Chronic viral infection can be associated with a variety of autoimmune kidney diseases, according to a review published in Rheumatic Disease Clinics.

London_England/Thinkstock

In particular, hepatitis C virus (HCV) infection can cause several kidney disorders. These include cryoglobulinemic glomerulonephritis, membranous nephropathy, fibrillary glomerulopathy, immunotactoid glomerulopathy, and IgA nephropathy, wrote Joshua D. Long and his colleagues at Massachusetts General Hospital, Boston.

Similarly, hepatitis B virus (HBV) infection was found to be associated with both membranous nephropathy and polyarteritis nodosa, and human immunodeficiency virus (HIV) infection can cause HIV-associated nephropathy and HIV-associated immune complex diseases, which affect the kidneys.

In their detailed review, the authors discussed the various causal mechanisms and clinical presentations of each of these various autoimmune kidney diseases caused by HCV, HBV, and HIV, along with current treatment modalities.

“Control of the kidney disease relies primarily on treatment of viremia with antiviral agents; however, immunosuppression also may be needed in severe cases,” said the reviewers. However, “more clinical trials are needed to determine first-line therapies for patients who develop autoimmune kidney diseases in the context of chronic viral infections and to define when adjunctive immunosuppressive therapy is warranted,” they concluded.

One of the authors reported grant support and acting as a consultant for various pharmaceutical companies.

[email protected]

SOURCE: Long JD et al. Rheum Dis Clin N Am 2018;44:675-98.

Chronic viral infection can be associated with a variety of autoimmune kidney diseases, according to a review published in Rheumatic Disease Clinics.

London_England/Thinkstock

In particular, hepatitis C virus (HCV) infection can cause several kidney disorders. These include cryoglobulinemic glomerulonephritis, membranous nephropathy, fibrillary glomerulopathy, immunotactoid glomerulopathy, and IgA nephropathy, wrote Joshua D. Long and his colleagues at Massachusetts General Hospital, Boston.

Similarly, hepatitis B virus (HBV) infection was found to be associated with both membranous nephropathy and polyarteritis nodosa, and human immunodeficiency virus (HIV) infection can cause HIV-associated nephropathy and HIV-associated immune complex diseases, which affect the kidneys.

In their detailed review, the authors discussed the various causal mechanisms and clinical presentations of each of these various autoimmune kidney diseases caused by HCV, HBV, and HIV, along with current treatment modalities.

“Control of the kidney disease relies primarily on treatment of viremia with antiviral agents; however, immunosuppression also may be needed in severe cases,” said the reviewers. However, “more clinical trials are needed to determine first-line therapies for patients who develop autoimmune kidney diseases in the context of chronic viral infections and to define when adjunctive immunosuppressive therapy is warranted,” they concluded.

One of the authors reported grant support and acting as a consultant for various pharmaceutical companies.

[email protected]

SOURCE: Long JD et al. Rheum Dis Clin N Am 2018;44:675-98.

Chronic viral infection can be associated with a variety of autoimmune kidney diseases, according to a review published in Rheumatic Disease Clinics.

London_England/Thinkstock

In particular, hepatitis C virus (HCV) infection can cause several kidney disorders. These include cryoglobulinemic glomerulonephritis, membranous nephropathy, fibrillary glomerulopathy, immunotactoid glomerulopathy, and IgA nephropathy, wrote Joshua D. Long and his colleagues at Massachusetts General Hospital, Boston.

Similarly, hepatitis B virus (HBV) infection was found to be associated with both membranous nephropathy and polyarteritis nodosa, and human immunodeficiency virus (HIV) infection can cause HIV-associated nephropathy and HIV-associated immune complex diseases, which affect the kidneys.

In their detailed review, the authors discussed the various causal mechanisms and clinical presentations of each of these various autoimmune kidney diseases caused by HCV, HBV, and HIV, along with current treatment modalities.

“Control of the kidney disease relies primarily on treatment of viremia with antiviral agents; however, immunosuppression also may be needed in severe cases,” said the reviewers. However, “more clinical trials are needed to determine first-line therapies for patients who develop autoimmune kidney diseases in the context of chronic viral infections and to define when adjunctive immunosuppressive therapy is warranted,” they concluded.

One of the authors reported grant support and acting as a consultant for various pharmaceutical companies.

[email protected]

SOURCE: Long JD et al. Rheum Dis Clin N Am 2018;44:675-98.

Editor’s note: Each month, the Society of Hospitalist Medicine puts the spotlight on some of our most active members who are making substantial contributions to hospital medicine. Visit www.hospitalmedicine.org for more information on how you can lend your expertise to help improve the care of hospitalized patients.

This month, The Hospitalist spotlights Barbara Egan, MD, FACP, SFHM, chief of the hospital medicine service in the department of medicine at Memorial Sloan Kettering Cancer Center in New York. Barbara has been a member of SHM since 2005, is dual certified in hospital medicine and palliative care, and is the chair of SHM’s Palliative Care Work Group.

When did you first hear about SHM, and why did you decide to become a member?

I first learned about SHM when I was an internal medicine resident at Brigham and Women’s Hospital, Boston, in the early 2000s. BWH had an extremely strong hospitalist group; the staff I worked with served as powerful role models for me and inspired my interest in becoming a hospitalist. One of my attendings suggested that I join SHM, which I did right after I graduated from residency. I attended my first SHM Annual Conference in 2005. By then, I was working as a hospitalist at Memorial Sloan Kettering Cancer Center. SHM and the field of hospital medicine have exploded since my career first began, and I am happy to have grown alongside them. Similarly, our hospital medicine group here at MSKCC has dramatically grown, from 1 hospitalist (me) to more than 30!

How did you get involved with SHM’s Palliative Care Work Group, and what has the work group accomplished since you joined?

I was honored to be invited to join SHM’s Palliative Care Work Group in 2017 by Wendy Anderson, MD, a colleague and now a friend from University of California, San Francisco. Wendy is a visionary leader who practices and researches at the intersection of palliative care and hospital medicine. She and I met during 2015, when we were both invited to join a collaboration between SHM and the Hastings Center in Garrison, N.Y., which was aimed at improving hospitalists’ ability to provide outstanding care to hospitalized patients with life-limiting illnesses. That collaboration resulted in the Improving Communication about Serious Illness–Implementation Guide, a compilation of resources and best practices.

Wendy was chairing the SHM Palliative Care Work Group and invited me to join, which I did with great enthusiasm. This group consists of several passionate and brilliant hospitalists whose practices, in a variety of ways, involve both hospital medicine and palliative medicine. I was so honored when Wendy passed the baton to me last spring and invited me to chair the Work Group. I am lucky to have the opportunity to collaborate with this group of dynamic individuals, and we are well supported by an outstanding SHM staff member, Nick Marzano.
 

Are there any new projects that the work group is currently focusing on?

The primary focus of SHM’s Palliative Care Work Group is educational. That is, we aim to assess and help meet the educational needs of hospitalists, thereby helping to empower them to be outstanding providers of primary palliative care to seriously ill, hospitalized patients. To that end, we were very proud to orchestrate a palliative care mini-track for the first time at HM18. To our group’s delight, the attendance and reviews of that track were great. Thus, we were invited to further expand the palliative care offerings at HM19. We are busy planning for HM19: a full-day pre-course in palliative medicine; several podium presentations which will touch on ethical challenges, symptom management, prognostication, and other important topics; and a workshop in communication skills.
 

What led to your dual certification and how do your two specialties overlap?

I am board certified in internal medicine with Focused Practice in Hospital Medicine by virtue of my clinical training and my primary clinical practice as a hospitalist. As a hospitalist in a cancer center, I spend most of my time caring for patients with late- and end-stage malignancy. As such, early in my career, I had to develop a broad base of palliative medical skills, such as pain and symptom management and communication skills. I find this work extremely rewarding, albeit emotionally taxing. I have learned to redefine what clinical “success” looks like – my patients often have unfixable medical problems, but I can always strive to improve their lives in some way, even if that means helping to provide them with a painless, dignified death as opposed to curing them.

When the American Board of Medical Specialties established a board certification in Hospice and Palliative Medicine, there briefly existed a pathway to be “grandfathered” in, i.e., to qualify for board certification through an examination and clinical experience, as opposed to a fellowship. I jumped at the chance to formalize my palliative care skills and experience, and I attained board certification in 2012. This allowed me to further diversify my clinical practice here at MSKCC.

Hospital medicine is still my first love, and I spend most of my time practicing as a hospitalist on our solid tumor services. But now I also spend several weeks each year attending as a consultant on our inpatient supportive care service. In that role, I am able to collaborate with a fantastic multidisciplinary team consisting of MDs, NPs, a chaplain, a pharmacist, a social worker, and integrative medicine practitioners. I also love the opportunity to teach and mentor our palliative medicine fellows.

To me, the opportunity to marry hospital medicine and palliative medicine in my career was a natural fit. Hospitalists, particularly those caring exclusively for cancer patients like I do, need to provide excellent palliative care to our patients every day. The opportunity to further my training and to obtain board certification was a golden one, and I love being able to wear both hats here at MSKCC.
 

Ms. Steele is a marketing communications specialist at the Society of Hospital Medicine.

Editor’s note: Each month, the Society of Hospitalist Medicine puts the spotlight on some of our most active members who are making substantial contributions to hospital medicine. Visit www.hospitalmedicine.org for more information on how you can lend your expertise to help improve the care of hospitalized patients.

This month, The Hospitalist spotlights Barbara Egan, MD, FACP, SFHM, chief of the hospital medicine service in the department of medicine at Memorial Sloan Kettering Cancer Center in New York. Barbara has been a member of SHM since 2005, is dual certified in hospital medicine and palliative care, and is the chair of SHM’s Palliative Care Work Group.

When did you first hear about SHM, and why did you decide to become a member?

I first learned about SHM when I was an internal medicine resident at Brigham and Women’s Hospital, Boston, in the early 2000s. BWH had an extremely strong hospitalist group; the staff I worked with served as powerful role models for me and inspired my interest in becoming a hospitalist. One of my attendings suggested that I join SHM, which I did right after I graduated from residency. I attended my first SHM Annual Conference in 2005. By then, I was working as a hospitalist at Memorial Sloan Kettering Cancer Center. SHM and the field of hospital medicine have exploded since my career first began, and I am happy to have grown alongside them. Similarly, our hospital medicine group here at MSKCC has dramatically grown, from 1 hospitalist (me) to more than 30!

How did you get involved with SHM’s Palliative Care Work Group, and what has the work group accomplished since you joined?

I was honored to be invited to join SHM’s Palliative Care Work Group in 2017 by Wendy Anderson, MD, a colleague and now a friend from University of California, San Francisco. Wendy is a visionary leader who practices and researches at the intersection of palliative care and hospital medicine. She and I met during 2015, when we were both invited to join a collaboration between SHM and the Hastings Center in Garrison, N.Y., which was aimed at improving hospitalists’ ability to provide outstanding care to hospitalized patients with life-limiting illnesses. That collaboration resulted in the Improving Communication about Serious Illness–Implementation Guide, a compilation of resources and best practices.

