evidence of other organ involvement was found.⁵ The most common site of metastases in patients with NSCLC with ocular metastases was found to be the liver. Choroidal metastases was reported to be the sixth common site of metastases in patients with lung cancer.⁵

Treatment of ocular manifestations has been generally confined to surgical resection or radiation therapy, but advances in chemotherapy and development of novel targeted agents have shown promising results.⁷ Median life expectancy after a diagnosis of uveal metastases was reported to be 12 months in a retrospective study, which is similar to the reported median survival in metastatic NSCLC.⁸

Our patient was enrolled in a clinical trial and was treated with a regimen of carboplatin, paclitaxel, and bevacizumab. On presentation, he had significant impairment of vision with pain. He was treated with intravitreal bevacizumab yielding improvement in his visual symptoms. Bevacizumab is a vascular endothelial growth factor receptor monoclonal antibody approved for use in patients with metastatic lung cancer. Other pathways that have been reported in development of lung cancer involve the ALK gene translocation, and EGFR and K-RAS mutations, and targeted therapy has shown good results in cancer patients with these molecular defects. Randomized clinical trials in patients with advanced NSCLC and an EGFR mutation have shown significant improvement in overall survival with the use of erlotinib, a tyrosine kinase inhibitor targeting the epidermal growth factor receptor.⁹ Similarly, crizotinib has shown promising results in patients with metastatic NSCLC who have ELM-ALK rearrangement.¹⁰ As our patient’s tumor did not have either of these mutations, he was initiated on chemotherapy with bevacizumab. The presence of a K-RAS mutation in this patient further supported the use of front-line chemotherapy given that it may confer resistance against agents that target the EGFR pathway.

In our review of the literature, we found cases of patients with ocular metastases who responded well to therapy with targeted agents (Table).

Conclusion

The goal of therapy in metastatic lung cancer is palliation of symptoms and improvement in patient quality of life with prolongation in overall survival. The newer targeted chemotherapeutic agents assist in achieving these goals and may decrease the morbidity associated from radiation or surgery with improvement in vision and regression of ocular metastatic lesions. Targeted therapies should be considered in the treatment of patients with ocular metastases from NSCLC.

Non–small cell lung cancer constitutes 80%-85% of lung cancers, and 40% of NSCLC are adenocarcinoma. It is rare to find intraocular metastasis from lung cancer. In this article, we present the case of a patient who presented with complaints of diminished vision redness of the eye and was found to have intra-ocular metastases from lung cancer.

Case presentation and summary

A 60-year-old man with a 40-pack per year history of smoking presented to multiple ophthalmologists with complaints of decreased vision and redness of the left eye. He was eventually evaluated by an ophthalmologist who performed a biopsy of the anterior chamber of the eye. Histologic findings were consistent with adenocarcinoma of lung primary (Figures 1 and 2).

After the diagnosis, a chest X-ray showed that the patient had a left lower lung mass. The results of his physical exam were all within normal limits, with the exception of decreased visual acuity in the left eye. The results of his laboratory studies, including complete blood count and serum chemistries, were also within normal limits. Imaging studies – including a computed-tomography (CT) scan of the chest, abdomen, and pelvis and a full-body positron-emission tomography–CT scan – showed a hypermetabolic left lower lobe mass 4.5 cm and right lower paratracheal lymph node metastasis 2 cm with a small focus of increased uptake alone the medial aspect of the left globe (Figures 3 and 4).

An MRI orbit was performed in an attempt to better characterize the left eye mass, but no optic lesion was identified. A biopsy of the left lower lung mass was consistent with non–small-cell lung cancer (NSCLC). Aside from the isolated left eye metastases, the patient did not have evidence of other distant metastatic involvement.

Discussion

Choroidal metastasis is the most common site of intraocular tumor. In an autopsy study of 230 patients with carcinoma, 12% of cases demonstrated histologic evidence of ocular metastasis.¹ A retrospective series of patients with malignant involvement of the eye, 66% of patients had a known history of primary cancer and in 34% of patients the ocular tumor was the first sign of cancer.² The most common cancers that were found to have ocular metastasis were lung and breast cancer.² Adenocarcinoma was the most common histologic type of lung cancer to result in ocular metastases and was seen in 41% of patients.³

Decreased or blurred vision with redness as the primary complaint of NSCLC is rare. Only a few case reports are available. Abundo and colleagues reported that 0.7%-12% of patients with lung cancer develop ocular metastases.⁴ Therefore, routine ophthalmologic screening for ocular metastases in patients with cancer has not been pursued in asymptomatic patients.⁵ Ophthalmological evaluation is recommended in symptomatic patients.

Metastatic involvement of two or more other organs was found to be a risk factor for development of choroidal metastasis in patients with lung cancer though in our patient no evidence of other organ involvement was found.⁵ The most common site of metastases in patients with NSCLC with ocular metastases was found to be the liver. Choroidal metastases was reported to be the sixth common site of metastases in patients with lung cancer.⁵

Treatment of ocular manifestations has been generally confined to surgical resection or radiation therapy, but advances in chemotherapy and development of novel targeted agents have shown promising results.⁷ Median life expectancy after a diagnosis of uveal metastases was reported to be 12 months in a retrospective study, which is similar to the reported median survival in metastatic NSCLC.⁸

Our patient was enrolled in a clinical trial and was treated with a regimen of carboplatin, paclitaxel, and bevacizumab. On presentation, he had significant impairment of vision with pain. He was treated with intravitreal bevacizumab yielding improvement in his visual symptoms. Bevacizumab is a vascular endothelial growth factor receptor monoclonal antibody approved for use in patients with metastatic lung cancer. Other pathways that have been reported in development of lung cancer involve the ALK gene translocation, and EGFR and K-RAS mutations, and targeted therapy has shown good results in cancer patients with these molecular defects. Randomized clinical trials in patients with advanced NSCLC and an EGFR mutation have shown significant improvement in overall survival with the use of erlotinib, a tyrosine kinase inhibitor targeting the epidermal growth factor receptor.⁹ Similarly, crizotinib has shown promising results in patients with metastatic NSCLC who have ELM-ALK rearrangement.¹⁰ As our patient’s tumor did not have either of these mutations, he was initiated on chemotherapy with bevacizumab. The presence of a K-RAS mutation in this patient further supported the use of front-line chemotherapy given that it may confer resistance against agents that target the EGFR pathway.

In our review of the literature, we found cases of patients with ocular metastases who responded well to therapy with targeted agents (Table).

Conclusion

The goal of therapy in metastatic lung cancer is palliation of symptoms and improvement in patient quality of life with prolongation in overall survival. The newer targeted chemotherapeutic agents assist in achieving these goals and may decrease the morbidity associated from radiation or surgery with improvement in vision and regression of ocular metastatic lesions. Targeted therapies should be considered in the treatment of patients with ocular metastases from NSCLC.

Substance P is an important neurotransmitter implicated in itch pathways.¹ After binding to its receptor, neurokinin-1 (NK-1), substance P induces release of factors including histamine, which may cause pruritus.² Recent literature has reported successful use of aprepitant, an NK-1 antagonist that has been approved by the US Food and Drug Administration for the treatment of chemotherapy-induced nausea and vomiting, for treatment of pruritus. We report here the case of a patient with microcystic adnexal carcinoma (MAC) who presented with refractory pruritus and who had rapid and complete resolution of itch after administration of aprepitant.

Case presentation and summary

A 73-year-old man presented with a 12-year history of a small nodule on his philtrum, which had been increasing in size. He subsequently developed upper-lip numbness and nasal induration. He complained of 2.5 months of severe, debilitating, full-body pruritus. His symptoms were refractory to treatment with prednisone, gabapentin, doxycycline, doxepin, antihistamines, and topical steroids. At the time of consultation, he was being treated with hydroxyzine and topical pramocaine lotion with minimal relief.

At initial dermatologic evaluation, his tumor involved the lower two-thirds of the nose and entire upper cutaneous lip. There was a 4-mm rolled ulcer on the nasal tip and a 1-cm exophytic, smooth nodule on the left upper lip with palpable 4-cm submandibular adenopathy (Figure). Skin examination otherwise revealed linear excoriations on the upper back with no additional primary lesions. The nodule was biopsied, and the patient was diagnosed with MAC with gross nodal involvement. Laboratory findings including serum chemistries, blood urea nitrogen, complete blood cell count, thyroid, and liver function were normal. Positron emission tomography-computed tomography (PET-CT) imaging was negative for distant metastases.

