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From the Washington Office: An opportunity to address policymakers on the concerns of Fellows
On March 15, 2018, I had the opportunity to present on behalf of the ACS at a roundtable discussion on Capitol Hill to members of the House Ways and Means Committee on the topic of Medicare red tape relief
The roundtable provided members of this key committee of jurisdiction over Medicare policy the opportunity to hear from representatives from a variety of health care professional organizations on how Congress can improve Medicare to work more effectively and efficiently for both patients and providers. Each group was allotted just three minutes for their presentation. A summary of my presentation is included below:
E/M Documentation Guidelines
The ACS has significant concerns regarding Evaluation and Management (E/M) Documentation Guidelines. Though CMS created the E/M documentation guidelines 23 years ago with the laudable goal of adding structure to the various levels of E/M services, and in an effort to create a sense of equivalency of E/M services across the multitude of specialties, ACS believes the time has come to re-examine and revise these guidelines to be more appropriate in the modern digital information era.
Again, the primary goal of all medical record documentation is to provide an accurate, chronologic record of patient care. That said, the medical record also serves other important goals including communication between providers, data exchange to facilitate clinical decisions, and a legal document. The payment-focused E/M documentation guidelines do not serve any of these objectives.
There must be some level of trust of the provider by the payers. Physicians should have the ability to meet the primary goal of the medical record without being required to repeatedly enter the same information. If a family history is recorded on Monday, there should be no requirement to re-record it on Thursday unless something cogent changes in the interim. ACS believes that documentation should focus on the minimum data elements needed to establish an accurate chronologic record of patient care.
The ACS is prepared to assist in an effort to explore ways to revise the current paper-based E/M documentation guidelines such that they more efficiently and accurately document patient care information in the modern digital era.
Meaningful Measurement of Surgical Quality
I also addressed concerns relative to the meaningful measurement of surgical quality. Despite having expended significant human and financial resources toward helping Fellows succeed in MIPS, the College is becoming increasingly concerned that MIPS is not actually measuring surgical quality, and therefore, is not a quality program for surgery and serves primarily as a payment program.
As evidence, the most recent quality metric data available (from the 2015 Physician Quality Reporting System) show that many of the CMS quality measures reported by surgeons have little to do with improving the quality of the actual surgical care provided to patients. For general surgeons, the two most commonly reported measures were the documentation of a patient’s medications in the medical record and tobacco use screening. While no one would deny the importance of either of these activities, neither is of much real value in the effort to measure the quality of surgical care provided. In another, perhaps even more illustrative example, one of the most common quality measures reported by urologists was inquiring of their patients whether they had received a pneumovax. This obviously has little to do with why one would see an urologist, much less the quality of care provided.
As an organization, the ACS and its members are absolutely dedicated to improving the quality of care they provide to their patients. However, the quality measures forming the basis of the assessment of their care must first be relevant to the surgical care they provide, and second be achievable. Fellows are increasingly expressing concerns about the burdens imposed by the Quality component of MIPS and believe their efforts to participate do little to meaningfully measure the quality of surgical care they provide. I asked that the Ways and Means Committee hold a hearing specifically addressing issues relative to the Quality component of MIPS.
Standardizing Electronic Prior Authorization for Safe Prescribing Act
I expressed ACS’ support for the Standardizing Electronic Prior Authorization for Safe Prescribing Act, H.R. 4841, which would allow for electronic prior authorization under Medicare Part D and allow for the creation of technical standards for the electronic transmission of prior authorization. While the College believes this legislation is a good first step for electronic prior authorization, I asked that the scope of the legislation be expanded to include all medical services, supplies, and prescription drugs covered by the Medicare program, and also requested prior authorization policies be standardized across all insurers and that prior authorization requests, decisions, and appeals processes be automated through uniform electronic transaction portals for all services and supplies.
As evidence, I provided data from a 2017 ACS survey of nearly 300 surgeons and their staff, which indicated that, on average, a medical practice receives approximately 37 prior authorization requests per provider, per week. Action on these requests requires 25 hours to complete. This exorbitant expenditure of time and resources required for prior authorization is largely due to a lack of automated prior authorization processes that integrate with current electronic health record systems. The ACS is committed to working with the bill’s sponsors and the Ways and Means Committee toward a goal of swift passage.
Questions from and discussion with members of the Ways and Means Committee were truncated because of votes on the House floor. We look forward to continuing the dialogue in the coming weeks when the roundtable is reconvened.
Until next month ….
On March 15, 2018, I had the opportunity to present on behalf of the ACS at a roundtable discussion on Capitol Hill to members of the House Ways and Means Committee on the topic of Medicare red tape relief
The roundtable provided members of this key committee of jurisdiction over Medicare policy the opportunity to hear from representatives from a variety of health care professional organizations on how Congress can improve Medicare to work more effectively and efficiently for both patients and providers. Each group was allotted just three minutes for their presentation. A summary of my presentation is included below:
E/M Documentation Guidelines
The ACS has significant concerns regarding Evaluation and Management (E/M) Documentation Guidelines. Though CMS created the E/M documentation guidelines 23 years ago with the laudable goal of adding structure to the various levels of E/M services, and in an effort to create a sense of equivalency of E/M services across the multitude of specialties, ACS believes the time has come to re-examine and revise these guidelines to be more appropriate in the modern digital information era.
Again, the primary goal of all medical record documentation is to provide an accurate, chronologic record of patient care. That said, the medical record also serves other important goals including communication between providers, data exchange to facilitate clinical decisions, and a legal document. The payment-focused E/M documentation guidelines do not serve any of these objectives.
There must be some level of trust of the provider by the payers. Physicians should have the ability to meet the primary goal of the medical record without being required to repeatedly enter the same information. If a family history is recorded on Monday, there should be no requirement to re-record it on Thursday unless something cogent changes in the interim. ACS believes that documentation should focus on the minimum data elements needed to establish an accurate chronologic record of patient care.