Wendy was chairing the SHM Palliative Care Work Group and invited me to join, which I did with great enthusiasm. This group consists of several passionate and brilliant hospitalists whose practices, in a variety of ways, involve both hospital medicine and palliative medicine. I was so honored when Wendy passed the baton to me last spring and invited me to chair the Work Group. I am lucky to have the opportunity to collaborate with this group of dynamic individuals, and we are well supported by an outstanding SHM staff member, Nick Marzano.
 

Are there any new projects that the work group is currently focusing on?

The primary focus of SHM’s Palliative Care Work Group is educational. That is, we aim to assess and help meet the educational needs of hospitalists, thereby helping to empower them to be outstanding providers of primary palliative care to seriously ill, hospitalized patients. To that end, we were very proud to orchestrate a palliative care mini-track for the first time at HM18. To our group’s delight, the attendance and reviews of that track were great. Thus, we were invited to further expand the palliative care offerings at HM19. We are busy planning for HM19: a full-day pre-course in palliative medicine; several podium presentations which will touch on ethical challenges, symptom management, prognostication, and other important topics; and a workshop in communication skills.
 

What led to your dual certification and how do your two specialties overlap?

I am board certified in internal medicine with Focused Practice in Hospital Medicine by virtue of my clinical training and my primary clinical practice as a hospitalist. As a hospitalist in a cancer center, I spend most of my time caring for patients with late- and end-stage malignancy. As such, early in my career, I had to develop a broad base of palliative medical skills, such as pain and symptom management and communication skills. I find this work extremely rewarding, albeit emotionally taxing. I have learned to redefine what clinical “success” looks like – my patients often have unfixable medical problems, but I can always strive to improve their lives in some way, even if that means helping to provide them with a painless, dignified death as opposed to curing them.

When the American Board of Medical Specialties established a board certification in Hospice and Palliative Medicine, there briefly existed a pathway to be “grandfathered” in, i.e., to qualify for board certification through an examination and clinical experience, as opposed to a fellowship. I jumped at the chance to formalize my palliative care skills and experience, and I attained board certification in 2012. This allowed me to further diversify my clinical practice here at MSKCC.

Hospital medicine is still my first love, and I spend most of my time practicing as a hospitalist on our solid tumor services. But now I also spend several weeks each year attending as a consultant on our inpatient supportive care service. In that role, I am able to collaborate with a fantastic multidisciplinary team consisting of MDs, NPs, a chaplain, a pharmacist, a social worker, and integrative medicine practitioners. I also love the opportunity to teach and mentor our palliative medicine fellows.

To me, the opportunity to marry hospital medicine and palliative medicine in my career was a natural fit. Hospitalists, particularly those caring exclusively for cancer patients like I do, need to provide excellent palliative care to our patients every day. The opportunity to further my training and to obtain board certification was a golden one, and I love being able to wear both hats here at MSKCC.
 

Ms. Steele is a marketing communications specialist at the Society of Hospital Medicine.

Editor’s note: Each month, the Society of Hospitalist Medicine puts the spotlight on some of our most active members who are making substantial contributions to hospital medicine. Visit www.hospitalmedicine.org for more information on how you can lend your expertise to help improve the care of hospitalized patients.

This month, The Hospitalist spotlights Barbara Egan, MD, FACP, SFHM, chief of the hospital medicine service in the department of medicine at Memorial Sloan Kettering Cancer Center in New York. Barbara has been a member of SHM since 2005, is dual certified in hospital medicine and palliative care, and is the chair of SHM’s Palliative Care Work Group.

When did you first hear about SHM, and why did you decide to become a member?

I first learned about SHM when I was an internal medicine resident at Brigham and Women’s Hospital, Boston, in the early 2000s. BWH had an extremely strong hospitalist group; the staff I worked with served as powerful role models for me and inspired my interest in becoming a hospitalist. One of my attendings suggested that I join SHM, which I did right after I graduated from residency. I attended my first SHM Annual Conference in 2005. By then, I was working as a hospitalist at Memorial Sloan Kettering Cancer Center. SHM and the field of hospital medicine have exploded since my career first began, and I am happy to have grown alongside them. Similarly, our hospital medicine group here at MSKCC has dramatically grown, from 1 hospitalist (me) to more than 30!

How did you get involved with SHM’s Palliative Care Work Group, and what has the work group accomplished since you joined?

I was honored to be invited to join SHM’s Palliative Care Work Group in 2017 by Wendy Anderson, MD, a colleague and now a friend from University of California, San Francisco. Wendy is a visionary leader who practices and researches at the intersection of palliative care and hospital medicine. She and I met during 2015, when we were both invited to join a collaboration between SHM and the Hastings Center in Garrison, N.Y., which was aimed at improving hospitalists’ ability to provide outstanding care to hospitalized patients with life-limiting illnesses. That collaboration resulted in the Improving Communication about Serious Illness–Implementation Guide, a compilation of resources and best practices.

Wendy was chairing the SHM Palliative Care Work Group and invited me to join, which I did with great enthusiasm. This group consists of several passionate and brilliant hospitalists whose practices, in a variety of ways, involve both hospital medicine and palliative medicine. I was so honored when Wendy passed the baton to me last spring and invited me to chair the Work Group. I am lucky to have the opportunity to collaborate with this group of dynamic individuals, and we are well supported by an outstanding SHM staff member, Nick Marzano.
 

Are there any new projects that the work group is currently focusing on?

The primary focus of SHM’s Palliative Care Work Group is educational. That is, we aim to assess and help meet the educational needs of hospitalists, thereby helping to empower them to be outstanding providers of primary palliative care to seriously ill, hospitalized patients. To that end, we were very proud to orchestrate a palliative care mini-track for the first time at HM18. To our group’s delight, the attendance and reviews of that track were great. Thus, we were invited to further expand the palliative care offerings at HM19. We are busy planning for HM19: a full-day pre-course in palliative medicine; several podium presentations which will touch on ethical challenges, symptom management, prognostication, and other important topics; and a workshop in communication skills.
 

What led to your dual certification and how do your two specialties overlap?

I am board certified in internal medicine with Focused Practice in Hospital Medicine by virtue of my clinical training and my primary clinical practice as a hospitalist. As a hospitalist in a cancer center, I spend most of my time caring for patients with late- and end-stage malignancy. As such, early in my career, I had to develop a broad base of palliative medical skills, such as pain and symptom management and communication skills. I find this work extremely rewarding, albeit emotionally taxing. I have learned to redefine what clinical “success” looks like – my patients often have unfixable medical problems, but I can always strive to improve their lives in some way, even if that means helping to provide them with a painless, dignified death as opposed to curing them.

When the American Board of Medical Specialties established a board certification in Hospice and Palliative Medicine, there briefly existed a pathway to be “grandfathered” in, i.e., to qualify for board certification through an examination and clinical experience, as opposed to a fellowship. I jumped at the chance to formalize my palliative care skills and experience, and I attained board certification in 2012. This allowed me to further diversify my clinical practice here at MSKCC.

Hospital medicine is still my first love, and I spend most of my time practicing as a hospitalist on our solid tumor services. But now I also spend several weeks each year attending as a consultant on our inpatient supportive care service. In that role, I am able to collaborate with a fantastic multidisciplinary team consisting of MDs, NPs, a chaplain, a pharmacist, a social worker, and integrative medicine practitioners. I also love the opportunity to teach and mentor our palliative medicine fellows.

To me, the opportunity to marry hospital medicine and palliative medicine in my career was a natural fit. Hospitalists, particularly those caring exclusively for cancer patients like I do, need to provide excellent palliative care to our patients every day. The opportunity to further my training and to obtain board certification was a golden one, and I love being able to wear both hats here at MSKCC.
 

Ms. Steele is a marketing communications specialist at the Society of Hospital Medicine.

Alveolar soft part sarcoma (ASPS) has often proven to be resistant to conventional doxorubicin-based chemotherapy, but tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) may provide new treatment strategies for this rare type of sarcoma, according to a literature review.

A rare, translocation-driven sarcoma of the soft tissues, ASPS often affects young adults and is characterized by indolent behavior and early metastasis. Despite its resistance to chemotherapy, studies indicate that survival is often prolonged in patients with metastatic disease. The literature has shown 5-year survival rates at about 60%, and this percentage has remained fairly consistent for the past 3 decades.

Luca Paoluzzi, MD, of New York University, and Robert G. Maki, MD, PhD, of Hofstra University, Hempstead, N.Y., reviewed the literature from 1952 to March 2018, in order to gain a better understanding of ASPS and the opportunities “for the translation of such knowledge into clinical practice,” they wrote in JAMA.

From a therapeutic standpoint, ASPS is characterized by sensitivity to vascular endothelial growth factor receptor–predominant TKIs, compared with other soft tissue sarcomas (STS), and recent data have emphasized that it is responsive to new immunotherapy regimens including ICIs. Pazopanib is currently the only agent that has received regulatory approval for use in STS refractory to other treatments and it appears to have consistent activity in metastatic ASPS. Management of ASPS generally also involves surgical resection and/or systemic treatment for metastatic disease. Conventional agents such as anthracycline-based chemotherapy have demonstrated a poor response rate lower than 10%, and while a complete resection may be curative, metastases are common and can occur years after resection of the primary tumor.

Conversely, ICIs “represent a promising area of drug development in ASPS; the data to date are limited but encouraging,” wrote Dr. Paoluzzi and Dr. Maki.

They pointed to one study that included 50 patients with sarcoma with 14 different subtypes of STS who were enrolled in immunotherapy trials conducted at the University of Texas MD Anderson Cancer Center, Houston. There were two pretreated patients with ASPS (two to four prior lines) in the cohort who received antiprogrammed death-ligand 1–based therapy, and achieved a partial response bordering on a complete response that lasted 8 and 12 months. An additional two patients achieved stable disease.

Another paper, presented at the 2017 Connective Tissue Oncology Society annual meeting, presented preliminary data from a phase 2 study that showed four of nine evaluable patients with ASPS treated with the TKI axitinib, combined with pembrolizumab, achieved a partial response. Three others had stable disease.

“Pathway-driven basket trials facilitate the enrollment of patients with such uncommon cancers and should provide valuable information regarding a second type of immune responsiveness to ICIs, one that is not a function of high tumor mutational burden,” the authors concluded.

No outside funding sources were reported. Dr. Maki reported receiving consultant fees from numerous sources and research support to New York University from Immune Design, Immunocore, Eli Lilly, Presage Biosciences, TRACON Pharmaceuticals, SARC, Regeneron, and Genentech. No other conflicts were reported.

SOURCE: Paoluzzi L et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4490.

Alveolar soft part sarcoma (ASPS) has often proven to be resistant to conventional doxorubicin-based chemotherapy, but tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) may provide new treatment strategies for this rare type of sarcoma, according to a literature review.

A rare, translocation-driven sarcoma of the soft tissues, ASPS often affects young adults and is characterized by indolent behavior and early metastasis. Despite its resistance to chemotherapy, studies indicate that survival is often prolonged in patients with metastatic disease. The literature has shown 5-year survival rates at about 60%, and this percentage has remained fairly consistent for the past 3 decades.

Luca Paoluzzi, MD, of New York University, and Robert G. Maki, MD, PhD, of Hofstra University, Hempstead, N.Y., reviewed the literature from 1952 to March 2018, in order to gain a better understanding of ASPS and the opportunities “for the translation of such knowledge into clinical practice,” they wrote in JAMA.