Discussion

MAC is an uncommon cutaneous malignancy of sweat and eccrine gland differentiation. In all, 700 cases of MAC have been described in the literature; a 2008 review estimated the incidence of metastasis at around 2.1%.³ Though metastasis is exceedingly rare, the tumor is locally aggressive and there are reports of invasion into the muscle, perichondrium, periosteum, bone marrow, as well as perineural spaces and vascular adventitia.⁴

The clinical presentation of MAC includes smooth, flesh-colored or yellow papules, nodules, or plaques.³ Patients often present with numbness, paresthesia, and burning in the area of involvement because of neural infiltration with tumor. Despite the rarity of MAC, pruritus has been reported as a presenting symptom in 1 other case in the literature.⁴ Our case represents the first report of MAC presenting with a grossly enlarging centrofacial mass, lymph node involvement, and severe full-body pruritus. Our patient responded completely, and within hours, to treatment with aprepitant after experiencing months of failure with conventional antipruritus treatments and without recurrence in symptoms in more than 2 years of follow-up.

Aprepitant blocks the binding of substance P to its receptor NK-1 and has been approved as an anti-emetic for chemotherapy patients. Substance P has been shown to be important in both nausea and itch pathways. The largest prospective study to date on aprepitant for the indication of pruritus in 45 patients with metastatic solid tumors demonstrated a 91% response rate, defined by >50% reduction in pruritus intensity, and 13% recurrence rate that occurred at a median of 7 weeks after initial treatment.⁵ Aprepitant treatment has been used with success for pruritus associated with both malignant and nonmalignant conditions in at least 74 patients,⁶ among whom the malignant conditions included cutaneous T-cell lymphoma, Hodgkin lymphoma, and metastatic solid tumors.^5-7 Aprepitant has also been used for erlotinib- and nivolumab-induced pruritus in non–small cell lung cancer, which suggests a possible future role for aprepitant in the treatment of pruritus secondary to novel cancer therapies, perhaps including immune checkpoint inhibitors.^8-10

However, despite those reports, and likely owing to the multifactorial nature of pruritus, aprepitant is not unviversally effective. Mechanisms of malignancy-associated itch are yet to be elucidated, and optimal patient selection for aprepitant use needs to be determined. However, our patient’s notable response supports the increasing evidence that substance P is a key mediator of pruritus and that disruption of binding to its receptor may result in significant improvement in symptoms in certain patients. It remains to be seen whether the cell type or the tendency toward neural invasion plays a role. Large, randomized studies are needed to guide patient selection and confirm the findings reported here and in the literature, with careful documentation of and close attention paid to timing of pruritus relief and improvement in patient quality of life. Aprepitant might be an important therapeutic tool for refractory, malignancy-associated pruritus, in which patient quality of life is especially critical.

Acknowledgments

This work was presented at the Multinational Association of Supportive Care and Cancer Meeting, in Miami Florida, June 26-28, 2014. The authors are indebted to Saajar Jadeja for his assistance preparing the manuscript.

Substance P is an important neurotransmitter implicated in itch pathways.¹ After binding to its receptor, neurokinin-1 (NK-1), substance P induces release of factors including histamine, which may cause pruritus.² Recent literature has reported successful use of aprepitant, an NK-1 antagonist that has been approved by the US Food and Drug Administration for the treatment of chemotherapy-induced nausea and vomiting, for treatment of pruritus. We report here the case of a patient with microcystic adnexal carcinoma (MAC) who presented with refractory pruritus and who had rapid and complete resolution of itch after administration of aprepitant.

Case presentation and summary

A 73-year-old man presented with a 12-year history of a small nodule on his philtrum, which had been increasing in size. He subsequently developed upper-lip numbness and nasal induration. He complained of 2.5 months of severe, debilitating, full-body pruritus. His symptoms were refractory to treatment with prednisone, gabapentin, doxycycline, doxepin, antihistamines, and topical steroids. At the time of consultation, he was being treated with hydroxyzine and topical pramocaine lotion with minimal relief.

At initial dermatologic evaluation, his tumor involved the lower two-thirds of the nose and entire upper cutaneous lip. There was a 4-mm rolled ulcer on the nasal tip and a 1-cm exophytic, smooth nodule on the left upper lip with palpable 4-cm submandibular adenopathy (Figure). Skin examination otherwise revealed linear excoriations on the upper back with no additional primary lesions. The nodule was biopsied, and the patient was diagnosed with MAC with gross nodal involvement. Laboratory findings including serum chemistries, blood urea nitrogen, complete blood cell count, thyroid, and liver function were normal. Positron emission tomography-computed tomography (PET-CT) imaging was negative for distant metastases.

Discussion

MAC is an uncommon cutaneous malignancy of sweat and eccrine gland differentiation. In all, 700 cases of MAC have been described in the literature; a 2008 review estimated the incidence of metastasis at around 2.1%.³ Though metastasis is exceedingly rare, the tumor is locally aggressive and there are reports of invasion into the muscle, perichondrium, periosteum, bone marrow, as well as perineural spaces and vascular adventitia.⁴

The clinical presentation of MAC includes smooth, flesh-colored or yellow papules, nodules, or plaques.³ Patients often present with numbness, paresthesia, and burning in the area of involvement because of neural infiltration with tumor. Despite the rarity of MAC, pruritus has been reported as a presenting symptom in 1 other case in the literature.⁴ Our case represents the first report of MAC presenting with a grossly enlarging centrofacial mass, lymph node involvement, and severe full-body pruritus. Our patient responded completely, and within hours, to treatment with aprepitant after experiencing months of failure with conventional antipruritus treatments and without recurrence in symptoms in more than 2 years of follow-up.

Aprepitant blocks the binding of substance P to its receptor NK-1 and has been approved as an anti-emetic for chemotherapy patients. Substance P has been shown to be important in both nausea and itch pathways. The largest prospective study to date on aprepitant for the indication of pruritus in 45 patients with metastatic solid tumors demonstrated a 91% response rate, defined by >50% reduction in pruritus intensity, and 13% recurrence rate that occurred at a median of 7 weeks after initial treatment.⁵ Aprepitant treatment has been used with success for pruritus associated with both malignant and nonmalignant conditions in at least 74 patients,⁶ among whom the malignant conditions included cutaneous T-cell lymphoma, Hodgkin lymphoma, and metastatic solid tumors.^5-7 Aprepitant has also been used for erlotinib- and nivolumab-induced pruritus in non–small cell lung cancer, which suggests a possible future role for aprepitant in the treatment of pruritus secondary to novel cancer therapies, perhaps including immune checkpoint inhibitors.^8-10

However, despite those reports, and likely owing to the multifactorial nature of pruritus, aprepitant is not unviversally effective. Mechanisms of malignancy-associated itch are yet to be elucidated, and optimal patient selection for aprepitant use needs to be determined. However, our patient’s notable response supports the increasing evidence that substance P is a key mediator of pruritus and that disruption of binding to its receptor may result in significant improvement in symptoms in certain patients. It remains to be seen whether the cell type or the tendency toward neural invasion plays a role. Large, randomized studies are needed to guide patient selection and confirm the findings reported here and in the literature, with careful documentation of and close attention paid to timing of pruritus relief and improvement in patient quality of life. Aprepitant might be an important therapeutic tool for refractory, malignancy-associated pruritus, in which patient quality of life is especially critical.

Acknowledgments

This work was presented at the Multinational Association of Supportive Care and Cancer Meeting, in Miami Florida, June 26-28, 2014. The authors are indebted to Saajar Jadeja for his assistance preparing the manuscript.

Substance P is an important neurotransmitter implicated in itch pathways.¹ After binding to its receptor, neurokinin-1 (NK-1), substance P induces release of factors including histamine, which may cause pruritus.² Recent literature has reported successful use of aprepitant, an NK-1 antagonist that has been approved by the US Food and Drug Administration for the treatment of chemotherapy-induced nausea and vomiting, for treatment of pruritus. We report here the case of a patient with microcystic adnexal carcinoma (MAC) who presented with refractory pruritus and who had rapid and complete resolution of itch after administration of aprepitant.

Case presentation and summary

A 73-year-old man presented with a 12-year history of a small nodule on his philtrum, which had been increasing in size. He subsequently developed upper-lip numbness and nasal induration. He complained of 2.5 months of severe, debilitating, full-body pruritus. His symptoms were refractory to treatment with prednisone, gabapentin, doxycycline, doxepin, antihistamines, and topical steroids. At the time of consultation, he was being treated with hydroxyzine and topical pramocaine lotion with minimal relief.