The ACS is prepared to assist in an effort to explore ways to revise the current paper-based E/M documentation guidelines such that they more efficiently and accurately document patient care information in the modern digital era.
Meaningful Measurement of Surgical Quality
I also addressed concerns relative to the meaningful measurement of surgical quality. Despite having expended significant human and financial resources toward helping Fellows succeed in MIPS, the College is becoming increasingly concerned that MIPS is not actually measuring surgical quality, and therefore, is not a quality program for surgery and serves primarily as a payment program.
As evidence, the most recent quality metric data available (from the 2015 Physician Quality Reporting System) show that many of the CMS quality measures reported by surgeons have little to do with improving the quality of the actual surgical care provided to patients. For general surgeons, the two most commonly reported measures were the documentation of a patient’s medications in the medical record and tobacco use screening. While no one would deny the importance of either of these activities, neither is of much real value in the effort to measure the quality of surgical care provided. In another, perhaps even more illustrative example, one of the most common quality measures reported by urologists was inquiring of their patients whether they had received a pneumovax. This obviously has little to do with why one would see an urologist, much less the quality of care provided.
As an organization, the ACS and its members are absolutely dedicated to improving the quality of care they provide to their patients. However, the quality measures forming the basis of the assessment of their care must first be relevant to the surgical care they provide, and second be achievable. Fellows are increasingly expressing concerns about the burdens imposed by the Quality component of MIPS and believe their efforts to participate do little to meaningfully measure the quality of surgical care they provide. I asked that the Ways and Means Committee hold a hearing specifically addressing issues relative to the Quality component of MIPS.
Standardizing Electronic Prior Authorization for Safe Prescribing Act
I expressed ACS’ support for the Standardizing Electronic Prior Authorization for Safe Prescribing Act, H.R. 4841, which would allow for electronic prior authorization under Medicare Part D and allow for the creation of technical standards for the electronic transmission of prior authorization. While the College believes this legislation is a good first step for electronic prior authorization, I asked that the scope of the legislation be expanded to include all medical services, supplies, and prescription drugs covered by the Medicare program, and also requested prior authorization policies be standardized across all insurers and that prior authorization requests, decisions, and appeals processes be automated through uniform electronic transaction portals for all services and supplies.
As evidence, I provided data from a 2017 ACS survey of nearly 300 surgeons and their staff, which indicated that, on average, a medical practice receives approximately 37 prior authorization requests per provider, per week. Action on these requests requires 25 hours to complete. This exorbitant expenditure of time and resources required for prior authorization is largely due to a lack of automated prior authorization processes that integrate with current electronic health record systems. The ACS is committed to working with the bill’s sponsors and the Ways and Means Committee toward a goal of swift passage.
Questions from and discussion with members of the Ways and Means Committee were truncated because of votes on the House floor. We look forward to continuing the dialogue in the coming weeks when the roundtable is reconvened.
Until next month ….
On March 15, 2018, I had the opportunity to present on behalf of the ACS at a roundtable discussion on Capitol Hill to members of the House Ways and Means Committee on the topic of Medicare red tape relief
The roundtable provided members of this key committee of jurisdiction over Medicare policy the opportunity to hear from representatives from a variety of health care professional organizations on how Congress can improve Medicare to work more effectively and efficiently for both patients and providers. Each group was allotted just three minutes for their presentation. A summary of my presentation is included below:
E/M Documentation Guidelines
The ACS has significant concerns regarding Evaluation and Management (E/M) Documentation Guidelines. Though CMS created the E/M documentation guidelines 23 years ago with the laudable goal of adding structure to the various levels of E/M services, and in an effort to create a sense of equivalency of E/M services across the multitude of specialties, ACS believes the time has come to re-examine and revise these guidelines to be more appropriate in the modern digital information era.
Again, the primary goal of all medical record documentation is to provide an accurate, chronologic record of patient care. That said, the medical record also serves other important goals including communication between providers, data exchange to facilitate clinical decisions, and a legal document. The payment-focused E/M documentation guidelines do not serve any of these objectives.
There must be some level of trust of the provider by the payers. Physicians should have the ability to meet the primary goal of the medical record without being required to repeatedly enter the same information. If a family history is recorded on Monday, there should be no requirement to re-record it on Thursday unless something cogent changes in the interim. ACS believes that documentation should focus on the minimum data elements needed to establish an accurate chronologic record of patient care.
The ACS is prepared to assist in an effort to explore ways to revise the current paper-based E/M documentation guidelines such that they more efficiently and accurately document patient care information in the modern digital era.
Meaningful Measurement of Surgical Quality
I also addressed concerns relative to the meaningful measurement of surgical quality. Despite having expended significant human and financial resources toward helping Fellows succeed in MIPS, the College is becoming increasingly concerned that MIPS is not actually measuring surgical quality, and therefore, is not a quality program for surgery and serves primarily as a payment program.
As evidence, the most recent quality metric data available (from the 2015 Physician Quality Reporting System) show that many of the CMS quality measures reported by surgeons have little to do with improving the quality of the actual surgical care provided to patients. For general surgeons, the two most commonly reported measures were the documentation of a patient’s medications in the medical record and tobacco use screening. While no one would deny the importance of either of these activities, neither is of much real value in the effort to measure the quality of surgical care provided. In another, perhaps even more illustrative example, one of the most common quality measures reported by urologists was inquiring of their patients whether they had received a pneumovax. This obviously has little to do with why one would see an urologist, much less the quality of care provided.