From a therapeutic standpoint, ASPS is characterized by sensitivity to vascular endothelial growth factor receptor–predominant TKIs, compared with other soft tissue sarcomas (STS), and recent data have emphasized that it is responsive to new immunotherapy regimens including ICIs. Pazopanib is currently the only agent that has received regulatory approval for use in STS refractory to other treatments and it appears to have consistent activity in metastatic ASPS. Management of ASPS generally also involves surgical resection and/or systemic treatment for metastatic disease. Conventional agents such as anthracycline-based chemotherapy have demonstrated a poor response rate lower than 10%, and while a complete resection may be curative, metastases are common and can occur years after resection of the primary tumor.

Conversely, ICIs “represent a promising area of drug development in ASPS; the data to date are limited but encouraging,” wrote Dr. Paoluzzi and Dr. Maki.

They pointed to one study that included 50 patients with sarcoma with 14 different subtypes of STS who were enrolled in immunotherapy trials conducted at the University of Texas MD Anderson Cancer Center, Houston. There were two pretreated patients with ASPS (two to four prior lines) in the cohort who received antiprogrammed death-ligand 1–based therapy, and achieved a partial response bordering on a complete response that lasted 8 and 12 months. An additional two patients achieved stable disease.

Another paper, presented at the 2017 Connective Tissue Oncology Society annual meeting, presented preliminary data from a phase 2 study that showed four of nine evaluable patients with ASPS treated with the TKI axitinib, combined with pembrolizumab, achieved a partial response. Three others had stable disease.

“Pathway-driven basket trials facilitate the enrollment of patients with such uncommon cancers and should provide valuable information regarding a second type of immune responsiveness to ICIs, one that is not a function of high tumor mutational burden,” the authors concluded.

No outside funding sources were reported. Dr. Maki reported receiving consultant fees from numerous sources and research support to New York University from Immune Design, Immunocore, Eli Lilly, Presage Biosciences, TRACON Pharmaceuticals, SARC, Regeneron, and Genentech. No other conflicts were reported.

SOURCE: Paoluzzi L et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4490.

Alveolar soft part sarcoma (ASPS) has often proven to be resistant to conventional doxorubicin-based chemotherapy, but tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) may provide new treatment strategies for this rare type of sarcoma, according to a literature review.

A rare, translocation-driven sarcoma of the soft tissues, ASPS often affects young adults and is characterized by indolent behavior and early metastasis. Despite its resistance to chemotherapy, studies indicate that survival is often prolonged in patients with metastatic disease. The literature has shown 5-year survival rates at about 60%, and this percentage has remained fairly consistent for the past 3 decades.

Luca Paoluzzi, MD, of New York University, and Robert G. Maki, MD, PhD, of Hofstra University, Hempstead, N.Y., reviewed the literature from 1952 to March 2018, in order to gain a better understanding of ASPS and the opportunities “for the translation of such knowledge into clinical practice,” they wrote in JAMA.

From a therapeutic standpoint, ASPS is characterized by sensitivity to vascular endothelial growth factor receptor–predominant TKIs, compared with other soft tissue sarcomas (STS), and recent data have emphasized that it is responsive to new immunotherapy regimens including ICIs. Pazopanib is currently the only agent that has received regulatory approval for use in STS refractory to other treatments and it appears to have consistent activity in metastatic ASPS. Management of ASPS generally also involves surgical resection and/or systemic treatment for metastatic disease. Conventional agents such as anthracycline-based chemotherapy have demonstrated a poor response rate lower than 10%, and while a complete resection may be curative, metastases are common and can occur years after resection of the primary tumor.

Conversely, ICIs “represent a promising area of drug development in ASPS; the data to date are limited but encouraging,” wrote Dr. Paoluzzi and Dr. Maki.

They pointed to one study that included 50 patients with sarcoma with 14 different subtypes of STS who were enrolled in immunotherapy trials conducted at the University of Texas MD Anderson Cancer Center, Houston. There were two pretreated patients with ASPS (two to four prior lines) in the cohort who received antiprogrammed death-ligand 1–based therapy, and achieved a partial response bordering on a complete response that lasted 8 and 12 months. An additional two patients achieved stable disease.

Another paper, presented at the 2017 Connective Tissue Oncology Society annual meeting, presented preliminary data from a phase 2 study that showed four of nine evaluable patients with ASPS treated with the TKI axitinib, combined with pembrolizumab, achieved a partial response. Three others had stable disease.

“Pathway-driven basket trials facilitate the enrollment of patients with such uncommon cancers and should provide valuable information regarding a second type of immune responsiveness to ICIs, one that is not a function of high tumor mutational burden,” the authors concluded.

No outside funding sources were reported. Dr. Maki reported receiving consultant fees from numerous sources and research support to New York University from Immune Design, Immunocore, Eli Lilly, Presage Biosciences, TRACON Pharmaceuticals, SARC, Regeneron, and Genentech. No other conflicts were reported.

SOURCE: Paoluzzi L et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4490.

Both age and type of insurance are significantly associated with greater delays in treatment of febrile urinary tract infections (UTIs), even after adjustment for confounders, according to a report in the Journal of Pediatrics.

Zizulhalmi/Thinkstock

Stephanie W. Hum and Nader Shaikh, MD, MPH, of the University of Pittsburgh, drew from data provided by two studies, Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation. Specifically, they extracted data regarding patients’ age, sex, history of UTIs, ethnicity, race, insurance, household size, and duration of fever before initiation of antimicrobial therapy, as well as primary caregivers’ level of education and income. Some factors were analyzed because of associations seen in adult studies, and others because of concerns about access to care. In this analysis, the researchers defined “treatment delay” as the number of hours between onset of fever and initiation of antimicrobial treatment and, after exclusion of afebrile children and those with missing data, included 660 patients.

In univariate analysis, both older age and commercial insurance were found to be significantly associated with delays in treatment. Compared with time to treatment seen with younger children, treatment was delayed by an average of 26.2 hours in children aged 12 months and older (P less than .001). Patients with commercial insurance were treated a mean of 12.6 hours later than were those with noncommercial insurance (P = .002). These associations remained significant even after adjustment in a multivariable regression model for sex, history of UTIs, ethnicity, race, primary caregivers’ level of education, insurance, and income level.

The finding regarding age is consistent with a previous study, and Ms. Hum and Dr. Shaikh suggested it may reflect parents experiencing reduced urgency regarding febrile illnesses among older children. However, the researchers also noted that greater rates of renal scarring are seen in older children, so “it seems important to educate physicians, parents, and triage nurses about the importance of early evaluation of children with fever,” even those older than 12 months.

The finding regarding insurance status, however, is contrary to what studies in adult populations have found, as well as those in pediatric EDs. The researchers suggested that perhaps parents with noncommercial insurance are more likely to take their children to EDs, where testing can be done on-site 24 hours a day, rather than to private clinics, which often have to send out testing to off-site laboratories.

One of the strengths of the study is its relatively large sample size, they said. Among its weaknesses is that treatment delays were self-reported by parents and might be inaccurate and that information regarding location of initial evaluation was not gathered and could not be examined with other factors.

This study was supported by a T35 training grant from the National Institute of Diabetes and Digestive and Kidney Diseases, sponsored by Tom R. Kleyman, MD, chief of the renal-electrolyte division at the University of Pittsburgh. The authors declared no conflicts of interest.

[email protected]

SOURCE: Hum SW et al. J Pediatr. 2018 Oct 16. doi: 10.1016/j.jpeds.2018.09.029.

This article was updated 10/24/18.

Both age and type of insurance are significantly associated with greater delays in treatment of febrile urinary tract infections (UTIs), even after adjustment for confounders, according to a report in the Journal of Pediatrics.

Zizulhalmi/Thinkstock

Stephanie W. Hum and Nader Shaikh, MD, MPH, of the University of Pittsburgh, drew from data provided by two studies, Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation. Specifically, they extracted data regarding patients’ age, sex, history of UTIs, ethnicity, race, insurance, household size, and duration of fever before initiation of antimicrobial therapy, as well as primary caregivers’ level of education and income. Some factors were analyzed because of associations seen in adult studies, and others because of concerns about access to care. In this analysis, the researchers defined “treatment delay” as the number of hours between onset of fever and initiation of antimicrobial treatment and, after exclusion of afebrile children and those with missing data, included 660 patients.

In univariate analysis, both older age and commercial insurance were found to be significantly associated with delays in treatment. Compared with time to treatment seen with younger children, treatment was delayed by an average of 26.2 hours in children aged 12 months and older (P less than .001). Patients with commercial insurance were treated a mean of 12.6 hours later than were those with noncommercial insurance (P = .002). These associations remained significant even after adjustment in a multivariable regression model for sex, history of UTIs, ethnicity, race, primary caregivers’ level of education, insurance, and income level.

The finding regarding age is consistent with a previous study, and Ms. Hum and Dr. Shaikh suggested it may reflect parents experiencing reduced urgency regarding febrile illnesses among older children. However, the researchers also noted that greater rates of renal scarring are seen in older children, so “it seems important to educate physicians, parents, and triage nurses about the importance of early evaluation of children with fever,” even those older than 12 months.

The finding regarding insurance status, however, is contrary to what studies in adult populations have found, as well as those in pediatric EDs. The researchers suggested that perhaps parents with noncommercial insurance are more likely to take their children to EDs, where testing can be done on-site 24 hours a day, rather than to private clinics, which often have to send out testing to off-site laboratories.

One of the strengths of the study is its relatively large sample size, they said. Among its weaknesses is that treatment delays were self-reported by parents and might be inaccurate and that information regarding location of initial evaluation was not gathered and could not be examined with other factors.

This study was supported by a T35 training grant from the National Institute of Diabetes and Digestive and Kidney Diseases, sponsored by Tom R. Kleyman, MD, chief of the renal-electrolyte division at the University of Pittsburgh. The authors declared no conflicts of interest.

[email protected]

SOURCE: Hum SW et al. J Pediatr. 2018 Oct 16. doi: 10.1016/j.jpeds.2018.09.029.

This article was updated 10/24/18.

Both age and type of insurance are significantly associated with greater delays in treatment of febrile urinary tract infections (UTIs), even after adjustment for confounders, according to a report in the Journal of Pediatrics.

Zizulhalmi/Thinkstock

Stephanie W. Hum and Nader Shaikh, MD, MPH, of the University of Pittsburgh, drew from data provided by two studies, Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation. Specifically, they extracted data regarding patients’ age, sex, history of UTIs, ethnicity, race, insurance, household size, and duration of fever before initiation of antimicrobial therapy, as well as primary caregivers’ level of education and income. Some factors were analyzed because of associations seen in adult studies, and others because of concerns about access to care. In this analysis, the researchers defined “treatment delay” as the number of hours between onset of fever and initiation of antimicrobial treatment and, after exclusion of afebrile children and those with missing data, included 660 patients.

In univariate analysis, both older age and commercial insurance were found to be significantly associated with delays in treatment. Compared with time to treatment seen with younger children, treatment was delayed by an average of 26.2 hours in children aged 12 months and older (P less than .001). Patients with commercial insurance were treated a mean of 12.6 hours later than were those with noncommercial insurance (P = .002). These associations remained significant even after adjustment in a multivariable regression model for sex, history of UTIs, ethnicity, race, primary caregivers’ level of education, insurance, and income level.