At initial dermatologic evaluation, his tumor involved the lower two-thirds of the nose and entire upper cutaneous lip. There was a 4-mm rolled ulcer on the nasal tip and a 1-cm exophytic, smooth nodule on the left upper lip with palpable 4-cm submandibular adenopathy (Figure). Skin examination otherwise revealed linear excoriations on the upper back with no additional primary lesions. The nodule was biopsied, and the patient was diagnosed with MAC with gross nodal involvement. Laboratory findings including serum chemistries, blood urea nitrogen, complete blood cell count, thyroid, and liver function were normal. Positron emission tomography-computed tomography (PET-CT) imaging was negative for distant metastases.

Discussion

MAC is an uncommon cutaneous malignancy of sweat and eccrine gland differentiation. In all, 700 cases of MAC have been described in the literature; a 2008 review estimated the incidence of metastasis at around 2.1%.³ Though metastasis is exceedingly rare, the tumor is locally aggressive and there are reports of invasion into the muscle, perichondrium, periosteum, bone marrow, as well as perineural spaces and vascular adventitia.⁴

The clinical presentation of MAC includes smooth, flesh-colored or yellow papules, nodules, or plaques.³ Patients often present with numbness, paresthesia, and burning in the area of involvement because of neural infiltration with tumor. Despite the rarity of MAC, pruritus has been reported as a presenting symptom in 1 other case in the literature.⁴ Our case represents the first report of MAC presenting with a grossly enlarging centrofacial mass, lymph node involvement, and severe full-body pruritus. Our patient responded completely, and within hours, to treatment with aprepitant after experiencing months of failure with conventional antipruritus treatments and without recurrence in symptoms in more than 2 years of follow-up.

Aprepitant blocks the binding of substance P to its receptor NK-1 and has been approved as an anti-emetic for chemotherapy patients. Substance P has been shown to be important in both nausea and itch pathways. The largest prospective study to date on aprepitant for the indication of pruritus in 45 patients with metastatic solid tumors demonstrated a 91% response rate, defined by >50% reduction in pruritus intensity, and 13% recurrence rate that occurred at a median of 7 weeks after initial treatment.⁵ Aprepitant treatment has been used with success for pruritus associated with both malignant and nonmalignant conditions in at least 74 patients,⁶ among whom the malignant conditions included cutaneous T-cell lymphoma, Hodgkin lymphoma, and metastatic solid tumors.^5-7 Aprepitant has also been used for erlotinib- and nivolumab-induced pruritus in non–small cell lung cancer, which suggests a possible future role for aprepitant in the treatment of pruritus secondary to novel cancer therapies, perhaps including immune checkpoint inhibitors.^8-10

However, despite those reports, and likely owing to the multifactorial nature of pruritus, aprepitant is not unviversally effective. Mechanisms of malignancy-associated itch are yet to be elucidated, and optimal patient selection for aprepitant use needs to be determined. However, our patient’s notable response supports the increasing evidence that substance P is a key mediator of pruritus and that disruption of binding to its receptor may result in significant improvement in symptoms in certain patients. It remains to be seen whether the cell type or the tendency toward neural invasion plays a role. Large, randomized studies are needed to guide patient selection and confirm the findings reported here and in the literature, with careful documentation of and close attention paid to timing of pruritus relief and improvement in patient quality of life. Aprepitant might be an important therapeutic tool for refractory, malignancy-associated pruritus, in which patient quality of life is especially critical.

Acknowledgments

This work was presented at the Multinational Association of Supportive Care and Cancer Meeting, in Miami Florida, June 26-28, 2014. The authors are indebted to Saajar Jadeja for his assistance preparing the manuscript.

AUSTIN, TEXAS – When the check box for ordering formula for newborns was removed as a standard newborn order option in the electronic health record (EHR), rates of exclusive breastfeeding climbed significantly in Los Angeles County hospitals, according to a recent study.

“The saying, ‘out of sight, out of mind’ cannot be overstated when it comes to physician order entry,” wrote Ramy Eskander, MD, and his colleagues in the poster accompanying the presentation at the annual clinical and scientific sessions of the American College of Obstetricians and Gynecologists.

In a video interview, Dr. Eskander said that he and his colleagues at the University of California, Los Angeles, were looking for an intervention that would use the EHR as a quality improvement tool.

What they decided to do was to see “how could we possibly ‘get in the way’ and have an intervention between the provider and the patient that didn’t necessarily involve much work on the provider’s end, that had a significant impact on the back end,” he said. What they ended up doing was remove the order to request formula for mothers from the physician order set in the EHR.

Study data were collected in three stages for the academic tertiary care hospital within the Los Angeles County Department of Health Services system.

First, Dr. Eskander and his colleagues collected baseline data from January to July of 2016. Then, data were collected from July to the end of 2016, while a campaign was underway to bring staff and patients up to speed on the benefits of exclusive breastfeeding. There were no statistically significant differences in the rates of exclusive breastfeeding on discharge between these two time periods, when rates hovered between 30% and 40%.

The final data collection period began in January 2017. At that time, the option to order formula for a newborn was removed as an option for the EHR newborn order set.

“When we did that, providers weren’t looking at the possibility of having that easy check box right there to fill in … and we know that when people have to go through more steps, they invariably don’t do it,” Dr. Eskander said.

He and his colleagues saw an almost immediate leap in rates of exclusive breastfeeding once clinicians had to click through an additional set of screens to reach the formula order. Once the formula order was removed, breastfeeding rates rose from 40.57% to 53.90% (P less than .001). Rates have been sustained since the removal of the EHR option for formula.

There was no difference in how infants fared after the intervention, said Dr. Eskander. “The outcomes for those infants was identical. There were no increased NICU admissions, there were no increased poor outcomes.”

Length of stay remained the same as well. “The babies were being discharged in the same state of health, just more of them were getting breast milk only, and we know the benefits that tends to portend,” he added.

There was some initial grumbling when the formula order was pulled from the newborn order set, he conceded. “The providers were not very happy about having to look for the newborn order for formula.” However, it took just about a month for the new workflow to seem normal, he said.

Dr. Eskander envisions a future where the EHR is “smart” enough to prompt appropriate orders and interventions for serious conditions such as preeclampsia. The electronic record, he said, could recognize the maternal diagnosis “and immediately create a system and structure around that mother to be able to help protect her and her baby. ... then having those diagnoses be able to drive outcomes can be very significant.”

Dr. Eskander reported no relevant financial disclosures.

[email protected]

SOURCE: Eskander, R et al. ACOG 2018, Abstract 31I.

AUSTIN, TEXAS – When the check box for ordering formula for newborns was removed as a standard newborn order option in the electronic health record (EHR), rates of exclusive breastfeeding climbed significantly in Los Angeles County hospitals, according to a recent study.

“The saying, ‘out of sight, out of mind’ cannot be overstated when it comes to physician order entry,” wrote Ramy Eskander, MD, and his colleagues in the poster accompanying the presentation at the annual clinical and scientific sessions of the American College of Obstetricians and Gynecologists.

In a video interview, Dr. Eskander said that he and his colleagues at the University of California, Los Angeles, were looking for an intervention that would use the EHR as a quality improvement tool.

What they decided to do was to see “how could we possibly ‘get in the way’ and have an intervention between the provider and the patient that didn’t necessarily involve much work on the provider’s end, that had a significant impact on the back end,” he said. What they ended up doing was remove the order to request formula for mothers from the physician order set in the EHR.

Study data were collected in three stages for the academic tertiary care hospital within the Los Angeles County Department of Health Services system.

First, Dr. Eskander and his colleagues collected baseline data from January to July of 2016. Then, data were collected from July to the end of 2016, while a campaign was underway to bring staff and patients up to speed on the benefits of exclusive breastfeeding. There were no statistically significant differences in the rates of exclusive breastfeeding on discharge between these two time periods, when rates hovered between 30% and 40%.

The final data collection period began in January 2017. At that time, the option to order formula for a newborn was removed as an option for the EHR newborn order set.

“When we did that, providers weren’t looking at the possibility of having that easy check box right there to fill in … and we know that when people have to go through more steps, they invariably don’t do it,” Dr. Eskander said.

He and his colleagues saw an almost immediate leap in rates of exclusive breastfeeding once clinicians had to click through an additional set of screens to reach the formula order. Once the formula order was removed, breastfeeding rates rose from 40.57% to 53.90% (P less than .001). Rates have been sustained since the removal of the EHR option for formula.