As an organization, the ACS and its members are absolutely dedicated to improving the quality of care they provide to their patients. However, the quality measures forming the basis of the assessment of their care must first be relevant to the surgical care they provide, and second be achievable. Fellows are increasingly expressing concerns about the burdens imposed by the Quality component of MIPS and believe their efforts to participate do little to meaningfully measure the quality of surgical care they provide. I asked that the Ways and Means Committee hold a hearing specifically addressing issues relative to the Quality component of MIPS.
Standardizing Electronic Prior Authorization for Safe Prescribing Act
I expressed ACS’ support for the Standardizing Electronic Prior Authorization for Safe Prescribing Act, H.R. 4841, which would allow for electronic prior authorization under Medicare Part D and allow for the creation of technical standards for the electronic transmission of prior authorization. While the College believes this legislation is a good first step for electronic prior authorization, I asked that the scope of the legislation be expanded to include all medical services, supplies, and prescription drugs covered by the Medicare program, and also requested prior authorization policies be standardized across all insurers and that prior authorization requests, decisions, and appeals processes be automated through uniform electronic transaction portals for all services and supplies.
As evidence, I provided data from a 2017 ACS survey of nearly 300 surgeons and their staff, which indicated that, on average, a medical practice receives approximately 37 prior authorization requests per provider, per week. Action on these requests requires 25 hours to complete. This exorbitant expenditure of time and resources required for prior authorization is largely due to a lack of automated prior authorization processes that integrate with current electronic health record systems. The ACS is committed to working with the bill’s sponsors and the Ways and Means Committee toward a goal of swift passage.
Questions from and discussion with members of the Ways and Means Committee were truncated because of votes on the House floor. We look forward to continuing the dialogue in the coming weeks when the roundtable is reconvened.
Until next month ….
VIDEO: Pelvic radiation surpasses brachytherapy/chemo for early endometrial cancer
NEW ORLEANS – Pelvic radiation was as effective for producing recurrence-free survival as vaginal cuff brachytherapy plus chemotherapy but with less acute toxicity and fewer local recurrences in women with high-risk stage I or stage II endometrial cancer in a multicenter, randomized trial with 601 patients.
These findings should result in wider use of pelvic radiation as the preferred treatment for these patients, Marcus E. Randall, MD, said at the annual meeting of the Society of Gynecologic Oncology. “It will change practice,” he predicted.
Dr. Randall and his colleagues from the Gynecologic Oncology Group (which recently became part of NRG Oncology) designed the trial, GOG-0249, to address recent interest in using vaginal cuff brachytherapy plus chemotherapy with carboplatin and paclitaxel as an alternative to the more standard approach of pelvic radiation for treating women with either high-risk stage I or stage II endometrial cancers. Clinicians had considered the brachytherapy plus chemotherapy approach a reasonable option by “extrapolating from studies with advanced” endometrial cancer, but with no direct evidence to support this alternative, Dr. Randall explained in a video interview.
To generate evidence, the researchers enrolled 601 patients at several participating U.S. centers and followed them for a median of 53 months (4.4 years), with 259 patients treated and followed in the pelvic radiation arm and 268 patients treated and followed in the brachytherapy plus chemotherapy arm. Clinicians administered the complete planned treatment regimen to 91% of patients assigned to pelvic radiation and to 87% of those assigned to brachytherapy plus chemotherapy. Three quarters of enrolled patients had high-risk stage I disease, and the entire study group averaged about 62 years old.
The trial’s primary endpoint was recurrence-free survival, which occurred in 78% of the pelvic radiation patients and 79% of brachytherapy plus chemotherapy patients after 5 years when analyzed on an intention-to-treat basis. The two subgroups also showed similar rates of overall survival during follow-up.
Although the two treatments produced essentially identical outcomes for the primary result, they showed two important differences on secondary outcomes, reported Dr. Randall, professor and chair of radiation medicine at the University of Kentucky in Lexington.
Acute adverse effects rated as grade 3 severity or higher occurred in 11% of the pelvic radiation patients and in 64% of the brachytherapy plus chemotherapy patients, although late toxicities occurred at similar rates (13% and 12%, respectively) in the two subgroups.
Local pelvic and para-aortic nodal recurrences occurred in 4% of the pelvic radiation patients and in 9% of the brachytherapy plus chemotherapy patients, a 53% relative risk reduction with pelvic radiation. The difference in the nodal recurrences was apparent within the first year of follow-up, and the difference in rates continued to steadily widen over time after that. However the rates of both vaginal and distant recurrences were very similar in the two treatment arms. Distant recurrences were the most common type of treatment failure, occurring in about 18% of patients in both subgroups during complete follow-up.
“Pelvic radiation therapy remains an appropriate and preferable treatment for high-risk, early stage endometrial carcinoma,” Dr. Randall concluded.
SOURCE: Randall ME et al. SGO 2018.
NEW ORLEANS – Pelvic radiation was as effective for producing recurrence-free survival as vaginal cuff brachytherapy plus chemotherapy but with less acute toxicity and fewer local recurrences in women with high-risk stage I or stage II endometrial cancer in a multicenter, randomized trial with 601 patients.
These findings should result in wider use of pelvic radiation as the preferred treatment for these patients, Marcus E. Randall, MD, said at the annual meeting of the Society of Gynecologic Oncology. “It will change practice,” he predicted.
Dr. Randall and his colleagues from the Gynecologic Oncology Group (which recently became part of NRG Oncology) designed the trial, GOG-0249, to address recent interest in using vaginal cuff brachytherapy plus chemotherapy with carboplatin and paclitaxel as an alternative to the more standard approach of pelvic radiation for treating women with either high-risk stage I or stage II endometrial cancers. Clinicians had considered the brachytherapy plus chemotherapy approach a reasonable option by “extrapolating from studies with advanced” endometrial cancer, but with no direct evidence to support this alternative, Dr. Randall explained in a video interview.