The finding regarding age is consistent with a previous study, and Ms. Hum and Dr. Shaikh suggested it may reflect parents experiencing reduced urgency regarding febrile illnesses among older children. However, the researchers also noted that greater rates of renal scarring are seen in older children, so “it seems important to educate physicians, parents, and triage nurses about the importance of early evaluation of children with fever,” even those older than 12 months.

The finding regarding insurance status, however, is contrary to what studies in adult populations have found, as well as those in pediatric EDs. The researchers suggested that perhaps parents with noncommercial insurance are more likely to take their children to EDs, where testing can be done on-site 24 hours a day, rather than to private clinics, which often have to send out testing to off-site laboratories.

One of the strengths of the study is its relatively large sample size, they said. Among its weaknesses is that treatment delays were self-reported by parents and might be inaccurate and that information regarding location of initial evaluation was not gathered and could not be examined with other factors.

This study was supported by a T35 training grant from the National Institute of Diabetes and Digestive and Kidney Diseases, sponsored by Tom R. Kleyman, MD, chief of the renal-electrolyte division at the University of Pittsburgh. The authors declared no conflicts of interest.

[email protected]

SOURCE: Hum SW et al. J Pediatr. 2018 Oct 16. doi: 10.1016/j.jpeds.2018.09.029.

This article was updated 10/24/18.

All women of reproductive age should be screened for intimate partner violence, according to updated recommendations from the U.S. Preventive Services Task Force.

Intimate partner violence (IPV), defined to include sexual violence, physical violence, and stalking, occurs in approximately 36% of women and 33% of men in the United States, the Task Force members said.

Photodisc/Thinkstock

The screening of women of reproductive age is a B recommendation. However, evidence remains insufficient to recommend routine screening for IPV for men, and screening for abuse in elders and vulnerable adult populations received an I statement based on insufficient evidence to assess the balance of risks and benefits, wrote Susan J. Curry, PhD, of the University of Iowa, Iowa City, and her colleagues. Vulnerable adults were defined as those who are not able to protect themselves because of age, disability, or both. The recommendations were published in JAMA.

The Task Force reviewed the available evidence and determined that screening tools can help identify intimate partner violence in women of reproductive age, and that support services can reduce the risk of physical, sexual, and psychological abuse in these women.

In the evidence review accompanying the recommendations, Cynthia Feltner, MD, MPH, of the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 30 studies including 14,959 individuals.

They reviewed studies of IPV for adolescents through women in their 40s and identified several screening tools that accurately detected IPV in adult women within the past year: Humiliation, Afraid, Rape, Kick (HARK); Hurt, Insulted, Threaten, Scream (HITS); Extended–Hurt, Insult, Threaten, Scream (E-HITS); Partner Violence Screen (PVS); and Woman Abuse Screening Tool (WAST). The sensitivity of these tools ranged from 65% to 87%, and specificity ranged from 80% to 95%.

Data from three randomized, controlled trials including 3,759 women found no benefit to screening them for IPV over 3-18 months, but no randomized, controlled trials found any harms associated with screening.

In addition, the data showed no evidence that screening reduced IPV or improved quality of life over a 3-18-month period, the researchers noted.

In addition, the Task Force researchers found no reliable screening tools to identify IPV in men or to identify abuse of elders or vulnerable adults in the absence of recognized signs and symptoms of abuse.

The complete recommendations are available online in JAMA, and on the USPSTF website: http://www.uspreventiveservicestaskforce.org.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.

SOURCES: Curry SJ et al. JAMA. 2018;320(16):1678-87; Feltner C et al. JAMA. 2018;320(16):1688-701.

All women of reproductive age should be screened for intimate partner violence, according to updated recommendations from the U.S. Preventive Services Task Force.

Intimate partner violence (IPV), defined to include sexual violence, physical violence, and stalking, occurs in approximately 36% of women and 33% of men in the United States, the Task Force members said.

Photodisc/Thinkstock

The screening of women of reproductive age is a B recommendation. However, evidence remains insufficient to recommend routine screening for IPV for men, and screening for abuse in elders and vulnerable adult populations received an I statement based on insufficient evidence to assess the balance of risks and benefits, wrote Susan J. Curry, PhD, of the University of Iowa, Iowa City, and her colleagues. Vulnerable adults were defined as those who are not able to protect themselves because of age, disability, or both. The recommendations were published in JAMA.

The Task Force reviewed the available evidence and determined that screening tools can help identify intimate partner violence in women of reproductive age, and that support services can reduce the risk of physical, sexual, and psychological abuse in these women.

In the evidence review accompanying the recommendations, Cynthia Feltner, MD, MPH, of the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 30 studies including 14,959 individuals.

They reviewed studies of IPV for adolescents through women in their 40s and identified several screening tools that accurately detected IPV in adult women within the past year: Humiliation, Afraid, Rape, Kick (HARK); Hurt, Insulted, Threaten, Scream (HITS); Extended–Hurt, Insult, Threaten, Scream (E-HITS); Partner Violence Screen (PVS); and Woman Abuse Screening Tool (WAST). The sensitivity of these tools ranged from 65% to 87%, and specificity ranged from 80% to 95%.

Data from three randomized, controlled trials including 3,759 women found no benefit to screening them for IPV over 3-18 months, but no randomized, controlled trials found any harms associated with screening.

In addition, the data showed no evidence that screening reduced IPV or improved quality of life over a 3-18-month period, the researchers noted.

In addition, the Task Force researchers found no reliable screening tools to identify IPV in men or to identify abuse of elders or vulnerable adults in the absence of recognized signs and symptoms of abuse.

The complete recommendations are available online in JAMA, and on the USPSTF website: http://www.uspreventiveservicestaskforce.org.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.

SOURCES: Curry SJ et al. JAMA. 2018;320(16):1678-87; Feltner C et al. JAMA. 2018;320(16):1688-701.

All women of reproductive age should be screened for intimate partner violence, according to updated recommendations from the U.S. Preventive Services Task Force.

Intimate partner violence (IPV), defined to include sexual violence, physical violence, and stalking, occurs in approximately 36% of women and 33% of men in the United States, the Task Force members said.

Photodisc/Thinkstock

The screening of women of reproductive age is a B recommendation. However, evidence remains insufficient to recommend routine screening for IPV for men, and screening for abuse in elders and vulnerable adult populations received an I statement based on insufficient evidence to assess the balance of risks and benefits, wrote Susan J. Curry, PhD, of the University of Iowa, Iowa City, and her colleagues. Vulnerable adults were defined as those who are not able to protect themselves because of age, disability, or both. The recommendations were published in JAMA.

The Task Force reviewed the available evidence and determined that screening tools can help identify intimate partner violence in women of reproductive age, and that support services can reduce the risk of physical, sexual, and psychological abuse in these women.

In the evidence review accompanying the recommendations, Cynthia Feltner, MD, MPH, of the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 30 studies including 14,959 individuals.

They reviewed studies of IPV for adolescents through women in their 40s and identified several screening tools that accurately detected IPV in adult women within the past year: Humiliation, Afraid, Rape, Kick (HARK); Hurt, Insulted, Threaten, Scream (HITS); Extended–Hurt, Insult, Threaten, Scream (E-HITS); Partner Violence Screen (PVS); and Woman Abuse Screening Tool (WAST). The sensitivity of these tools ranged from 65% to 87%, and specificity ranged from 80% to 95%.

Data from three randomized, controlled trials including 3,759 women found no benefit to screening them for IPV over 3-18 months, but no randomized, controlled trials found any harms associated with screening.

In addition, the data showed no evidence that screening reduced IPV or improved quality of life over a 3-18-month period, the researchers noted.

In addition, the Task Force researchers found no reliable screening tools to identify IPV in men or to identify abuse of elders or vulnerable adults in the absence of recognized signs and symptoms of abuse.

The complete recommendations are available online in JAMA, and on the USPSTF website: http://www.uspreventiveservicestaskforce.org.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.

SOURCES: Curry SJ et al. JAMA. 2018;320(16):1678-87; Feltner C et al. JAMA. 2018;320(16):1688-701.

MUNICH – Patients with HIV who are treated with nivolumab, a programmed death-1 (PD-1) inhibitor, appear to have similar safety and efficacy outcomes compared with HIV-negative patients treated with the same agent, investigators found.

The retrospective study also showed that viral load and CD4 status were largely unchanged by immunotherapy, lead author Aurélien Gobert, MD, of Groupe Hospitalier Pitié Salpêtrière, Paris, reported at the European Society for Medical Oncology Congress.

HIV increases risks of certain cancer types, Dr. Gobert said in a press release. “These patients are at higher risk for a number of cancers: AIDS-defining forms, the diagnosis of which results in the categorization of a person as suffering from AIDS, but also various other types that they are two to three times more likely to develop than in the general population, such as anal, skin, head and neck, and lung cancer,” he said.

Despite the increased risks, few studies have evaluated cancer treatments for patients with HIV due to exclusions from most clinical trials. As HIV is an immune-based disease, concerns have arisen surrounding the safety and efficacy of using anti-neoplastic immunotherapies for HIV-positive patients. Considering that millions of people worldwide are HIV positive, research in this area can have real-world consequences.

Dr. Gobert and his colleagues analyzed data from CANCERVIH, a French national database of patients with cancer and HIV. Since May 2014, nivolumab has been administered to 20 patients. Nineteen had metastatic non–small-cell lung cancer and 1 had metastatic melanoma. At diagnosis, the median CD4 count was 338.5 per cubic millimeter. Seventeen patients had undetectable viral load, two had fewer than 40 copies per millimeter, and one patient’s viral load was unknown. Dr. Gobert described the population as “demographically homogenous,” with “most patients being males around 60 years old.”

Analysis showed that nivolumab had little impact on CD4 count or viral load. One patient had a decreased CD4 count and an increased viral load, but this occurred during an interruption to antiretroviral therapy, which clouds potential associations with nivolumab. No immune-related adverse events or deaths due to drug toxicity occurred. Efficacy was assessed in 17 patients: Four (24%) showed a partial response, 2 (12%) had stable disease, and 11 (64%) had disease progression.

“Based on these preliminary data, treatment with anti-PD-1 ... seems to be feasible in people with HIV,” Dr. Gobert reported. He added that “antiretroviral therapy should not be interrupted.”

In a comment for ESMO, John Haanen, PhD, of the Netherlands Cancer Institute, Amsterdam, said that the results “confirm those of other, smaller cohorts in showing that while on antiretroviral therapy, cancer patients living with HIV can safely receive anti-PD-1 treatment. The efficacy data also suggests that the overall response rate of HIV-positive patients seems to be similar to that of other cancer patients. These promising results need to be confirmed in larger studies – ideally, in a prospective clinical trial.”

Principal investigator Jean-Philippe Spano, MD, PhD, disclosed relationships with Gilead, Roche, BMS, and others.

SOURCE: Gobert et al. ESMO 2018, Abstract 1213P_PR.

MUNICH – Patients with HIV who are treated with nivolumab, a programmed death-1 (PD-1) inhibitor, appear to have similar safety and efficacy outcomes compared with HIV-negative patients treated with the same agent, investigators found.

The retrospective study also showed that viral load and CD4 status were largely unchanged by immunotherapy, lead author Aurélien Gobert, MD, of Groupe Hospitalier Pitié Salpêtrière, Paris, reported at the European Society for Medical Oncology Congress.