There was no difference in how infants fared after the intervention, said Dr. Eskander. “The outcomes for those infants was identical. There were no increased NICU admissions, there were no increased poor outcomes.”

Length of stay remained the same as well. “The babies were being discharged in the same state of health, just more of them were getting breast milk only, and we know the benefits that tends to portend,” he added.

There was some initial grumbling when the formula order was pulled from the newborn order set, he conceded. “The providers were not very happy about having to look for the newborn order for formula.” However, it took just about a month for the new workflow to seem normal, he said.

Dr. Eskander envisions a future where the EHR is “smart” enough to prompt appropriate orders and interventions for serious conditions such as preeclampsia. The electronic record, he said, could recognize the maternal diagnosis “and immediately create a system and structure around that mother to be able to help protect her and her baby. ... then having those diagnoses be able to drive outcomes can be very significant.”

Dr. Eskander reported no relevant financial disclosures.

[email protected]

SOURCE: Eskander, R et al. ACOG 2018, Abstract 31I.

AUSTIN, TEXAS – When the check box for ordering formula for newborns was removed as a standard newborn order option in the electronic health record (EHR), rates of exclusive breastfeeding climbed significantly in Los Angeles County hospitals, according to a recent study.

“The saying, ‘out of sight, out of mind’ cannot be overstated when it comes to physician order entry,” wrote Ramy Eskander, MD, and his colleagues in the poster accompanying the presentation at the annual clinical and scientific sessions of the American College of Obstetricians and Gynecologists.

In a video interview, Dr. Eskander said that he and his colleagues at the University of California, Los Angeles, were looking for an intervention that would use the EHR as a quality improvement tool.

What they decided to do was to see “how could we possibly ‘get in the way’ and have an intervention between the provider and the patient that didn’t necessarily involve much work on the provider’s end, that had a significant impact on the back end,” he said. What they ended up doing was remove the order to request formula for mothers from the physician order set in the EHR.

Study data were collected in three stages for the academic tertiary care hospital within the Los Angeles County Department of Health Services system.

First, Dr. Eskander and his colleagues collected baseline data from January to July of 2016. Then, data were collected from July to the end of 2016, while a campaign was underway to bring staff and patients up to speed on the benefits of exclusive breastfeeding. There were no statistically significant differences in the rates of exclusive breastfeeding on discharge between these two time periods, when rates hovered between 30% and 40%.

The final data collection period began in January 2017. At that time, the option to order formula for a newborn was removed as an option for the EHR newborn order set.

“When we did that, providers weren’t looking at the possibility of having that easy check box right there to fill in … and we know that when people have to go through more steps, they invariably don’t do it,” Dr. Eskander said.

He and his colleagues saw an almost immediate leap in rates of exclusive breastfeeding once clinicians had to click through an additional set of screens to reach the formula order. Once the formula order was removed, breastfeeding rates rose from 40.57% to 53.90% (P less than .001). Rates have been sustained since the removal of the EHR option for formula.

There was no difference in how infants fared after the intervention, said Dr. Eskander. “The outcomes for those infants was identical. There were no increased NICU admissions, there were no increased poor outcomes.”

Length of stay remained the same as well. “The babies were being discharged in the same state of health, just more of them were getting breast milk only, and we know the benefits that tends to portend,” he added.

There was some initial grumbling when the formula order was pulled from the newborn order set, he conceded. “The providers were not very happy about having to look for the newborn order for formula.” However, it took just about a month for the new workflow to seem normal, he said.

Dr. Eskander envisions a future where the EHR is “smart” enough to prompt appropriate orders and interventions for serious conditions such as preeclampsia. The electronic record, he said, could recognize the maternal diagnosis “and immediately create a system and structure around that mother to be able to help protect her and her baby. ... then having those diagnoses be able to drive outcomes can be very significant.”

Dr. Eskander reported no relevant financial disclosures.

[email protected]

SOURCE: Eskander, R et al. ACOG 2018, Abstract 31I.

LIVERPOOL, ENGLAND – Decades after they were sustained, acute knee injuries caused clinically significant impairments in patient-reported outcomes, as well as upped the risk for knee osteoarthritis (OA) in an observational study.

Results of the study, which followed up individuals 32-37 years after they were treated for a ruptured anterior cruciate ligament (ACL) injury between 1980 and 1985, showed that, compared with the general population, they experienced greater levels of knee pain, participated less in physical activities, and had a reduced quality of life.

Sara Freeman/MDEdge News

The average age of participants at follow-up was 59 years (range, 47-74 years); 30% were female. 58% of all patients had been treated non-surgically initially, and 38% remained non-surgically treated at the longterm follow-up. At baseline, 58% had a meniscus injury.

Compared with an age- and sex-matched Swedish population, patients with ACL injuries had a lower KOOS for pain, sport/recreational activities, and quality of life. For example, KOOS for knee pain was around 65-70 for those with prior ACL injuries, compared with 80-90 for those without ACL injuries, where 100 indicates the best outcome or least pain and zero the worst.

KOOS was not affected by whether or not patients had initial ACL surgery or surgery at any point in their follow up. It also did not appear to matter if patients had a meniscal injury at baseline or not.

Quadriceps and hamstring strength at the 3-7 year postinjury assessment did not affect the longterm KOOS, but the ability to hop on one leg did: Those who were not able to hop on one leg for more than 90% of the time on the unaffected limb at the 3-7 years follow-up had worse pain, symptoms, function, and quality of life at the longterm follow-up point.

With regards to OA, “overall, more than one in two individuals had Kellgren-Lawrence grade 4 that could be considered severe radiographic changes in at least one compartment,” Dr. Filbay said at the meeting, which is sponsored by the Osteoarthritis Research Society International.

Severe radiographic changes were most common in the tibiofemoral joint, with around 47% having Kellgren-Lawrence (KL) grade 4. About 35% of tibiofemoral joints and about 60% of patellofemoral joints were KL grade 1.

Interestingly, different factors were found to be associated with OA in the tibiofemoral and patellofemoral joints, according to Dr. Filbay. Patients who had been treated non-surgically, whether initially or at any time during the 32-37 year follow-up, were more likely to have tibiofemoral OA, whereas those who had been treated surgically tended to have patellofemoral OA.

“Perhaps not surprisingly, meniscal injury at baseline was related to a higher percentage of tibiofemoral OA at long-term follow-up,” Dr. Filbay said.

Another finding was that patients with weaker hamstrings 3-7 years after the injury were more likely to develop patellofemoral joint OA.

Dr. Filbay had no disclosures.

[email protected]

SOURCE: Filbay S, et al. Osteoarthritis Cartilage 2018:26(1):S52-3. Abstract 80.

LIVERPOOL, ENGLAND – Decades after they were sustained, acute knee injuries caused clinically significant impairments in patient-reported outcomes, as well as upped the risk for knee osteoarthritis (OA) in an observational study.

Results of the study, which followed up individuals 32-37 years after they were treated for a ruptured anterior cruciate ligament (ACL) injury between 1980 and 1985, showed that, compared with the general population, they experienced greater levels of knee pain, participated less in physical activities, and had a reduced quality of life.

Sara Freeman/MDEdge News

The average age of participants at follow-up was 59 years (range, 47-74 years); 30% were female. 58% of all patients had been treated non-surgically initially, and 38% remained non-surgically treated at the longterm follow-up. At baseline, 58% had a meniscus injury.

Compared with an age- and sex-matched Swedish population, patients with ACL injuries had a lower KOOS for pain, sport/recreational activities, and quality of life. For example, KOOS for knee pain was around 65-70 for those with prior ACL injuries, compared with 80-90 for those without ACL injuries, where 100 indicates the best outcome or least pain and zero the worst.

KOOS was not affected by whether or not patients had initial ACL surgery or surgery at any point in their follow up. It also did not appear to matter if patients had a meniscal injury at baseline or not.

Quadriceps and hamstring strength at the 3-7 year postinjury assessment did not affect the longterm KOOS, but the ability to hop on one leg did: Those who were not able to hop on one leg for more than 90% of the time on the unaffected limb at the 3-7 years follow-up had worse pain, symptoms, function, and quality of life at the longterm follow-up point.

With regards to OA, “overall, more than one in two individuals had Kellgren-Lawrence grade 4 that could be considered severe radiographic changes in at least one compartment,” Dr. Filbay said at the meeting, which is sponsored by the Osteoarthritis Research Society International.

Severe radiographic changes were most common in the tibiofemoral joint, with around 47% having Kellgren-Lawrence (KL) grade 4. About 35% of tibiofemoral joints and about 60% of patellofemoral joints were KL grade 1.