To generate evidence, the researchers enrolled 601 patients at several participating U.S. centers and followed them for a median of 53 months (4.4 years), with 259 patients treated and followed in the pelvic radiation arm and 268 patients treated and followed in the brachytherapy plus chemotherapy arm. Clinicians administered the complete planned treatment regimen to 91% of patients assigned to pelvic radiation and to 87% of those assigned to brachytherapy plus chemotherapy. Three quarters of enrolled patients had high-risk stage I disease, and the entire study group averaged about 62 years old.
The trial’s primary endpoint was recurrence-free survival, which occurred in 78% of the pelvic radiation patients and 79% of brachytherapy plus chemotherapy patients after 5 years when analyzed on an intention-to-treat basis. The two subgroups also showed similar rates of overall survival during follow-up.
Although the two treatments produced essentially identical outcomes for the primary result, they showed two important differences on secondary outcomes, reported Dr. Randall, professor and chair of radiation medicine at the University of Kentucky in Lexington.
Acute adverse effects rated as grade 3 severity or higher occurred in 11% of the pelvic radiation patients and in 64% of the brachytherapy plus chemotherapy patients, although late toxicities occurred at similar rates (13% and 12%, respectively) in the two subgroups.
Local pelvic and para-aortic nodal recurrences occurred in 4% of the pelvic radiation patients and in 9% of the brachytherapy plus chemotherapy patients, a 53% relative risk reduction with pelvic radiation. The difference in the nodal recurrences was apparent within the first year of follow-up, and the difference in rates continued to steadily widen over time after that. However the rates of both vaginal and distant recurrences were very similar in the two treatment arms. Distant recurrences were the most common type of treatment failure, occurring in about 18% of patients in both subgroups during complete follow-up.
“Pelvic radiation therapy remains an appropriate and preferable treatment for high-risk, early stage endometrial carcinoma,” Dr. Randall concluded.
SOURCE: Randall ME et al. SGO 2018.
NEW ORLEANS – Pelvic radiation was as effective for producing recurrence-free survival as vaginal cuff brachytherapy plus chemotherapy but with less acute toxicity and fewer local recurrences in women with high-risk stage I or stage II endometrial cancer in a multicenter, randomized trial with 601 patients.
These findings should result in wider use of pelvic radiation as the preferred treatment for these patients, Marcus E. Randall, MD, said at the annual meeting of the Society of Gynecologic Oncology. “It will change practice,” he predicted.
Dr. Randall and his colleagues from the Gynecologic Oncology Group (which recently became part of NRG Oncology) designed the trial, GOG-0249, to address recent interest in using vaginal cuff brachytherapy plus chemotherapy with carboplatin and paclitaxel as an alternative to the more standard approach of pelvic radiation for treating women with either high-risk stage I or stage II endometrial cancers. Clinicians had considered the brachytherapy plus chemotherapy approach a reasonable option by “extrapolating from studies with advanced” endometrial cancer, but with no direct evidence to support this alternative, Dr. Randall explained in a video interview.
To generate evidence, the researchers enrolled 601 patients at several participating U.S. centers and followed them for a median of 53 months (4.4 years), with 259 patients treated and followed in the pelvic radiation arm and 268 patients treated and followed in the brachytherapy plus chemotherapy arm. Clinicians administered the complete planned treatment regimen to 91% of patients assigned to pelvic radiation and to 87% of those assigned to brachytherapy plus chemotherapy. Three quarters of enrolled patients had high-risk stage I disease, and the entire study group averaged about 62 years old.
The trial’s primary endpoint was recurrence-free survival, which occurred in 78% of the pelvic radiation patients and 79% of brachytherapy plus chemotherapy patients after 5 years when analyzed on an intention-to-treat basis. The two subgroups also showed similar rates of overall survival during follow-up.
Although the two treatments produced essentially identical outcomes for the primary result, they showed two important differences on secondary outcomes, reported Dr. Randall, professor and chair of radiation medicine at the University of Kentucky in Lexington.
Acute adverse effects rated as grade 3 severity or higher occurred in 11% of the pelvic radiation patients and in 64% of the brachytherapy plus chemotherapy patients, although late toxicities occurred at similar rates (13% and 12%, respectively) in the two subgroups.
Local pelvic and para-aortic nodal recurrences occurred in 4% of the pelvic radiation patients and in 9% of the brachytherapy plus chemotherapy patients, a 53% relative risk reduction with pelvic radiation. The difference in the nodal recurrences was apparent within the first year of follow-up, and the difference in rates continued to steadily widen over time after that. However the rates of both vaginal and distant recurrences were very similar in the two treatment arms. Distant recurrences were the most common type of treatment failure, occurring in about 18% of patients in both subgroups during complete follow-up.
“Pelvic radiation therapy remains an appropriate and preferable treatment for high-risk, early stage endometrial carcinoma,” Dr. Randall concluded.
SOURCE: Randall ME et al. SGO 2018.
REPORTING FROM SGO 2018
Key clinical point:
Major finding: Acute, higher-grade toxicities occurred in 11% of pelvic radiation patients and 64% of brachytherapy/chemotherapy patients.
Study details: GOG-0249, a multicenter, randomized phase III trial with 601 patients.
Disclosures: GOG-0249 had no commercial funding. Dr. Randall had no disclosures.
Source: Randall ME et al. SGO 2018.
Diabetes does its part to increase health care costs
, which was enough to make it “the most costly chronic illness in the country,” the American Diabetes Association said.
The estimated total economic burden of diabetes went from an inflation-adjusted estimate of $261 billion in 2012 to $327 billion – $237 billion in direct medical costs and $90 billion in indirect costs such as absenteeism, reduced productivity, and premature mortality – in 2017, according to a new report from the ADA published in Diabetes Care.