HIV increases risks of certain cancer types, Dr. Gobert said in a press release. “These patients are at higher risk for a number of cancers: AIDS-defining forms, the diagnosis of which results in the categorization of a person as suffering from AIDS, but also various other types that they are two to three times more likely to develop than in the general population, such as anal, skin, head and neck, and lung cancer,” he said.

Despite the increased risks, few studies have evaluated cancer treatments for patients with HIV due to exclusions from most clinical trials. As HIV is an immune-based disease, concerns have arisen surrounding the safety and efficacy of using anti-neoplastic immunotherapies for HIV-positive patients. Considering that millions of people worldwide are HIV positive, research in this area can have real-world consequences.

Dr. Gobert and his colleagues analyzed data from CANCERVIH, a French national database of patients with cancer and HIV. Since May 2014, nivolumab has been administered to 20 patients. Nineteen had metastatic non–small-cell lung cancer and 1 had metastatic melanoma. At diagnosis, the median CD4 count was 338.5 per cubic millimeter. Seventeen patients had undetectable viral load, two had fewer than 40 copies per millimeter, and one patient’s viral load was unknown. Dr. Gobert described the population as “demographically homogenous,” with “most patients being males around 60 years old.”

Analysis showed that nivolumab had little impact on CD4 count or viral load. One patient had a decreased CD4 count and an increased viral load, but this occurred during an interruption to antiretroviral therapy, which clouds potential associations with nivolumab. No immune-related adverse events or deaths due to drug toxicity occurred. Efficacy was assessed in 17 patients: Four (24%) showed a partial response, 2 (12%) had stable disease, and 11 (64%) had disease progression.

“Based on these preliminary data, treatment with anti-PD-1 ... seems to be feasible in people with HIV,” Dr. Gobert reported. He added that “antiretroviral therapy should not be interrupted.”

In a comment for ESMO, John Haanen, PhD, of the Netherlands Cancer Institute, Amsterdam, said that the results “confirm those of other, smaller cohorts in showing that while on antiretroviral therapy, cancer patients living with HIV can safely receive anti-PD-1 treatment. The efficacy data also suggests that the overall response rate of HIV-positive patients seems to be similar to that of other cancer patients. These promising results need to be confirmed in larger studies – ideally, in a prospective clinical trial.”

Principal investigator Jean-Philippe Spano, MD, PhD, disclosed relationships with Gilead, Roche, BMS, and others.

SOURCE: Gobert et al. ESMO 2018, Abstract 1213P_PR.

MUNICH – Patients with HIV who are treated with nivolumab, a programmed death-1 (PD-1) inhibitor, appear to have similar safety and efficacy outcomes compared with HIV-negative patients treated with the same agent, investigators found.

The retrospective study also showed that viral load and CD4 status were largely unchanged by immunotherapy, lead author Aurélien Gobert, MD, of Groupe Hospitalier Pitié Salpêtrière, Paris, reported at the European Society for Medical Oncology Congress.

HIV increases risks of certain cancer types, Dr. Gobert said in a press release. “These patients are at higher risk for a number of cancers: AIDS-defining forms, the diagnosis of which results in the categorization of a person as suffering from AIDS, but also various other types that they are two to three times more likely to develop than in the general population, such as anal, skin, head and neck, and lung cancer,” he said.

Despite the increased risks, few studies have evaluated cancer treatments for patients with HIV due to exclusions from most clinical trials. As HIV is an immune-based disease, concerns have arisen surrounding the safety and efficacy of using anti-neoplastic immunotherapies for HIV-positive patients. Considering that millions of people worldwide are HIV positive, research in this area can have real-world consequences.

Dr. Gobert and his colleagues analyzed data from CANCERVIH, a French national database of patients with cancer and HIV. Since May 2014, nivolumab has been administered to 20 patients. Nineteen had metastatic non–small-cell lung cancer and 1 had metastatic melanoma. At diagnosis, the median CD4 count was 338.5 per cubic millimeter. Seventeen patients had undetectable viral load, two had fewer than 40 copies per millimeter, and one patient’s viral load was unknown. Dr. Gobert described the population as “demographically homogenous,” with “most patients being males around 60 years old.”

Analysis showed that nivolumab had little impact on CD4 count or viral load. One patient had a decreased CD4 count and an increased viral load, but this occurred during an interruption to antiretroviral therapy, which clouds potential associations with nivolumab. No immune-related adverse events or deaths due to drug toxicity occurred. Efficacy was assessed in 17 patients: Four (24%) showed a partial response, 2 (12%) had stable disease, and 11 (64%) had disease progression.

“Based on these preliminary data, treatment with anti-PD-1 ... seems to be feasible in people with HIV,” Dr. Gobert reported. He added that “antiretroviral therapy should not be interrupted.”

In a comment for ESMO, John Haanen, PhD, of the Netherlands Cancer Institute, Amsterdam, said that the results “confirm those of other, smaller cohorts in showing that while on antiretroviral therapy, cancer patients living with HIV can safely receive anti-PD-1 treatment. The efficacy data also suggests that the overall response rate of HIV-positive patients seems to be similar to that of other cancer patients. These promising results need to be confirmed in larger studies – ideally, in a prospective clinical trial.”

Principal investigator Jean-Philippe Spano, MD, PhD, disclosed relationships with Gilead, Roche, BMS, and others.

SOURCE: Gobert et al. ESMO 2018, Abstract 1213P_PR.

CHICAGO – Follow-up out to as long as 11 years from treatment confirmed the long-term efficacy and safety of myeloablative autologous stem cell transplantation for patients with severe scleroderma.

This extended follow-up comprised 43 survivors from the 75 patients originally randomized in a controlled, 6-year trial. Follow-up showed that, among the patients who underwent myeloablation and autologous transplant with hematopoietic stem cells, there were no long-term deaths or cancers, there was an 88% survival rate, and 92% remained off disease-modifying treatment, Keith M. Sullivan, MD, said at the annual meeting of the American College of Rheumatology.

Long-term survival among patients randomized to the study’s control arm, who received treatment with cyclophosphamide, was 53%.

Patients with severe scleroderma with significant internal organ damage who “are improved and off of disease-modifying antirheumatic drugs after 10 or more years from treatment is something new in autoimmune disease,” said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.

Based on accumulated data from this randomized trial and other studies, the American Society for Blood and Marrow Transplantation issued a position statement in June 2018 that endorsed autologous hematopoietic stem cell transplantation as “standard of care” for systemic sclerosis (Biol Blood Marrow Transplant. 2018 June 25. doi: 10.1016/j.bbmt.2018.06.025), Dr. Sullivan noted in a video interview.

The SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial randomized 75 patients with severe scleroderma and substantial internal organ involvement to receive treatment with either cyclophosphamide or myeloablative radiation followed by immune reconstitution with an autologous hematopoietic stem cell transplant. The trial’s primary endpoint, the global rank composite score at 54 months, showed the superiority of transplantation over standard treatment (N Engl J Med. 2018 Jan 4;378[1]:35-47).

Dr. Sullivan and his associates ran their long-term follow-up study on 43 of these 75 patients (25 from the transplanted group and 18 controls), excluding 21 patients who died during the original study, 4 additional patients from the control arm who died following the end of the original SCOT protocol, and 7 patients either lost to follow-up or who refused to participate in follow-up. Among the 25 transplanted patients, none died during the extended follow-up, 2 experienced cardiac failure, and 23 remained off of any disease-modifying antirheumatic drugs. Among the 18 survivors in the control arm, 3 had cardiac failure, 3 had respiratory failure, and 7 were on treatment with disease-modifying drugs, Dr. Sullivan reported.

In addition, 23 of the 25 (92%) transplanted patients had normal performance status by the Eastern Cooperative Oncology Group criteria, compared with 11 of the 18 controls (61%). A total of 14 (56%) transplant patients were employed, compared with 6 of the 18 controls (33%).

Patients who were transplanted “have their life back, are doing well, and are off treatment,” Dr. Sullivan noted.

Myeloablation and transplant is appropriate for scleroderma patients with significant internal organ involvement, about half of all patients with this disease. The best gauge of severe organ involvement is a pulmonary function test, with a forced vital capacity of 70% or less of predicted as a flag for patients who should consider transplantation, Dr. Sullivan said. He recommended monitoring lung function every 3 months in scleroderma patients because it can deteriorate very suddenly and quickly.

SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.

[email protected]

SOURCE: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.

CHICAGO – Follow-up out to as long as 11 years from treatment confirmed the long-term efficacy and safety of myeloablative autologous stem cell transplantation for patients with severe scleroderma.

This extended follow-up comprised 43 survivors from the 75 patients originally randomized in a controlled, 6-year trial. Follow-up showed that, among the patients who underwent myeloablation and autologous transplant with hematopoietic stem cells, there were no long-term deaths or cancers, there was an 88% survival rate, and 92% remained off disease-modifying treatment, Keith M. Sullivan, MD, said at the annual meeting of the American College of Rheumatology.

Long-term survival among patients randomized to the study’s control arm, who received treatment with cyclophosphamide, was 53%.

Patients with severe scleroderma with significant internal organ damage who “are improved and off of disease-modifying antirheumatic drugs after 10 or more years from treatment is something new in autoimmune disease,” said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.

Based on accumulated data from this randomized trial and other studies, the American Society for Blood and Marrow Transplantation issued a position statement in June 2018 that endorsed autologous hematopoietic stem cell transplantation as “standard of care” for systemic sclerosis (Biol Blood Marrow Transplant. 2018 June 25. doi: 10.1016/j.bbmt.2018.06.025), Dr. Sullivan noted in a video interview.

The SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial randomized 75 patients with severe scleroderma and substantial internal organ involvement to receive treatment with either cyclophosphamide or myeloablative radiation followed by immune reconstitution with an autologous hematopoietic stem cell transplant. The trial’s primary endpoint, the global rank composite score at 54 months, showed the superiority of transplantation over standard treatment (N Engl J Med. 2018 Jan 4;378[1]:35-47).

Dr. Sullivan and his associates ran their long-term follow-up study on 43 of these 75 patients (25 from the transplanted group and 18 controls), excluding 21 patients who died during the original study, 4 additional patients from the control arm who died following the end of the original SCOT protocol, and 7 patients either lost to follow-up or who refused to participate in follow-up. Among the 25 transplanted patients, none died during the extended follow-up, 2 experienced cardiac failure, and 23 remained off of any disease-modifying antirheumatic drugs. Among the 18 survivors in the control arm, 3 had cardiac failure, 3 had respiratory failure, and 7 were on treatment with disease-modifying drugs, Dr. Sullivan reported.

In addition, 23 of the 25 (92%) transplanted patients had normal performance status by the Eastern Cooperative Oncology Group criteria, compared with 11 of the 18 controls (61%). A total of 14 (56%) transplant patients were employed, compared with 6 of the 18 controls (33%).

Patients who were transplanted “have their life back, are doing well, and are off treatment,” Dr. Sullivan noted.

Myeloablation and transplant is appropriate for scleroderma patients with significant internal organ involvement, about half of all patients with this disease. The best gauge of severe organ involvement is a pulmonary function test, with a forced vital capacity of 70% or less of predicted as a flag for patients who should consider transplantation, Dr. Sullivan said. He recommended monitoring lung function every 3 months in scleroderma patients because it can deteriorate very suddenly and quickly.

SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.

[email protected]

SOURCE: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.

CHICAGO – Follow-up out to as long as 11 years from treatment confirmed the long-term efficacy and safety of myeloablative autologous stem cell transplantation for patients with severe scleroderma.

This extended follow-up comprised 43 survivors from the 75 patients originally randomized in a controlled, 6-year trial. Follow-up showed that, among the patients who underwent myeloablation and autologous transplant with hematopoietic stem cells, there were no long-term deaths or cancers, there was an 88% survival rate, and 92% remained off disease-modifying treatment, Keith M. Sullivan, MD, said at the annual meeting of the American College of Rheumatology.

Long-term survival among patients randomized to the study’s control arm, who received treatment with cyclophosphamide, was 53%.

Patients with severe scleroderma with significant internal organ damage who “are improved and off of disease-modifying antirheumatic drugs after 10 or more years from treatment is something new in autoimmune disease,” said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.

Based on accumulated data from this randomized trial and other studies, the American Society for Blood and Marrow Transplantation issued a position statement in June 2018 that endorsed autologous hematopoietic stem cell transplantation as “standard of care” for systemic sclerosis (Biol Blood Marrow Transplant. 2018 June 25. doi: 10.1016/j.bbmt.2018.06.025), Dr. Sullivan noted in a video interview.

The SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial randomized 75 patients with severe scleroderma and substantial internal organ involvement to receive treatment with either cyclophosphamide or myeloablative radiation followed by immune reconstitution with an autologous hematopoietic stem cell transplant. The trial’s primary endpoint, the global rank composite score at 54 months, showed the superiority of transplantation over standard treatment (N Engl J Med. 2018 Jan 4;378[1]:35-47).

Dr. Sullivan and his associates ran their long-term follow-up study on 43 of these 75 patients (25 from the transplanted group and 18 controls), excluding 21 patients who died during the original study, 4 additional patients from the control arm who died following the end of the original SCOT protocol, and 7 patients either lost to follow-up or who refused to participate in follow-up. Among the 25 transplanted patients, none died during the extended follow-up, 2 experienced cardiac failure, and 23 remained off of any disease-modifying antirheumatic drugs. Among the 18 survivors in the control arm, 3 had cardiac failure, 3 had respiratory failure, and 7 were on treatment with disease-modifying drugs, Dr. Sullivan reported.

In addition, 23 of the 25 (92%) transplanted patients had normal performance status by the Eastern Cooperative Oncology Group criteria, compared with 11 of the 18 controls (61%). A total of 14 (56%) transplant patients were employed, compared with 6 of the 18 controls (33%).

Patients who were transplanted “have their life back, are doing well, and are off treatment,” Dr. Sullivan noted.

Myeloablation and transplant is appropriate for scleroderma patients with significant internal organ involvement, about half of all patients with this disease. The best gauge of severe organ involvement is a pulmonary function test, with a forced vital capacity of 70% or less of predicted as a flag for patients who should consider transplantation, Dr. Sullivan said. He recommended monitoring lung function every 3 months in scleroderma patients because it can deteriorate very suddenly and quickly.

SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.

[email protected]

SOURCE: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.

Quality in medicine is a peculiar thing. It is clearly apparent, and yet, can be very difficult to measure and quantify. Surgery, a performance art of sorts, can be even more challenging to qualify or rate. However, as a means to elevate the quality of care for all patients, hospital systems and care providers have aggressively made attempts to do so. This is a noble objective.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

In September 2018, the Committee of Gynecologic Practice of the American College of Obstetricians and Gynecologists released ACOG Committee Opinion Number 750, titled, “Perioperative Pathways: Enhanced Recovery After Surgery.”¹

The goals of this committee opinion were to advocate for gynecologic surgeons using the “ERAS” pathways in their perioperative care as part of an evidenced-based approach to quality improvement. ERAS pathways have been previously discussed in this column and feature bundled perioperative pathways that incorporate various concepts such as avoidance of prolonged preoperative fasting, early postoperative feeding, multimodal analgesia (with an avoidance of opiates), and inclusion of antibiotic and antiembolic prophylaxis, among other elements.

What was alarming upon closer review of this ACOG Committee Opinion was its omission of the randomized controlled trial by Dickson et al., the only randomized trial published in gynecologic surgery evaluating ERAS pathways.² This trial compared the length of stay for patients receiving laparotomy for gynecologic cancer surgery who received perioperative care according the ERAS pathway versus those who received standard perioperative care. They found no difference in length of stay – the primary outcome – between the two groups, an impressive 3 days for both. The secondary outcome of postoperative pain was improved for the ERAS group for some of the time points. It was likely that the excellent outcomes in both groups resulted from a Hawthorne effect in which the behavior of study participants is influenced by the fact that they were being observed, in addition to the fact that the physicians involved in the study already were practicing high quality care as part of their “standard” regimen. It simply may be that the act of trying to improve quality is what improves outcomes, not a specific pathway. As senior author, Dr. Peter A. Argenta, explained to me, many of the ERAS elements are “simply good medicine.”

ERAS pathways are an example of process measures of quality. They include elements of care or processes in the delivery of care that are thought to be associated with improved outcomes. Prescription of antibiotics or venous thromboembolism (VTE) prophylaxis are other examples of process measures thought to be associated with improved surgical quality. Rather than rating surgeons’ outcomes (surgical site infection), surgeons are rated on their compliance with a process (the rate of appropriate perioperative antibiotic prescription). However, high compliance with these processes is not automatically associated with improved observed outcomes. For example, hospitals that meet the definition of high quality by virtue of structural measures (such as procedural volume and use of hospital-level quality initiatives) are associated with worse risk-adjusted VTE rates despite demonstrating higher adherence to VTE prophylaxis.³ This is felt to be a function of surveillance bias and the fact that these same hospitals have better capabilities to capture events as part of a feedback mechanism built into their quality initiatives.

What ERAS has favorably done for surgical care is to shine a glaring light on and challenge the unnecessary, old-fashioned, and non–patient-centric interventions that were considered dogma by many. For example, minimizing preoperative fasting is most certainly a patient-friendly adjustment that should absolutely be embraced, regardless of whether or not it speeds up time to discharge. Multimodal approaches to analgesia consistently have been shown to preserve or improve postoperative pain levels with a focus on minimizing opiate use, once again a noble and patient-centered objective.

However, all too many surgical quality interventions focus on their ability to reduce postoperative length of stay. Length of stay is an important driver of health care cost, and an indirect measure of perioperative complications; however, it is not a patient-centered outcome. So long as patients recover from their surgery quickly with respect to pain and function, the location of that recovery (home versus hospital) is less of a focus for most patients. In addition, in the pursuit of shorter hospital stays and less perioperative morbidity, we may encourage practices with unintentional adverse patient-centered outcomes. For example, to preserve a surgeon’s quality metrics, patients who are at high risk for complications may not be offered surgery at all. Long-term ovarian cancer outcomes, such as survival, can be negatively impacted when surgeons opt for less morbid, less radical surgical approaches which have favorable short-term morbidity such as surgical complications and readmissions.⁴

Ultimately we are most likely to see improvement in quality with a complex, nuanced approach to metrics, not simplistic interventions or pathways. We should recognize interventions that are consistently associated with better outcomes such as high procedural volume, consolidating less common procedures to fewer surgeons, data ascertainment, and reporting data to surgeons.⁵ Physicians need to take ownership and involvement in the quality metrics that are created to assess the care we provide. Hospital administrators may not fully understand the confounders, such as comorbidities, that contribute to outcomes, which can lead to mischaracterization, cause unfair comparisons between surgeons, or create unintentional incentives that are not patient-centered.⁶

We all need to understand the epidemiologic science behind evidence-based medicine and to be sophisticated in our ability to review and appraise data so that we can be sensible in what interventions we promote as supported by good evidence. If we fail to correctly identify and characterize what is truly good quality, if we miss the point of what is driving outcomes, or overstate the value of certain interventions, we miss the opportunity to intervene in ways that actually do make a meaningful difference.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no conflicts of interest. Email Dr. Rossi at [email protected].

References

1. Obstet Gynecol 2018;132:e120-e30.

2. Obstet Gynecol. 2017 Feb;129(2):355-62.

3. JAMA. 2013 Oct 9;310(14):1482-9.

4. Gynecol Oncol. 2017 Dec;147(3):607-11.

5. J Am Coll Surg. 2004 Apr;198(4):626-32.

6. Gynecol Oncol. 2018 Oct;151(1):141-4.

Quality in medicine is a peculiar thing. It is clearly apparent, and yet, can be very difficult to measure and quantify. Surgery, a performance art of sorts, can be even more challenging to qualify or rate. However, as a means to elevate the quality of care for all patients, hospital systems and care providers have aggressively made attempts to do so. This is a noble objective.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

In September 2018, the Committee of Gynecologic Practice of the American College of Obstetricians and Gynecologists released ACOG Committee Opinion Number 750, titled, “Perioperative Pathways: Enhanced Recovery After Surgery.”¹

The goals of this committee opinion were to advocate for gynecologic surgeons using the “ERAS” pathways in their perioperative care as part of an evidenced-based approach to quality improvement. ERAS pathways have been previously discussed in this column and feature bundled perioperative pathways that incorporate various concepts such as avoidance of prolonged preoperative fasting, early postoperative feeding, multimodal analgesia (with an avoidance of opiates), and inclusion of antibiotic and antiembolic prophylaxis, among other elements.

What was alarming upon closer review of this ACOG Committee Opinion was its omission of the randomized controlled trial by Dickson et al., the only randomized trial published in gynecologic surgery evaluating ERAS pathways.² This trial compared the length of stay for patients receiving laparotomy for gynecologic cancer surgery who received perioperative care according the ERAS pathway versus those who received standard perioperative care. They found no difference in length of stay – the primary outcome – between the two groups, an impressive 3 days for both. The secondary outcome of postoperative pain was improved for the ERAS group for some of the time points. It was likely that the excellent outcomes in both groups resulted from a Hawthorne effect in which the behavior of study participants is influenced by the fact that they were being observed, in addition to the fact that the physicians involved in the study already were practicing high quality care as part of their “standard” regimen. It simply may be that the act of trying to improve quality is what improves outcomes, not a specific pathway. As senior author, Dr. Peter A. Argenta, explained to me, many of the ERAS elements are “simply good medicine.”

ERAS pathways are an example of process measures of quality. They include elements of care or processes in the delivery of care that are thought to be associated with improved outcomes. Prescription of antibiotics or venous thromboembolism (VTE) prophylaxis are other examples of process measures thought to be associated with improved surgical quality. Rather than rating surgeons’ outcomes (surgical site infection), surgeons are rated on their compliance with a process (the rate of appropriate perioperative antibiotic prescription). However, high compliance with these processes is not automatically associated with improved observed outcomes. For example, hospitals that meet the definition of high quality by virtue of structural measures (such as procedural volume and use of hospital-level quality initiatives) are associated with worse risk-adjusted VTE rates despite demonstrating higher adherence to VTE prophylaxis.³ This is felt to be a function of surveillance bias and the fact that these same hospitals have better capabilities to capture events as part of a feedback mechanism built into their quality initiatives.