Interestingly, different factors were found to be associated with OA in the tibiofemoral and patellofemoral joints, according to Dr. Filbay. Patients who had been treated non-surgically, whether initially or at any time during the 32-37 year follow-up, were more likely to have tibiofemoral OA, whereas those who had been treated surgically tended to have patellofemoral OA.

“Perhaps not surprisingly, meniscal injury at baseline was related to a higher percentage of tibiofemoral OA at long-term follow-up,” Dr. Filbay said.

Another finding was that patients with weaker hamstrings 3-7 years after the injury were more likely to develop patellofemoral joint OA.

Dr. Filbay had no disclosures.

[email protected]

SOURCE: Filbay S, et al. Osteoarthritis Cartilage 2018:26(1):S52-3. Abstract 80.

LIVERPOOL, ENGLAND – Decades after they were sustained, acute knee injuries caused clinically significant impairments in patient-reported outcomes, as well as upped the risk for knee osteoarthritis (OA) in an observational study.

Results of the study, which followed up individuals 32-37 years after they were treated for a ruptured anterior cruciate ligament (ACL) injury between 1980 and 1985, showed that, compared with the general population, they experienced greater levels of knee pain, participated less in physical activities, and had a reduced quality of life.

Sara Freeman/MDEdge News

The average age of participants at follow-up was 59 years (range, 47-74 years); 30% were female. 58% of all patients had been treated non-surgically initially, and 38% remained non-surgically treated at the longterm follow-up. At baseline, 58% had a meniscus injury.

Compared with an age- and sex-matched Swedish population, patients with ACL injuries had a lower KOOS for pain, sport/recreational activities, and quality of life. For example, KOOS for knee pain was around 65-70 for those with prior ACL injuries, compared with 80-90 for those without ACL injuries, where 100 indicates the best outcome or least pain and zero the worst.

KOOS was not affected by whether or not patients had initial ACL surgery or surgery at any point in their follow up. It also did not appear to matter if patients had a meniscal injury at baseline or not.

Quadriceps and hamstring strength at the 3-7 year postinjury assessment did not affect the longterm KOOS, but the ability to hop on one leg did: Those who were not able to hop on one leg for more than 90% of the time on the unaffected limb at the 3-7 years follow-up had worse pain, symptoms, function, and quality of life at the longterm follow-up point.

With regards to OA, “overall, more than one in two individuals had Kellgren-Lawrence grade 4 that could be considered severe radiographic changes in at least one compartment,” Dr. Filbay said at the meeting, which is sponsored by the Osteoarthritis Research Society International.

Severe radiographic changes were most common in the tibiofemoral joint, with around 47% having Kellgren-Lawrence (KL) grade 4. About 35% of tibiofemoral joints and about 60% of patellofemoral joints were KL grade 1.

Interestingly, different factors were found to be associated with OA in the tibiofemoral and patellofemoral joints, according to Dr. Filbay. Patients who had been treated non-surgically, whether initially or at any time during the 32-37 year follow-up, were more likely to have tibiofemoral OA, whereas those who had been treated surgically tended to have patellofemoral OA.

“Perhaps not surprisingly, meniscal injury at baseline was related to a higher percentage of tibiofemoral OA at long-term follow-up,” Dr. Filbay said.

Another finding was that patients with weaker hamstrings 3-7 years after the injury were more likely to develop patellofemoral joint OA.

Dr. Filbay had no disclosures.

[email protected]

SOURCE: Filbay S, et al. Osteoarthritis Cartilage 2018:26(1):S52-3. Abstract 80.

The clinical presentation of bladder cancer typically presents with hematuria; changes in voiding habits such as urgency, frequency, and pain; or less commonly, obstructive symptoms. Rarely does bladder cancer first present as part of a paraneoplastic syndrome with an inflammatory myopathy. Inflammatory myopathies such as dermatomyositis have been known to be associated with malignancy, however, in a meta-analysis by Yang and colleagues of 449 patients with dermatomyositis and malignancy there were only 8 cases reported of bladder cancer.¹ Herein, we report a paraneoplastic dermatomyositis in the setting of a bladder cancer.

Case presentation and summary

A 65-year-old man with a medical history of hypertension and alcohol use presented to the emergency department with worsening pain, stiffness in the neck, shoulders, and inability to lift his arms above his shoulders. During the physical exam, an erythematous purple rash was noted over his chest, neck, and arms. Upon further evaluation, his creatine phosphokinase was 3,500 U/L (reference range 52-336 U/L) suggesting muscle breakdown and possible inflammatory myopathy. A biopsy of the left deltoid and quadriceps muscles was performed and yielded a diagnosis of dermatomyositis. He was treated with prednisone 60 mg daily for his inflammatory myopathy. The patient also reported an unintentional weight loss of 20 lbs. and increasing weakness and inability to swallow, which caused aspiration events without developing pneumonia.

The patient’s symptoms worsened while he was on steroids, and we became concerned about the possibility of a primary malignancy, which led to further work-up. The results of a computed-tomography (CT) scan of the abdomen and pelvis showed right-sided hydronephrosis and hydrourteter with an irregular, soft-tissue density mass of 4.7 x 3.2 x 4.2 cm along the posterior wall of the bladder (Figure 1).

Discussion

Dermatomyositis is one of the inflammatory myopathies with a clinical presentation of proximal muscle weakness and characteristic skin findings of Gottron papules and heliotrope eruption. The most common subgroups of inflammatory myopathies are dermatomyositis, polymyositis, necrotizing autoimmune myopathy, and inclusion body myopathy. The pathogenesis of inflammatory myopathies is not well understood; however, some theories have been described, including: type 1 interferon signaling causing myofiber injury and antibody-complement mediated processes causing ischemia resulting in myofiber injury. ^2,3 The diagnoses of inflammatory myopathies may be suggested based on history, physical examination findings, laboratory values showing muscle injury (creatine kinase, aldolase, ALT, AST, LDH), myositis-specific antibodies (antisynthetase autoantibodies), electromyogram, and magnetic-resonance imaging. However, muscle biopsy remains the gold standard.⁴

The initial treatment of inflammatory myopathies begins with glucocorticoid therapy at 0.5-1.0 mg/kg. This regimen may be titrated down over 6 weeks to a level adequate to control symptoms. Even while on glucocorticoid therapy, this patient’s symptoms continued, along with the development of dysphagia. Dysphagia is another notable symptom of dermatomyositis that may result in aspiration pneumonia with fatal outcomes.^5,6,7 Not only did this patient initially respond poorly to corticosteroids, but the unintentional weight loss was another alarming feature prompting further evaluation. That led to the diagnosis of urothelial cell carcinoma, which was causing the paraneoplastic syndrome.

A paraneoplastic syndrome is a collection of symptoms that are observed in organ systems separate from the primary disease. This process is mostly caused by an autoimmune response to the tumor and nervous system.⁸ Inflammatory myopathies, such as dermatomyositis, have been shown to be associated with a variety of malignancies as part of a paraneoplastic syndrome. The most common cancers associated with dermatomyositis are ovarian, lung, pancreatic, stomach, colorectal, and non-Hodgkin lymphoma.⁹ Although an association between dermatomyositis and bladder cancer has been established, very few cases have been reported in the literature. In the Yang meta-analysis, the relative risk of malignancy for patients with dermatomyositis was 5.5%, and of the 449 patients with dermatomyositis who had malignancy, only 8 cases of bladder cancer were reported.¹

After a patient has been diagnosed with an inflammatory myopathy, there should be further evaluation for an underling malignancy causing a paraneoplastic process. The risk of these patients having a malignancy overall is 4.5 times higher than patients without dermatomyositis.¹ Definite screening recommendations have not been established, but screening should be based on patient’s age, gender, and clinical scenario. The European Federation of Neurological Societies formed a task force to focus on malignancy screening of paraneoplastic neurological syndromes and included dermatomyositis as one of the signs.¹⁰ Patients should have a CT scan of the chest, abdomen, and pelvis. Women should have a mammogram and a pelvis ultrasound. Men younger than 50 years should consider testes ultrasound, and patients older than 50 years should undergo usual colonoscopy screening.