“One of every four health care dollars is incurred by someone with diagnosed diabetes, and one of every seven health care dollars is spent directly treating diabetes and its complications,” the ADA said in a written statement.
The study used data from a large number of sources, including the American Community Survey, the OptumInsight de-identified Normative Health Information database, the Medical Expenditure Panel Survey, and the Medicare 5% sample Standard Analytical Files. All cost estimates were extrapolated to the 2017 U.S. population and adjusted to 2017 dollars.
SOURCE: Diabetes Care. 2018 Mar 22. doi: 10.2337/dci18-0007.
, which was enough to make it “the most costly chronic illness in the country,” the American Diabetes Association said.
The estimated total economic burden of diabetes went from an inflation-adjusted estimate of $261 billion in 2012 to $327 billion – $237 billion in direct medical costs and $90 billion in indirect costs such as absenteeism, reduced productivity, and premature mortality – in 2017, according to a new report from the ADA published in Diabetes Care.
“One of every four health care dollars is incurred by someone with diagnosed diabetes, and one of every seven health care dollars is spent directly treating diabetes and its complications,” the ADA said in a written statement.
The study used data from a large number of sources, including the American Community Survey, the OptumInsight de-identified Normative Health Information database, the Medical Expenditure Panel Survey, and the Medicare 5% sample Standard Analytical Files. All cost estimates were extrapolated to the 2017 U.S. population and adjusted to 2017 dollars.
SOURCE: Diabetes Care. 2018 Mar 22. doi: 10.2337/dci18-0007.
, which was enough to make it “the most costly chronic illness in the country,” the American Diabetes Association said.
The estimated total economic burden of diabetes went from an inflation-adjusted estimate of $261 billion in 2012 to $327 billion – $237 billion in direct medical costs and $90 billion in indirect costs such as absenteeism, reduced productivity, and premature mortality – in 2017, according to a new report from the ADA published in Diabetes Care.
“One of every four health care dollars is incurred by someone with diagnosed diabetes, and one of every seven health care dollars is spent directly treating diabetes and its complications,” the ADA said in a written statement.
The study used data from a large number of sources, including the American Community Survey, the OptumInsight de-identified Normative Health Information database, the Medical Expenditure Panel Survey, and the Medicare 5% sample Standard Analytical Files. All cost estimates were extrapolated to the 2017 U.S. population and adjusted to 2017 dollars.
SOURCE: Diabetes Care. 2018 Mar 22. doi: 10.2337/dci18-0007.
FROM DIABETES CARE
MicroRNAs flag liver damage in HIV-, HCV-infected persons
BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.
An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.
“Our results reveal that HIV-1 infection impacts liver miRNA metabolism and upregulated plasma levels of miRNAs that were previously associated with liver damage, even in the absence of an HCV coinfection,” he said at the Conference on Retroviruses & Opportunistic Infections. He reported the results in a themed discussion and scientific poster session.
Dr. Martinez and his colleagues performed large-scale deep sequencing analyses of miRNAs in plasma from 144 patients with HIV-1 who had elevated alanine aminotransferase (ALT), focal nodular hyperplasia, or HCV coinfections, and compared results with those from healthy blood donors and HCV mono-infected persons.
They identified 1,425 different mature miRNAs in the study samples. Compared with healthy donors, patients with HIV infections showed significantly dysregulated expression of 25 miRNAs, and 19 of these miRNAs were also found in patients with HCV monoinfection. All but 1 of 14 upregulated miRNAs in patients with HCV monoinfections were also upregulated in patients with HIV monoinfections.
Of these 13 upregulated miRNAs, 11 significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels in most of the study samples, including those from healthy donors, Dr. Martinez noted.
“These results indicate that HIV mono-infection is able to dysregulate microRNAs related with liver injury and damage,” he said.
Of the 13 miRNAs, two, labeled miR-99a-5p and miR-100-5p, which belong to the same family of miRNAs, were found to be significantly upregulated in patients with HIV and HCV coinfections that later progressed to liver cirrhosis “even those these patients exhibited no liver fibrosis at the time of sampling,” he said
The two culprit miRNAs were significantly correlated with ALT and AST levels, as well as the degree of liver fibrosis.
A comparison of samples from patients with HIV monoinfection who had elevated ALT or focal nodular hyperplasia with those of patients with HIV infection but normal ALT levels showed that two other miRNAs, miR-122-3p and miR-193b-5p, were highly and significantly upregulated, and correlated with both aminotransferase and liver fibrosis levels.
“This study demonstrates the potential of microRNAs as biomarkers of liver injury progression in HIV-1 infected patients,” Dr. Martinez concluded.
The Spanish Instituto de Salud Carlos III and the Spanish AIDS network funded the study. Dr. Martinez reported having no conflicts of interest.
SOURCE: Martinez MA et al. CROI 2018, abstract 639.
BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.
An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.
“Our results reveal that HIV-1 infection impacts liver miRNA metabolism and upregulated plasma levels of miRNAs that were previously associated with liver damage, even in the absence of an HCV coinfection,” he said at the Conference on Retroviruses & Opportunistic Infections. He reported the results in a themed discussion and scientific poster session.
Dr. Martinez and his colleagues performed large-scale deep sequencing analyses of miRNAs in plasma from 144 patients with HIV-1 who had elevated alanine aminotransferase (ALT), focal nodular hyperplasia, or HCV coinfections, and compared results with those from healthy blood donors and HCV mono-infected persons.
They identified 1,425 different mature miRNAs in the study samples. Compared with healthy donors, patients with HIV infections showed significantly dysregulated expression of 25 miRNAs, and 19 of these miRNAs were also found in patients with HCV monoinfection. All but 1 of 14 upregulated miRNAs in patients with HCV monoinfections were also upregulated in patients with HIV monoinfections.