What ERAS has favorably done for surgical care is to shine a glaring light on and challenge the unnecessary, old-fashioned, and non–patient-centric interventions that were considered dogma by many. For example, minimizing preoperative fasting is most certainly a patient-friendly adjustment that should absolutely be embraced, regardless of whether or not it speeds up time to discharge. Multimodal approaches to analgesia consistently have been shown to preserve or improve postoperative pain levels with a focus on minimizing opiate use, once again a noble and patient-centered objective.

However, all too many surgical quality interventions focus on their ability to reduce postoperative length of stay. Length of stay is an important driver of health care cost, and an indirect measure of perioperative complications; however, it is not a patient-centered outcome. So long as patients recover from their surgery quickly with respect to pain and function, the location of that recovery (home versus hospital) is less of a focus for most patients. In addition, in the pursuit of shorter hospital stays and less perioperative morbidity, we may encourage practices with unintentional adverse patient-centered outcomes. For example, to preserve a surgeon’s quality metrics, patients who are at high risk for complications may not be offered surgery at all. Long-term ovarian cancer outcomes, such as survival, can be negatively impacted when surgeons opt for less morbid, less radical surgical approaches which have favorable short-term morbidity such as surgical complications and readmissions.⁴

Ultimately we are most likely to see improvement in quality with a complex, nuanced approach to metrics, not simplistic interventions or pathways. We should recognize interventions that are consistently associated with better outcomes such as high procedural volume, consolidating less common procedures to fewer surgeons, data ascertainment, and reporting data to surgeons.⁵ Physicians need to take ownership and involvement in the quality metrics that are created to assess the care we provide. Hospital administrators may not fully understand the confounders, such as comorbidities, that contribute to outcomes, which can lead to mischaracterization, cause unfair comparisons between surgeons, or create unintentional incentives that are not patient-centered.⁶

We all need to understand the epidemiologic science behind evidence-based medicine and to be sophisticated in our ability to review and appraise data so that we can be sensible in what interventions we promote as supported by good evidence. If we fail to correctly identify and characterize what is truly good quality, if we miss the point of what is driving outcomes, or overstate the value of certain interventions, we miss the opportunity to intervene in ways that actually do make a meaningful difference.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no conflicts of interest. Email Dr. Rossi at [email protected].

References

1. Obstet Gynecol 2018;132:e120-e30.

2. Obstet Gynecol. 2017 Feb;129(2):355-62.

3. JAMA. 2013 Oct 9;310(14):1482-9.

4. Gynecol Oncol. 2017 Dec;147(3):607-11.

5. J Am Coll Surg. 2004 Apr;198(4):626-32.

6. Gynecol Oncol. 2018 Oct;151(1):141-4.

Quality in medicine is a peculiar thing. It is clearly apparent, and yet, can be very difficult to measure and quantify. Surgery, a performance art of sorts, can be even more challenging to qualify or rate. However, as a means to elevate the quality of care for all patients, hospital systems and care providers have aggressively made attempts to do so. This is a noble objective.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

In September 2018, the Committee of Gynecologic Practice of the American College of Obstetricians and Gynecologists released ACOG Committee Opinion Number 750, titled, “Perioperative Pathways: Enhanced Recovery After Surgery.”¹

The goals of this committee opinion were to advocate for gynecologic surgeons using the “ERAS” pathways in their perioperative care as part of an evidenced-based approach to quality improvement. ERAS pathways have been previously discussed in this column and feature bundled perioperative pathways that incorporate various concepts such as avoidance of prolonged preoperative fasting, early postoperative feeding, multimodal analgesia (with an avoidance of opiates), and inclusion of antibiotic and antiembolic prophylaxis, among other elements.

What was alarming upon closer review of this ACOG Committee Opinion was its omission of the randomized controlled trial by Dickson et al., the only randomized trial published in gynecologic surgery evaluating ERAS pathways.² This trial compared the length of stay for patients receiving laparotomy for gynecologic cancer surgery who received perioperative care according the ERAS pathway versus those who received standard perioperative care. They found no difference in length of stay – the primary outcome – between the two groups, an impressive 3 days for both. The secondary outcome of postoperative pain was improved for the ERAS group for some of the time points. It was likely that the excellent outcomes in both groups resulted from a Hawthorne effect in which the behavior of study participants is influenced by the fact that they were being observed, in addition to the fact that the physicians involved in the study already were practicing high quality care as part of their “standard” regimen. It simply may be that the act of trying to improve quality is what improves outcomes, not a specific pathway. As senior author, Dr. Peter A. Argenta, explained to me, many of the ERAS elements are “simply good medicine.”

ERAS pathways are an example of process measures of quality. They include elements of care or processes in the delivery of care that are thought to be associated with improved outcomes. Prescription of antibiotics or venous thromboembolism (VTE) prophylaxis are other examples of process measures thought to be associated with improved surgical quality. Rather than rating surgeons’ outcomes (surgical site infection), surgeons are rated on their compliance with a process (the rate of appropriate perioperative antibiotic prescription). However, high compliance with these processes is not automatically associated with improved observed outcomes. For example, hospitals that meet the definition of high quality by virtue of structural measures (such as procedural volume and use of hospital-level quality initiatives) are associated with worse risk-adjusted VTE rates despite demonstrating higher adherence to VTE prophylaxis.³ This is felt to be a function of surveillance bias and the fact that these same hospitals have better capabilities to capture events as part of a feedback mechanism built into their quality initiatives.

What ERAS has favorably done for surgical care is to shine a glaring light on and challenge the unnecessary, old-fashioned, and non–patient-centric interventions that were considered dogma by many. For example, minimizing preoperative fasting is most certainly a patient-friendly adjustment that should absolutely be embraced, regardless of whether or not it speeds up time to discharge. Multimodal approaches to analgesia consistently have been shown to preserve or improve postoperative pain levels with a focus on minimizing opiate use, once again a noble and patient-centered objective.

However, all too many surgical quality interventions focus on their ability to reduce postoperative length of stay. Length of stay is an important driver of health care cost, and an indirect measure of perioperative complications; however, it is not a patient-centered outcome. So long as patients recover from their surgery quickly with respect to pain and function, the location of that recovery (home versus hospital) is less of a focus for most patients. In addition, in the pursuit of shorter hospital stays and less perioperative morbidity, we may encourage practices with unintentional adverse patient-centered outcomes. For example, to preserve a surgeon’s quality metrics, patients who are at high risk for complications may not be offered surgery at all. Long-term ovarian cancer outcomes, such as survival, can be negatively impacted when surgeons opt for less morbid, less radical surgical approaches which have favorable short-term morbidity such as surgical complications and readmissions.⁴

Ultimately we are most likely to see improvement in quality with a complex, nuanced approach to metrics, not simplistic interventions or pathways. We should recognize interventions that are consistently associated with better outcomes such as high procedural volume, consolidating less common procedures to fewer surgeons, data ascertainment, and reporting data to surgeons.⁵ Physicians need to take ownership and involvement in the quality metrics that are created to assess the care we provide. Hospital administrators may not fully understand the confounders, such as comorbidities, that contribute to outcomes, which can lead to mischaracterization, cause unfair comparisons between surgeons, or create unintentional incentives that are not patient-centered.⁶

We all need to understand the epidemiologic science behind evidence-based medicine and to be sophisticated in our ability to review and appraise data so that we can be sensible in what interventions we promote as supported by good evidence. If we fail to correctly identify and characterize what is truly good quality, if we miss the point of what is driving outcomes, or overstate the value of certain interventions, we miss the opportunity to intervene in ways that actually do make a meaningful difference.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no conflicts of interest. Email Dr. Rossi at [email protected].

References

1. Obstet Gynecol 2018;132:e120-e30.

2. Obstet Gynecol. 2017 Feb;129(2):355-62.

3. JAMA. 2013 Oct 9;310(14):1482-9.

4. Gynecol Oncol. 2017 Dec;147(3):607-11.

5. J Am Coll Surg. 2004 Apr;198(4):626-32.

6. Gynecol Oncol. 2018 Oct;151(1):141-4.

Single-nucleotide polymorphisms linked to increased bleeding risk have been identified in patients of African descent taking warfarin, investigators have reported.

Four single-nucleotide polymorphisms (SNPs) were associated with increased major bleeding risk in African Americans at an international normalized ratio (INR) of less than 4, according to results of their preliminary, retrospective study.

The preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University, Chicago, and her coauthors.

“Identifying these variants may help physicians make safer choices in anticoagulation therapy for this understudied patient population,” Dr. Perera and her colleagues wrote in JAMA.

Most prior studies looking at warfarin-related bleeding risk have included predominantly white patients and don’t account for differences in warfarin responsiveness between ethnic groups, they wrote.

Moreover, bleeding-associated SNPs have been identified, but in populations of European ancestry, they added.

The report covered results of a discovery cohort based on African American patients from a genome-wide study conducted at the University of Chicago, and a replication cohort based on patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her coinvestigators found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding, including rs115112393, rs16871327, rs78132896, and rs114504854. In particular, the rs78132896 SNP was found in 35.5% of cases (n = 11) and just 4.9% of controls (n = 9), with an odds ratio of 8.31 (95% confidence interval, 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. That SNP was similarly found in 35.0% of cases (n = 14) and 4.8% of controls (n = 7), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” said the investigators, who reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription, results of gene assay analyses further showed.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” they said.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

SOURCE: Perera MA et al. JAMA. 2018 Oct 23. doi: 10.1001/jama.2018.14955.

Single-nucleotide polymorphisms linked to increased bleeding risk have been identified in patients of African descent taking warfarin, investigators have reported.

Four single-nucleotide polymorphisms (SNPs) were associated with increased major bleeding risk in African Americans at an international normalized ratio (INR) of less than 4, according to results of their preliminary, retrospective study.

The preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University, Chicago, and her coauthors.

“Identifying these variants may help physicians make safer choices in anticoagulation therapy for this understudied patient population,” Dr. Perera and her colleagues wrote in JAMA.

Most prior studies looking at warfarin-related bleeding risk have included predominantly white patients and don’t account for differences in warfarin responsiveness between ethnic groups, they wrote.

Moreover, bleeding-associated SNPs have been identified, but in populations of European ancestry, they added.

The report covered results of a discovery cohort based on African American patients from a genome-wide study conducted at the University of Chicago, and a replication cohort based on patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her coinvestigators found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding, including rs115112393, rs16871327, rs78132896, and rs114504854. In particular, the rs78132896 SNP was found in 35.5% of cases (n = 11) and just 4.9% of controls (n = 9), with an odds ratio of 8.31 (95% confidence interval, 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. That SNP was similarly found in 35.0% of cases (n = 14) and 4.8% of controls (n = 7), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” said the investigators, who reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription, results of gene assay analyses further showed.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” they said.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

SOURCE: Perera MA et al. JAMA. 2018 Oct 23. doi: 10.1001/jama.2018.14955.

Single-nucleotide polymorphisms linked to increased bleeding risk have been identified in patients of African descent taking warfarin, investigators have reported.

Four single-nucleotide polymorphisms (SNPs) were associated with increased major bleeding risk in African Americans at an international normalized ratio (INR) of less than 4, according to results of their preliminary, retrospective study.

The preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University, Chicago, and her coauthors.

“Identifying these variants may help physicians make safer choices in anticoagulation therapy for this understudied patient population,” Dr. Perera and her colleagues wrote in JAMA.