The risk of malignancy is highest in the first year after diagnosis, but may extend to 5 years after the diagnosis, so repeat screening should be performed 3-6 months after diagnosis, followed with biannual testing for 4 years. If a malignancy is present, then treatment should be tailored to the neoplasm to improve symptoms of myositis; however, response is generally worse than it would be with dermatomyositis in the absence of malignancy. In the present case with bladder cancer, therapies may include platinum-based-chemotherapy, resection, and radiation. Dermatomyositis as a result of a bladder cancer paraneoplastic syndrome is associated with a poor prognosis as demonstrated in the case of this patient and others reported in the literature.¹¹

Even though dermatomyositis is usually a chronic disease process, 87% of patients respond initially to corticosteroid treatment.¹² Therefore, treatment should be escalated with an agent such as azathioprine or methotrexate, or, like in this case, an underlying malignancy should be suspected. This case emphasizes the importance of screening patients appropriately for malignancy in patients with an inflammatory myopathy and reveals the poor prognosis associated with this disease.

The clinical presentation of bladder cancer typically presents with hematuria; changes in voiding habits such as urgency, frequency, and pain; or less commonly, obstructive symptoms. Rarely does bladder cancer first present as part of a paraneoplastic syndrome with an inflammatory myopathy. Inflammatory myopathies such as dermatomyositis have been known to be associated with malignancy, however, in a meta-analysis by Yang and colleagues of 449 patients with dermatomyositis and malignancy there were only 8 cases reported of bladder cancer.¹ Herein, we report a paraneoplastic dermatomyositis in the setting of a bladder cancer.

Case presentation and summary

A 65-year-old man with a medical history of hypertension and alcohol use presented to the emergency department with worsening pain, stiffness in the neck, shoulders, and inability to lift his arms above his shoulders. During the physical exam, an erythematous purple rash was noted over his chest, neck, and arms. Upon further evaluation, his creatine phosphokinase was 3,500 U/L (reference range 52-336 U/L) suggesting muscle breakdown and possible inflammatory myopathy. A biopsy of the left deltoid and quadriceps muscles was performed and yielded a diagnosis of dermatomyositis. He was treated with prednisone 60 mg daily for his inflammatory myopathy. The patient also reported an unintentional weight loss of 20 lbs. and increasing weakness and inability to swallow, which caused aspiration events without developing pneumonia.

The patient’s symptoms worsened while he was on steroids, and we became concerned about the possibility of a primary malignancy, which led to further work-up. The results of a computed-tomography (CT) scan of the abdomen and pelvis showed right-sided hydronephrosis and hydrourteter with an irregular, soft-tissue density mass of 4.7 x 3.2 x 4.2 cm along the posterior wall of the bladder (Figure 1).

Discussion

Dermatomyositis is one of the inflammatory myopathies with a clinical presentation of proximal muscle weakness and characteristic skin findings of Gottron papules and heliotrope eruption. The most common subgroups of inflammatory myopathies are dermatomyositis, polymyositis, necrotizing autoimmune myopathy, and inclusion body myopathy. The pathogenesis of inflammatory myopathies is not well understood; however, some theories have been described, including: type 1 interferon signaling causing myofiber injury and antibody-complement mediated processes causing ischemia resulting in myofiber injury. ^2,3 The diagnoses of inflammatory myopathies may be suggested based on history, physical examination findings, laboratory values showing muscle injury (creatine kinase, aldolase, ALT, AST, LDH), myositis-specific antibodies (antisynthetase autoantibodies), electromyogram, and magnetic-resonance imaging. However, muscle biopsy remains the gold standard.⁴

The initial treatment of inflammatory myopathies begins with glucocorticoid therapy at 0.5-1.0 mg/kg. This regimen may be titrated down over 6 weeks to a level adequate to control symptoms. Even while on glucocorticoid therapy, this patient’s symptoms continued, along with the development of dysphagia. Dysphagia is another notable symptom of dermatomyositis that may result in aspiration pneumonia with fatal outcomes.^5,6,7 Not only did this patient initially respond poorly to corticosteroids, but the unintentional weight loss was another alarming feature prompting further evaluation. That led to the diagnosis of urothelial cell carcinoma, which was causing the paraneoplastic syndrome.

A paraneoplastic syndrome is a collection of symptoms that are observed in organ systems separate from the primary disease. This process is mostly caused by an autoimmune response to the tumor and nervous system.⁸ Inflammatory myopathies, such as dermatomyositis, have been shown to be associated with a variety of malignancies as part of a paraneoplastic syndrome. The most common cancers associated with dermatomyositis are ovarian, lung, pancreatic, stomach, colorectal, and non-Hodgkin lymphoma.⁹ Although an association between dermatomyositis and bladder cancer has been established, very few cases have been reported in the literature. In the Yang meta-analysis, the relative risk of malignancy for patients with dermatomyositis was 5.5%, and of the 449 patients with dermatomyositis who had malignancy, only 8 cases of bladder cancer were reported.¹

After a patient has been diagnosed with an inflammatory myopathy, there should be further evaluation for an underling malignancy causing a paraneoplastic process. The risk of these patients having a malignancy overall is 4.5 times higher than patients without dermatomyositis.¹ Definite screening recommendations have not been established, but screening should be based on patient’s age, gender, and clinical scenario. The European Federation of Neurological Societies formed a task force to focus on malignancy screening of paraneoplastic neurological syndromes and included dermatomyositis as one of the signs.¹⁰ Patients should have a CT scan of the chest, abdomen, and pelvis. Women should have a mammogram and a pelvis ultrasound. Men younger than 50 years should consider testes ultrasound, and patients older than 50 years should undergo usual colonoscopy screening.

The risk of malignancy is highest in the first year after diagnosis, but may extend to 5 years after the diagnosis, so repeat screening should be performed 3-6 months after diagnosis, followed with biannual testing for 4 years. If a malignancy is present, then treatment should be tailored to the neoplasm to improve symptoms of myositis; however, response is generally worse than it would be with dermatomyositis in the absence of malignancy. In the present case with bladder cancer, therapies may include platinum-based-chemotherapy, resection, and radiation. Dermatomyositis as a result of a bladder cancer paraneoplastic syndrome is associated with a poor prognosis as demonstrated in the case of this patient and others reported in the literature.¹¹

Even though dermatomyositis is usually a chronic disease process, 87% of patients respond initially to corticosteroid treatment.¹² Therefore, treatment should be escalated with an agent such as azathioprine or methotrexate, or, like in this case, an underlying malignancy should be suspected. This case emphasizes the importance of screening patients appropriately for malignancy in patients with an inflammatory myopathy and reveals the poor prognosis associated with this disease.

The clinical presentation of bladder cancer typically presents with hematuria; changes in voiding habits such as urgency, frequency, and pain; or less commonly, obstructive symptoms. Rarely does bladder cancer first present as part of a paraneoplastic syndrome with an inflammatory myopathy. Inflammatory myopathies such as dermatomyositis have been known to be associated with malignancy, however, in a meta-analysis by Yang and colleagues of 449 patients with dermatomyositis and malignancy there were only 8 cases reported of bladder cancer.¹ Herein, we report a paraneoplastic dermatomyositis in the setting of a bladder cancer.

Case presentation and summary

A 65-year-old man with a medical history of hypertension and alcohol use presented to the emergency department with worsening pain, stiffness in the neck, shoulders, and inability to lift his arms above his shoulders. During the physical exam, an erythematous purple rash was noted over his chest, neck, and arms. Upon further evaluation, his creatine phosphokinase was 3,500 U/L (reference range 52-336 U/L) suggesting muscle breakdown and possible inflammatory myopathy. A biopsy of the left deltoid and quadriceps muscles was performed and yielded a diagnosis of dermatomyositis. He was treated with prednisone 60 mg daily for his inflammatory myopathy. The patient also reported an unintentional weight loss of 20 lbs. and increasing weakness and inability to swallow, which caused aspiration events without developing pneumonia.

The patient’s symptoms worsened while he was on steroids, and we became concerned about the possibility of a primary malignancy, which led to further work-up. The results of a computed-tomography (CT) scan of the abdomen and pelvis showed right-sided hydronephrosis and hydrourteter with an irregular, soft-tissue density mass of 4.7 x 3.2 x 4.2 cm along the posterior wall of the bladder (Figure 1).