Of these 13 upregulated miRNAs, 11 significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels in most of the study samples, including those from healthy donors, Dr. Martinez noted.
“These results indicate that HIV mono-infection is able to dysregulate microRNAs related with liver injury and damage,” he said.
Of the 13 miRNAs, two, labeled miR-99a-5p and miR-100-5p, which belong to the same family of miRNAs, were found to be significantly upregulated in patients with HIV and HCV coinfections that later progressed to liver cirrhosis “even those these patients exhibited no liver fibrosis at the time of sampling,” he said
The two culprit miRNAs were significantly correlated with ALT and AST levels, as well as the degree of liver fibrosis.
A comparison of samples from patients with HIV monoinfection who had elevated ALT or focal nodular hyperplasia with those of patients with HIV infection but normal ALT levels showed that two other miRNAs, miR-122-3p and miR-193b-5p, were highly and significantly upregulated, and correlated with both aminotransferase and liver fibrosis levels.
“This study demonstrates the potential of microRNAs as biomarkers of liver injury progression in HIV-1 infected patients,” Dr. Martinez concluded.
The Spanish Instituto de Salud Carlos III and the Spanish AIDS network funded the study. Dr. Martinez reported having no conflicts of interest.
SOURCE: Martinez MA et al. CROI 2018, abstract 639.
BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.
An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.
“Our results reveal that HIV-1 infection impacts liver miRNA metabolism and upregulated plasma levels of miRNAs that were previously associated with liver damage, even in the absence of an HCV coinfection,” he said at the Conference on Retroviruses & Opportunistic Infections. He reported the results in a themed discussion and scientific poster session.
Dr. Martinez and his colleagues performed large-scale deep sequencing analyses of miRNAs in plasma from 144 patients with HIV-1 who had elevated alanine aminotransferase (ALT), focal nodular hyperplasia, or HCV coinfections, and compared results with those from healthy blood donors and HCV mono-infected persons.
They identified 1,425 different mature miRNAs in the study samples. Compared with healthy donors, patients with HIV infections showed significantly dysregulated expression of 25 miRNAs, and 19 of these miRNAs were also found in patients with HCV monoinfection. All but 1 of 14 upregulated miRNAs in patients with HCV monoinfections were also upregulated in patients with HIV monoinfections.
Of these 13 upregulated miRNAs, 11 significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels in most of the study samples, including those from healthy donors, Dr. Martinez noted.
“These results indicate that HIV mono-infection is able to dysregulate microRNAs related with liver injury and damage,” he said.
Of the 13 miRNAs, two, labeled miR-99a-5p and miR-100-5p, which belong to the same family of miRNAs, were found to be significantly upregulated in patients with HIV and HCV coinfections that later progressed to liver cirrhosis “even those these patients exhibited no liver fibrosis at the time of sampling,” he said
The two culprit miRNAs were significantly correlated with ALT and AST levels, as well as the degree of liver fibrosis.
A comparison of samples from patients with HIV monoinfection who had elevated ALT or focal nodular hyperplasia with those of patients with HIV infection but normal ALT levels showed that two other miRNAs, miR-122-3p and miR-193b-5p, were highly and significantly upregulated, and correlated with both aminotransferase and liver fibrosis levels.
“This study demonstrates the potential of microRNAs as biomarkers of liver injury progression in HIV-1 infected patients,” Dr. Martinez concluded.
The Spanish Instituto de Salud Carlos III and the Spanish AIDS network funded the study. Dr. Martinez reported having no conflicts of interest.
SOURCE: Martinez MA et al. CROI 2018, abstract 639.
REPORTING FROM CROI
Key clinical point: Specific circulating microRNAs appear to be biomarkers for liver injury and progression in persons with HIV and/or HCV infections.
Major finding: Two microRNAs correlated with elevated liver enzymes and liver fibrosis in patients with HIV and HCV coinfection, and two correlated with liver injury in patients with HIV monoinfection.
Study details: Analysis of plasma samples from 144 persons with HIV with elevated ALT, focal nodular hyperplasia, or HCV coinfections, with control samples from healthy donors and HCV monoinfected individuals.
Disclosures: The Spanish Instituto de Salud Carlos III and the Spanish AIDS network funded the study. Dr. Martinez reported having no conflicts of interest.
Source: Martinez MA et al. CROI 2018, abstract 639.
April 2018 - What's your diagnosis?
Answer to “What’s your diagnosis?” Chilaiditi syndrome
Abdominal CT images display the Chilaiditi sign, which is the radiographic term used to describe interposition of the colon, usually at the hepatic flexure, with the liver and right diaphragm.1 This is considered an incidental radiographic finding and is generally asymptomatic; however, when one develops clinical symptoms such as abdominal pain, bloating or distension, anorexia, constipation, or nausea it is called Chilaiditi syndrome.
First described by Greek radiologist Demetrius Chilaiditi in 1910, Chilaiditi syndrome is a rare occurrence with an incidence rate of 0.25%-0.28% in the general population.2 The etiology of Chilaiditi syndrome is felt to be congenital or acquired with predisposing congenital abnormalities such as absent suspensory or falciform ligaments, redundant colon, malposition of the colon, dolichocolon, and paralysis of the right diaphragm. Other risk factors for development of Chilaiditi syndrome include chronic constipation, cirrhosis, ascites, and obesity. Men are times times as likely as women to develop Chilaiditi syndrome and it is more common in the elderly, occurring in 1% of the elderly population.3 Chilaiditi sign is diagnosed with radiographic imaging meeting the following criteria: the right hemidiaphragm must be elevated above the liver by the intestine, the bowel must be distended by air to illustrate pseudopneumoperitoneum, and the superior margin of the liver must be depressed below the level of the left hemidiaphragm.1
Chilaiditi syndrome is managed conservatively with close observation. Recurrent symptoms can be treated with colopexy. This syndrome has been known to cause severe complications including volvulus of the cecum, splenic flexure, or transverse colon, cecal perforation, and subdiaphragmatic perforated appendicitis, which all require surgical intervention.3 It is important to recognize Chilaiditi syndrome on presentation to prevent unnecessary diagnostic studies and unwarranted surgical intervention.