Most prior studies looking at warfarin-related bleeding risk have included predominantly white patients and don’t account for differences in warfarin responsiveness between ethnic groups, they wrote.

Moreover, bleeding-associated SNPs have been identified, but in populations of European ancestry, they added.

The report covered results of a discovery cohort based on African American patients from a genome-wide study conducted at the University of Chicago, and a replication cohort based on patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her coinvestigators found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding, including rs115112393, rs16871327, rs78132896, and rs114504854. In particular, the rs78132896 SNP was found in 35.5% of cases (n = 11) and just 4.9% of controls (n = 9), with an odds ratio of 8.31 (95% confidence interval, 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. That SNP was similarly found in 35.0% of cases (n = 14) and 4.8% of controls (n = 7), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” said the investigators, who reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription, results of gene assay analyses further showed.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” they said.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

SOURCE: Perera MA et al. JAMA. 2018 Oct 23. doi: 10.1001/jama.2018.14955.

TORONTO – Prophylactic cranial irradiation, which is standard-of-care practice in patients with small cell lung cancer, also appears to improve intracranial progression-free survival (iPFS) and overall survival in patients with stage IV non–small cell lung cancer (NSCLC), according to findings from a randomized study.

The cumulative incidence of brain metastases at 2 years was 22% in 41 patients who received prophylactic cranial irradiation (PCI), compared with 52% in 43 patients who received standard care with first- and second-generation tyrosine kinase inhibitors (TKIs) without PCI, Oscar Arrieta, MD, reported at the World Conference on Lung Cancer.

PCI was associated with lower odds of progression to the CNS (odds ratio, 0.16), Dr. Arrieta, of the National Cancer Institute of Mexico, Mexico City, said at the meeting sponsored by the International Association for the Study of Lung Cancer. Further, the relative risk for iPFS in patients with an epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase mutation (ALK), who comprised 70% of patients in both groups, was 0.29 with PCI.

Median overall survival in the groups was 42.8 months versus 25.9 months (HR, 0.48).

The burden of brain metastases can impact the quality and length of survival in patients with NSCLC, and because of an aging population and advances in detection and treatment of primary cancers, patients are living longer and thus are more likely to experience brain metastases, Dr. Arrieta said, noting that this is particularly true for patients at high risk, such as those with elevated carcinoembryonic antigen levels.

Although PCI is standard in small cell lung cancer, its role in NSCLC remains controversial because of concerns about neurologic morbidity and lack of overall survival benefit, he explained.

“The objective of this study was to determine if the use of PCI reduced the development of brain metastases and improved the survival in this population without impairing quality of life,” he said.

Study participants were patients with confirmed stage IV NSCLC and adenocarcinoma histology at high risk for developing brain metastasis. PCI in the treatment group was delivered at 25 Gy/10 fractions.

The findings suggest that in NSCLC with a high risk of developing brain metastases who are treated with a first- or second-generation TKI – particularly those with EGFR and ALK mutations – PCI increases iPFS, Dr. Arrieta said.

“The findings can be extrapolated to those treated with third-generation TKIs, which have higher CNS penetration,” he said, noting, however, that access to third-generation TKIs is limited in most developing countries and cost barriers are high.

Of note, the relatively low dose of PCI used in this study was not associated with significant differences in Mini-Mental State Examination or quality of life scores in the short-term. Long-term assessments are needed, he said, concluding that, while additional study is needed to confirm the findings, the results, including the overall survival benefit seen with PCI, “highlight the benefits of this approach, particularly among patients with a high risk of developing brain metastases.”

Invited discussant Nasser Hanna, MD, the Tom and Julie Wood Family Foundation Professor of Lung Cancer Clinical Research at Indiana University, Indianapolis, said the findings of this “interesting and important study,” are intriguing, but agreed that additional study is needed.

“The study is far too small ... to definitively make this conclusion [that PCI improves iPFS in this population]; I would not recommend PCI without confirmatory data from larger, randomized trials,” he said.

Dr. Arrieta reported advisory roles or provision of expert testimony for Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche, Merck, Takeda, and Bristol-Myers Squibb, and receipt of honoraria and/or research funding from AstraZeneca, Boehringer Ingelheim, Merck, Roche, and Bristol-Myers Squibb. Dr. Nasser reported receiving research grants from Bristol-Myers Squibb, AstraZeneca, Genentech, and Merck.

SOURCE: Arrieta O et al. WCLC 2018, Abstract MA08.02.

TORONTO – Prophylactic cranial irradiation, which is standard-of-care practice in patients with small cell lung cancer, also appears to improve intracranial progression-free survival (iPFS) and overall survival in patients with stage IV non–small cell lung cancer (NSCLC), according to findings from a randomized study.

The cumulative incidence of brain metastases at 2 years was 22% in 41 patients who received prophylactic cranial irradiation (PCI), compared with 52% in 43 patients who received standard care with first- and second-generation tyrosine kinase inhibitors (TKIs) without PCI, Oscar Arrieta, MD, reported at the World Conference on Lung Cancer.

PCI was associated with lower odds of progression to the CNS (odds ratio, 0.16), Dr. Arrieta, of the National Cancer Institute of Mexico, Mexico City, said at the meeting sponsored by the International Association for the Study of Lung Cancer. Further, the relative risk for iPFS in patients with an epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase mutation (ALK), who comprised 70% of patients in both groups, was 0.29 with PCI.

Median overall survival in the groups was 42.8 months versus 25.9 months (HR, 0.48).

The burden of brain metastases can impact the quality and length of survival in patients with NSCLC, and because of an aging population and advances in detection and treatment of primary cancers, patients are living longer and thus are more likely to experience brain metastases, Dr. Arrieta said, noting that this is particularly true for patients at high risk, such as those with elevated carcinoembryonic antigen levels.

Although PCI is standard in small cell lung cancer, its role in NSCLC remains controversial because of concerns about neurologic morbidity and lack of overall survival benefit, he explained.

“The objective of this study was to determine if the use of PCI reduced the development of brain metastases and improved the survival in this population without impairing quality of life,” he said.

Study participants were patients with confirmed stage IV NSCLC and adenocarcinoma histology at high risk for developing brain metastasis. PCI in the treatment group was delivered at 25 Gy/10 fractions.

The findings suggest that in NSCLC with a high risk of developing brain metastases who are treated with a first- or second-generation TKI – particularly those with EGFR and ALK mutations – PCI increases iPFS, Dr. Arrieta said.

“The findings can be extrapolated to those treated with third-generation TKIs, which have higher CNS penetration,” he said, noting, however, that access to third-generation TKIs is limited in most developing countries and cost barriers are high.

Of note, the relatively low dose of PCI used in this study was not associated with significant differences in Mini-Mental State Examination or quality of life scores in the short-term. Long-term assessments are needed, he said, concluding that, while additional study is needed to confirm the findings, the results, including the overall survival benefit seen with PCI, “highlight the benefits of this approach, particularly among patients with a high risk of developing brain metastases.”

Invited discussant Nasser Hanna, MD, the Tom and Julie Wood Family Foundation Professor of Lung Cancer Clinical Research at Indiana University, Indianapolis, said the findings of this “interesting and important study,” are intriguing, but agreed that additional study is needed.

“The study is far too small ... to definitively make this conclusion [that PCI improves iPFS in this population]; I would not recommend PCI without confirmatory data from larger, randomized trials,” he said.

Dr. Arrieta reported advisory roles or provision of expert testimony for Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche, Merck, Takeda, and Bristol-Myers Squibb, and receipt of honoraria and/or research funding from AstraZeneca, Boehringer Ingelheim, Merck, Roche, and Bristol-Myers Squibb. Dr. Nasser reported receiving research grants from Bristol-Myers Squibb, AstraZeneca, Genentech, and Merck.

SOURCE: Arrieta O et al. WCLC 2018, Abstract MA08.02.

TORONTO – Prophylactic cranial irradiation, which is standard-of-care practice in patients with small cell lung cancer, also appears to improve intracranial progression-free survival (iPFS) and overall survival in patients with stage IV non–small cell lung cancer (NSCLC), according to findings from a randomized study.

The cumulative incidence of brain metastases at 2 years was 22% in 41 patients who received prophylactic cranial irradiation (PCI), compared with 52% in 43 patients who received standard care with first- and second-generation tyrosine kinase inhibitors (TKIs) without PCI, Oscar Arrieta, MD, reported at the World Conference on Lung Cancer.

PCI was associated with lower odds of progression to the CNS (odds ratio, 0.16), Dr. Arrieta, of the National Cancer Institute of Mexico, Mexico City, said at the meeting sponsored by the International Association for the Study of Lung Cancer. Further, the relative risk for iPFS in patients with an epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase mutation (ALK), who comprised 70% of patients in both groups, was 0.29 with PCI.

Median overall survival in the groups was 42.8 months versus 25.9 months (HR, 0.48).

The burden of brain metastases can impact the quality and length of survival in patients with NSCLC, and because of an aging population and advances in detection and treatment of primary cancers, patients are living longer and thus are more likely to experience brain metastases, Dr. Arrieta said, noting that this is particularly true for patients at high risk, such as those with elevated carcinoembryonic antigen levels.

Although PCI is standard in small cell lung cancer, its role in NSCLC remains controversial because of concerns about neurologic morbidity and lack of overall survival benefit, he explained.

“The objective of this study was to determine if the use of PCI reduced the development of brain metastases and improved the survival in this population without impairing quality of life,” he said.

Study participants were patients with confirmed stage IV NSCLC and adenocarcinoma histology at high risk for developing brain metastasis. PCI in the treatment group was delivered at 25 Gy/10 fractions.

The findings suggest that in NSCLC with a high risk of developing brain metastases who are treated with a first- or second-generation TKI – particularly those with EGFR and ALK mutations – PCI increases iPFS, Dr. Arrieta said.

“The findings can be extrapolated to those treated with third-generation TKIs, which have higher CNS penetration,” he said, noting, however, that access to third-generation TKIs is limited in most developing countries and cost barriers are high.

Of note, the relatively low dose of PCI used in this study was not associated with significant differences in Mini-Mental State Examination or quality of life scores in the short-term. Long-term assessments are needed, he said, concluding that, while additional study is needed to confirm the findings, the results, including the overall survival benefit seen with PCI, “highlight the benefits of this approach, particularly among patients with a high risk of developing brain metastases.”

Invited discussant Nasser Hanna, MD, the Tom and Julie Wood Family Foundation Professor of Lung Cancer Clinical Research at Indiana University, Indianapolis, said the findings of this “interesting and important study,” are intriguing, but agreed that additional study is needed.

“The study is far too small ... to definitively make this conclusion [that PCI improves iPFS in this population]; I would not recommend PCI without confirmatory data from larger, randomized trials,” he said.

Dr. Arrieta reported advisory roles or provision of expert testimony for Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche, Merck, Takeda, and Bristol-Myers Squibb, and receipt of honoraria and/or research funding from AstraZeneca, Boehringer Ingelheim, Merck, Roche, and Bristol-Myers Squibb. Dr. Nasser reported receiving research grants from Bristol-Myers Squibb, AstraZeneca, Genentech, and Merck.

SOURCE: Arrieta O et al. WCLC 2018, Abstract MA08.02.