Discussion

Dermatomyositis is one of the inflammatory myopathies with a clinical presentation of proximal muscle weakness and characteristic skin findings of Gottron papules and heliotrope eruption. The most common subgroups of inflammatory myopathies are dermatomyositis, polymyositis, necrotizing autoimmune myopathy, and inclusion body myopathy. The pathogenesis of inflammatory myopathies is not well understood; however, some theories have been described, including: type 1 interferon signaling causing myofiber injury and antibody-complement mediated processes causing ischemia resulting in myofiber injury. ^2,3 The diagnoses of inflammatory myopathies may be suggested based on history, physical examination findings, laboratory values showing muscle injury (creatine kinase, aldolase, ALT, AST, LDH), myositis-specific antibodies (antisynthetase autoantibodies), electromyogram, and magnetic-resonance imaging. However, muscle biopsy remains the gold standard.⁴

The initial treatment of inflammatory myopathies begins with glucocorticoid therapy at 0.5-1.0 mg/kg. This regimen may be titrated down over 6 weeks to a level adequate to control symptoms. Even while on glucocorticoid therapy, this patient’s symptoms continued, along with the development of dysphagia. Dysphagia is another notable symptom of dermatomyositis that may result in aspiration pneumonia with fatal outcomes.^5,6,7 Not only did this patient initially respond poorly to corticosteroids, but the unintentional weight loss was another alarming feature prompting further evaluation. That led to the diagnosis of urothelial cell carcinoma, which was causing the paraneoplastic syndrome.

A paraneoplastic syndrome is a collection of symptoms that are observed in organ systems separate from the primary disease. This process is mostly caused by an autoimmune response to the tumor and nervous system.⁸ Inflammatory myopathies, such as dermatomyositis, have been shown to be associated with a variety of malignancies as part of a paraneoplastic syndrome. The most common cancers associated with dermatomyositis are ovarian, lung, pancreatic, stomach, colorectal, and non-Hodgkin lymphoma.⁹ Although an association between dermatomyositis and bladder cancer has been established, very few cases have been reported in the literature. In the Yang meta-analysis, the relative risk of malignancy for patients with dermatomyositis was 5.5%, and of the 449 patients with dermatomyositis who had malignancy, only 8 cases of bladder cancer were reported.¹

After a patient has been diagnosed with an inflammatory myopathy, there should be further evaluation for an underling malignancy causing a paraneoplastic process. The risk of these patients having a malignancy overall is 4.5 times higher than patients without dermatomyositis.¹ Definite screening recommendations have not been established, but screening should be based on patient’s age, gender, and clinical scenario. The European Federation of Neurological Societies formed a task force to focus on malignancy screening of paraneoplastic neurological syndromes and included dermatomyositis as one of the signs.¹⁰ Patients should have a CT scan of the chest, abdomen, and pelvis. Women should have a mammogram and a pelvis ultrasound. Men younger than 50 years should consider testes ultrasound, and patients older than 50 years should undergo usual colonoscopy screening.

The risk of malignancy is highest in the first year after diagnosis, but may extend to 5 years after the diagnosis, so repeat screening should be performed 3-6 months after diagnosis, followed with biannual testing for 4 years. If a malignancy is present, then treatment should be tailored to the neoplasm to improve symptoms of myositis; however, response is generally worse than it would be with dermatomyositis in the absence of malignancy. In the present case with bladder cancer, therapies may include platinum-based-chemotherapy, resection, and radiation. Dermatomyositis as a result of a bladder cancer paraneoplastic syndrome is associated with a poor prognosis as demonstrated in the case of this patient and others reported in the literature.¹¹

Even though dermatomyositis is usually a chronic disease process, 87% of patients respond initially to corticosteroid treatment.¹² Therefore, treatment should be escalated with an agent such as azathioprine or methotrexate, or, like in this case, an underlying malignancy should be suspected. This case emphasizes the importance of screening patients appropriately for malignancy in patients with an inflammatory myopathy and reveals the poor prognosis associated with this disease.

NEW ORLEANS– Preventing acute kidney injury and its progression in hospitalized patients deserves to be a high priority – and now there is finally proof that it’s doable, Harold M. Szerlip, MD, declared at the annual meeting of the American College of Physicians.

The PrevAKI study, a recent randomized controlled clinical trial conducted by German investigators, has demonstrated that the use of renal biomarkers to identify patients at high risk for acute kidney injury (AKI) after major cardiac surgery and providing them with a range of internationally recommended supportive measures known as the KDIGO (Kidney Disease: Improving Global Outcomes) care bundle reduced the occurrence of moderate-to-severe AKI by 34% (Intensive Care Med. 2017 Nov;43[11]:1551-61).

Bruce Jancin/MDedge News

The PrevAKI findings validate the concept of AKI ‘golden hours’ during which time potentially reversible early kidney injury detectable via renal biomarkers is occurring prior to the abrupt decline in kidney function measured by change in serum creatinine. “The problem with using change in creatinine to define AKI is the delay in diagnosis, which makes AKI more difficult to treat,” he explained.

The renal biomarkers utilized in PrevAKI were insulin-like growth factor binding protein-7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), as incorporated in the commercially available urinary NephroCheck test, which was administered to study participants 4 hours after cardiopulmonary bypass. A test result of 0.3 or more identified a group at high risk for AKI for randomization to the KDIGO bundle or usual care. The KDIGO bundle consists of discontinuation of nephrotoxic agents when feasible, early optimization of fluid status, and maintenance of perfusion pressure.

Patients known to be at increased risk for in-hospital AKI include the elderly, those with diabetes, patients with heart failure or other conditions prone to volume contraction or overload, those undergoing major surgery, individuals with chronic kidney disease, and patients with sepsis.

Dr. Szerlip singled out as particularly nephrotoxic several drugs widely used in hospitalized patients, including the combination of vancomycin plus piperacillin-tazobactam, which in a recent metaanalysis was found to have a number needed to harm of 11 in terms of AKI in comparison to vancomycin monotherapy or vancomycin in combination with cefepime or carbapenem (Crit Care Med. 2018 Jan;46[1]:12-20). He was also critical of the American Society of Anesthesiologists practice parameter recommending that in-hospital pain management plans for surgical patients include continuous regimens of NSAIDs or COX-2 inhibitors as a means of combating the ongoing opioid epidemic.

“These are highly toxic drugs to the kidney and we shouldn’t be using them,” Dr. Szerlip said.

He reported receiving research grants from LaJolla, Bayer, Akebia, and BioPorto, serving on a speakers’ bureau for Astute Medical, and acting as a consultant to Zs Pharma, Amarin, and LaJolla.

[email protected]

NEW ORLEANS– Preventing acute kidney injury and its progression in hospitalized patients deserves to be a high priority – and now there is finally proof that it’s doable, Harold M. Szerlip, MD, declared at the annual meeting of the American College of Physicians.

The PrevAKI study, a recent randomized controlled clinical trial conducted by German investigators, has demonstrated that the use of renal biomarkers to identify patients at high risk for acute kidney injury (AKI) after major cardiac surgery and providing them with a range of internationally recommended supportive measures known as the KDIGO (Kidney Disease: Improving Global Outcomes) care bundle reduced the occurrence of moderate-to-severe AKI by 34% (Intensive Care Med. 2017 Nov;43[11]:1551-61).

Bruce Jancin/MDedge News

The PrevAKI findings validate the concept of AKI ‘golden hours’ during which time potentially reversible early kidney injury detectable via renal biomarkers is occurring prior to the abrupt decline in kidney function measured by change in serum creatinine. “The problem with using change in creatinine to define AKI is the delay in diagnosis, which makes AKI more difficult to treat,” he explained.

The renal biomarkers utilized in PrevAKI were insulin-like growth factor binding protein-7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), as incorporated in the commercially available urinary NephroCheck test, which was administered to study participants 4 hours after cardiopulmonary bypass. A test result of 0.3 or more identified a group at high risk for AKI for randomization to the KDIGO bundle or usual care. The KDIGO bundle consists of discontinuation of nephrotoxic agents when feasible, early optimization of fluid status, and maintenance of perfusion pressure.

Patients known to be at increased risk for in-hospital AKI include the elderly, those with diabetes, patients with heart failure or other conditions prone to volume contraction or overload, those undergoing major surgery, individuals with chronic kidney disease, and patients with sepsis.

Dr. Szerlip singled out as particularly nephrotoxic several drugs widely used in hospitalized patients, including the combination of vancomycin plus piperacillin-tazobactam, which in a recent metaanalysis was found to have a number needed to harm of 11 in terms of AKI in comparison to vancomycin monotherapy or vancomycin in combination with cefepime or carbapenem (Crit Care Med. 2018 Jan;46[1]:12-20). He was also critical of the American Society of Anesthesiologists practice parameter recommending that in-hospital pain management plans for surgical patients include continuous regimens of NSAIDs or COX-2 inhibitors as a means of combating the ongoing opioid epidemic.

“These are highly toxic drugs to the kidney and we shouldn’t be using them,” Dr. Szerlip said.