References
1. Uygungul, E., Uygungul, D., Ayrik, C., et al. Chilaiditi sign: why are clinical findings more important in ED?. Am J Emerg Med. 2015;33:733.e1-733.e2.
2. Ho, M.P., Cheung, W.K., Tsai, K.C., et al. Chilaiditi syndrome mimicking subdiaphragmatic free air in an elderly adult. J Am Geriatr Soc. 2014;62:2019-21.
3. Kang, D., Pan, A.S., Lopez, M.A., et al. Acute abdominal pain secondary to Chilaiditi syndrome. Case Rep Surg. 2013;2013:756590.
Answer to “What’s your diagnosis?” Chilaiditi syndrome
Abdominal CT images display the Chilaiditi sign, which is the radiographic term used to describe interposition of the colon, usually at the hepatic flexure, with the liver and right diaphragm.1 This is considered an incidental radiographic finding and is generally asymptomatic; however, when one develops clinical symptoms such as abdominal pain, bloating or distension, anorexia, constipation, or nausea it is called Chilaiditi syndrome.
First described by Greek radiologist Demetrius Chilaiditi in 1910, Chilaiditi syndrome is a rare occurrence with an incidence rate of 0.25%-0.28% in the general population.2 The etiology of Chilaiditi syndrome is felt to be congenital or acquired with predisposing congenital abnormalities such as absent suspensory or falciform ligaments, redundant colon, malposition of the colon, dolichocolon, and paralysis of the right diaphragm. Other risk factors for development of Chilaiditi syndrome include chronic constipation, cirrhosis, ascites, and obesity. Men are times times as likely as women to develop Chilaiditi syndrome and it is more common in the elderly, occurring in 1% of the elderly population.3 Chilaiditi sign is diagnosed with radiographic imaging meeting the following criteria: the right hemidiaphragm must be elevated above the liver by the intestine, the bowel must be distended by air to illustrate pseudopneumoperitoneum, and the superior margin of the liver must be depressed below the level of the left hemidiaphragm.1
Chilaiditi syndrome is managed conservatively with close observation. Recurrent symptoms can be treated with colopexy. This syndrome has been known to cause severe complications including volvulus of the cecum, splenic flexure, or transverse colon, cecal perforation, and subdiaphragmatic perforated appendicitis, which all require surgical intervention.3 It is important to recognize Chilaiditi syndrome on presentation to prevent unnecessary diagnostic studies and unwarranted surgical intervention.
References
1. Uygungul, E., Uygungul, D., Ayrik, C., et al. Chilaiditi sign: why are clinical findings more important in ED?. Am J Emerg Med. 2015;33:733.e1-733.e2.
2. Ho, M.P., Cheung, W.K., Tsai, K.C., et al. Chilaiditi syndrome mimicking subdiaphragmatic free air in an elderly adult. J Am Geriatr Soc. 2014;62:2019-21.
3. Kang, D., Pan, A.S., Lopez, M.A., et al. Acute abdominal pain secondary to Chilaiditi syndrome. Case Rep Surg. 2013;2013:756590.
Answer to “What’s your diagnosis?” Chilaiditi syndrome
Abdominal CT images display the Chilaiditi sign, which is the radiographic term used to describe interposition of the colon, usually at the hepatic flexure, with the liver and right diaphragm.1 This is considered an incidental radiographic finding and is generally asymptomatic; however, when one develops clinical symptoms such as abdominal pain, bloating or distension, anorexia, constipation, or nausea it is called Chilaiditi syndrome.
First described by Greek radiologist Demetrius Chilaiditi in 1910, Chilaiditi syndrome is a rare occurrence with an incidence rate of 0.25%-0.28% in the general population.2 The etiology of Chilaiditi syndrome is felt to be congenital or acquired with predisposing congenital abnormalities such as absent suspensory or falciform ligaments, redundant colon, malposition of the colon, dolichocolon, and paralysis of the right diaphragm. Other risk factors for development of Chilaiditi syndrome include chronic constipation, cirrhosis, ascites, and obesity. Men are times times as likely as women to develop Chilaiditi syndrome and it is more common in the elderly, occurring in 1% of the elderly population.3 Chilaiditi sign is diagnosed with radiographic imaging meeting the following criteria: the right hemidiaphragm must be elevated above the liver by the intestine, the bowel must be distended by air to illustrate pseudopneumoperitoneum, and the superior margin of the liver must be depressed below the level of the left hemidiaphragm.1
Chilaiditi syndrome is managed conservatively with close observation. Recurrent symptoms can be treated with colopexy. This syndrome has been known to cause severe complications including volvulus of the cecum, splenic flexure, or transverse colon, cecal perforation, and subdiaphragmatic perforated appendicitis, which all require surgical intervention.3 It is important to recognize Chilaiditi syndrome on presentation to prevent unnecessary diagnostic studies and unwarranted surgical intervention.
References
1. Uygungul, E., Uygungul, D., Ayrik, C., et al. Chilaiditi sign: why are clinical findings more important in ED?. Am J Emerg Med. 2015;33:733.e1-733.e2.
2. Ho, M.P., Cheung, W.K., Tsai, K.C., et al. Chilaiditi syndrome mimicking subdiaphragmatic free air in an elderly adult. J Am Geriatr Soc. 2014;62:2019-21.
3. Kang, D., Pan, A.S., Lopez, M.A., et al. Acute abdominal pain secondary to Chilaiditi syndrome. Case Rep Surg. 2013;2013:756590.