He reported receiving research grants from LaJolla, Bayer, Akebia, and BioPorto, serving on a speakers’ bureau for Astute Medical, and acting as a consultant to Zs Pharma, Amarin, and LaJolla.

[email protected]

NEW ORLEANS– Preventing acute kidney injury and its progression in hospitalized patients deserves to be a high priority – and now there is finally proof that it’s doable, Harold M. Szerlip, MD, declared at the annual meeting of the American College of Physicians.

The PrevAKI study, a recent randomized controlled clinical trial conducted by German investigators, has demonstrated that the use of renal biomarkers to identify patients at high risk for acute kidney injury (AKI) after major cardiac surgery and providing them with a range of internationally recommended supportive measures known as the KDIGO (Kidney Disease: Improving Global Outcomes) care bundle reduced the occurrence of moderate-to-severe AKI by 34% (Intensive Care Med. 2017 Nov;43[11]:1551-61).

Bruce Jancin/MDedge News

The PrevAKI findings validate the concept of AKI ‘golden hours’ during which time potentially reversible early kidney injury detectable via renal biomarkers is occurring prior to the abrupt decline in kidney function measured by change in serum creatinine. “The problem with using change in creatinine to define AKI is the delay in diagnosis, which makes AKI more difficult to treat,” he explained.

The renal biomarkers utilized in PrevAKI were insulin-like growth factor binding protein-7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), as incorporated in the commercially available urinary NephroCheck test, which was administered to study participants 4 hours after cardiopulmonary bypass. A test result of 0.3 or more identified a group at high risk for AKI for randomization to the KDIGO bundle or usual care. The KDIGO bundle consists of discontinuation of nephrotoxic agents when feasible, early optimization of fluid status, and maintenance of perfusion pressure.

Patients known to be at increased risk for in-hospital AKI include the elderly, those with diabetes, patients with heart failure or other conditions prone to volume contraction or overload, those undergoing major surgery, individuals with chronic kidney disease, and patients with sepsis.

Dr. Szerlip singled out as particularly nephrotoxic several drugs widely used in hospitalized patients, including the combination of vancomycin plus piperacillin-tazobactam, which in a recent metaanalysis was found to have a number needed to harm of 11 in terms of AKI in comparison to vancomycin monotherapy or vancomycin in combination with cefepime or carbapenem (Crit Care Med. 2018 Jan;46[1]:12-20). He was also critical of the American Society of Anesthesiologists practice parameter recommending that in-hospital pain management plans for surgical patients include continuous regimens of NSAIDs or COX-2 inhibitors as a means of combating the ongoing opioid epidemic.

“These are highly toxic drugs to the kidney and we shouldn’t be using them,” Dr. Szerlip said.

He reported receiving research grants from LaJolla, Bayer, Akebia, and BioPorto, serving on a speakers’ bureau for Astute Medical, and acting as a consultant to Zs Pharma, Amarin, and LaJolla.

[email protected]

AUSTIN, TEXAS – A novel therapeutic agent shows promise for postpartum depression in a phase 3 trial presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

Brexanolone, administered intravenously, differs from other antidepressants currently used to treat postpartum depression. It targets GABA_A receptors, according to presenter Christine Clemson, PhD, senior medical director at Sage Therapeutics, the company developing brexanolone.

The randomized, placebo-controlled, double-blind study enrolled 138 women who were 6 months postpartum or less, and had been diagnosed with a major depressive episode during the third trimester or at 4 or fewer weeks postpartum, and had a 17-item Hamilton Rating Scale for Depression (HAM-D) score of 26 or greater.

They were randomized to either brexanolone 60 mcg/kg/hour or 90 mcg/kg/hour administered intravenously over 60 hours as inpatients, or placebo. All three groups were an average aged 27 years old, the majority were white, and they had a HAM-D score between 28.4 and 29.1 at baseline.

After the first 60 hours of treatment, patients in the brexanolone group had mean reductions in the HAM-D score of about 20 in the 60 mcg group (P less than .01) and 18 in the 90 mcg group (P less than .05), compared with almost 14 in the placebo group. This was the primary endpoint,

Patients retained improvement through day 30, while those in the placebo group experienced a slight swing in the opposite direction.

Adverse effects in the brexanolone-treated groups were minimal; the majority of events reported were headaches or dizziness. However, Dr. Clemson said that some patients had to stop breastfeeding for a week.

An application for brexanolone for treating postpartum depression was submitted to the Food and Drug Administration on April 23; if approved, it would be the first drug of its kind to become available to treat postpartum depression.

The study was funded by Sage Therapeutics; two of the six authors are company employees. Two authors, including the lead author, are from the department of psychiatry, at the University of North Carolina, Chapel Hill.

[email protected]

SOURCE: S. Meltzer-Brody S et al. ACOG 2018, Poster 29B.

AUSTIN, TEXAS – A novel therapeutic agent shows promise for postpartum depression in a phase 3 trial presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

Brexanolone, administered intravenously, differs from other antidepressants currently used to treat postpartum depression. It targets GABA_A receptors, according to presenter Christine Clemson, PhD, senior medical director at Sage Therapeutics, the company developing brexanolone.

The randomized, placebo-controlled, double-blind study enrolled 138 women who were 6 months postpartum or less, and had been diagnosed with a major depressive episode during the third trimester or at 4 or fewer weeks postpartum, and had a 17-item Hamilton Rating Scale for Depression (HAM-D) score of 26 or greater.

They were randomized to either brexanolone 60 mcg/kg/hour or 90 mcg/kg/hour administered intravenously over 60 hours as inpatients, or placebo. All three groups were an average aged 27 years old, the majority were white, and they had a HAM-D score between 28.4 and 29.1 at baseline.

After the first 60 hours of treatment, patients in the brexanolone group had mean reductions in the HAM-D score of about 20 in the 60 mcg group (P less than .01) and 18 in the 90 mcg group (P less than .05), compared with almost 14 in the placebo group. This was the primary endpoint,

Patients retained improvement through day 30, while those in the placebo group experienced a slight swing in the opposite direction.

Adverse effects in the brexanolone-treated groups were minimal; the majority of events reported were headaches or dizziness. However, Dr. Clemson said that some patients had to stop breastfeeding for a week.

An application for brexanolone for treating postpartum depression was submitted to the Food and Drug Administration on April 23; if approved, it would be the first drug of its kind to become available to treat postpartum depression.

The study was funded by Sage Therapeutics; two of the six authors are company employees. Two authors, including the lead author, are from the department of psychiatry, at the University of North Carolina, Chapel Hill.

[email protected]

SOURCE: S. Meltzer-Brody S et al. ACOG 2018, Poster 29B.

AUSTIN, TEXAS – A novel therapeutic agent shows promise for postpartum depression in a phase 3 trial presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

Brexanolone, administered intravenously, differs from other antidepressants currently used to treat postpartum depression. It targets GABA_A receptors, according to presenter Christine Clemson, PhD, senior medical director at Sage Therapeutics, the company developing brexanolone.

The randomized, placebo-controlled, double-blind study enrolled 138 women who were 6 months postpartum or less, and had been diagnosed with a major depressive episode during the third trimester or at 4 or fewer weeks postpartum, and had a 17-item Hamilton Rating Scale for Depression (HAM-D) score of 26 or greater.

They were randomized to either brexanolone 60 mcg/kg/hour or 90 mcg/kg/hour administered intravenously over 60 hours as inpatients, or placebo. All three groups were an average aged 27 years old, the majority were white, and they had a HAM-D score between 28.4 and 29.1 at baseline.

After the first 60 hours of treatment, patients in the brexanolone group had mean reductions in the HAM-D score of about 20 in the 60 mcg group (P less than .01) and 18 in the 90 mcg group (P less than .05), compared with almost 14 in the placebo group. This was the primary endpoint,

Patients retained improvement through day 30, while those in the placebo group experienced a slight swing in the opposite direction.

Adverse effects in the brexanolone-treated groups were minimal; the majority of events reported were headaches or dizziness. However, Dr. Clemson said that some patients had to stop breastfeeding for a week.

An application for brexanolone for treating postpartum depression was submitted to the Food and Drug Administration on April 23; if approved, it would be the first drug of its kind to become available to treat postpartum depression.

The study was funded by Sage Therapeutics; two of the six authors are company employees. Two authors, including the lead author, are from the department of psychiatry, at the University of North Carolina, Chapel Hill.

[email protected]

SOURCE: S. Meltzer-Brody S et al. ACOG 2018, Poster 29B.