By Jordan Orr, MD, and Charles O. Elson III, MD. Published previously in Gastroenterology (2016;151[2]:241-2).
A 67-year-old man presented to the emergency department with complaints of subacute, right-sided flank pain with migratory pain to his right lower quadrant and suprapubic area of increasing intensity for 1 week. He described his pain as cramping in nature and of fluctuating intensity, acutely worse on the day of presentation. However, within 15 minutes of waiting in the emergency department his pain subsided completely. He further denied any associated nausea, vomiting, diarrhea, melena, hematochezia, dysuria, or hematuria. Vital signs and abdominal physical examination were normal. Further, laboratory testing was unremarkable including a normal urinalysis. A bedside ultrasound was negative for gallbladder pathology or nephrolithiasis; however, it revealed an abnormal appearing liver. As further diagnostic work up, an abdominopelvic computed tomography scan revealed the following images (Figures A, B). The patient was discharged from the emergency department with scheduled follow-up in the gastroenterology clinic.
What is your diagnosis and treatment?
Opinions clash over private equity’s effect on dermatology
SAN DIEGO – Although practices that has been snowballing for a little under a decade is often bemoaned by dermatologists, at least some physicians in the field may see it as a positive development.
“I think private equity investment is good for dermatology,” Clifford Perlis, MD, said at the annual meeting of the American Academy of Dermatology. “Dermatologists should be thrilled that private equity is here.” Investment by private equity companies into dermatology practices “adds value to practices, creates more practice options, enhances advocacy, and better manages the complexity” of practices, claimed Dr. Perlis, a dermatologist and Mohs surgeon who practices in King of Prussia, Pa. The debate on this topic was presented during a forum on dermatoethics at the meeting, structured as a pro and con conversation. The organizers, including Dr. Perlis and Jane Grant-Kels, MD., chose the topics and assigned positions to each presenter, which do not necessarily represent their personal views.*
“The challenges to solo practice have nothing to do with private equity investment. It’s narrower insurance networks” that are squeezing out solo practices. He also expressed skepticism that private equity creates a barrier that interferes with the physician-patient relationship.
“Insurers and administrators already do that,” Dr. Perlis said in an interview. It’s “misguided” to place the blame on the financing. Rejection of private equity investment “clings to an outdated image of how medicine is practiced” that had already been disappearing for several decades before entry of private equity into dermatology began, he noted.
But other dermatologists have voiced concern about the changes brought by private equity investment.
“I’m frightened for the future of dermatology,” Jane M. Grant-Kels, MD, said at the meeting. “It shifts control [of patient care] away from dermatologists and into the hands of business and investors who are only interested in profit and not in quality of care,” she added.
“Have we learned nothing from dermatopathology, which has been ruined” by private equity, she asked. “The only ones who benefit are those making the private equity investments.” She cited similar, recently published views from other dermatologists, such as a recently published viewpoint article written by Jack S. Resneck Jr., MD, professor of dermatology, University of California, San Francisco (JAMA Dermatol. 2018 Jan 1;154[1]:13-4).
Dr. Perlis and Dr. Grant-Kels had no disclosures. They spoke during a session on dermatoethics at the AAD annual meeting. In an interview, Dr. Perlis said that his own personal views on this topic are far more nuanced.*
*This article was updated on April 4, 2018.
SAN DIEGO – Although practices that has been snowballing for a little under a decade is often bemoaned by dermatologists, at least some physicians in the field may see it as a positive development.
“I think private equity investment is good for dermatology,” Clifford Perlis, MD, said at the annual meeting of the American Academy of Dermatology. “Dermatologists should be thrilled that private equity is here.” Investment by private equity companies into dermatology practices “adds value to practices, creates more practice options, enhances advocacy, and better manages the complexity” of practices, claimed Dr. Perlis, a dermatologist and Mohs surgeon who practices in King of Prussia, Pa. The debate on this topic was presented during a forum on dermatoethics at the meeting, structured as a pro and con conversation. The organizers, including Dr. Perlis and Jane Grant-Kels, MD., chose the topics and assigned positions to each presenter, which do not necessarily represent their personal views.*
“The challenges to solo practice have nothing to do with private equity investment. It’s narrower insurance networks” that are squeezing out solo practices. He also expressed skepticism that private equity creates a barrier that interferes with the physician-patient relationship.
“Insurers and administrators already do that,” Dr. Perlis said in an interview. It’s “misguided” to place the blame on the financing. Rejection of private equity investment “clings to an outdated image of how medicine is practiced” that had already been disappearing for several decades before entry of private equity into dermatology began, he noted.
But other dermatologists have voiced concern about the changes brought by private equity investment.
“I’m frightened for the future of dermatology,” Jane M. Grant-Kels, MD, said at the meeting. “It shifts control [of patient care] away from dermatologists and into the hands of business and investors who are only interested in profit and not in quality of care,” she added.
“Have we learned nothing from dermatopathology, which has been ruined” by private equity, she asked. “The only ones who benefit are those making the private equity investments.” She cited similar, recently published views from other dermatologists, such as a recently published viewpoint article written by Jack S. Resneck Jr., MD, professor of dermatology, University of California, San Francisco (JAMA Dermatol. 2018 Jan 1;154[1]:13-4).
Dr. Perlis and Dr. Grant-Kels had no disclosures. They spoke during a session on dermatoethics at the AAD annual meeting. In an interview, Dr. Perlis said that his own personal views on this topic are far more nuanced.*
*This article was updated on April 4, 2018.
SAN DIEGO – Although practices that has been snowballing for a little under a decade is often bemoaned by dermatologists, at least some physicians in the field may see it as a positive development.
“I think private equity investment is good for dermatology,” Clifford Perlis, MD, said at the annual meeting of the American Academy of Dermatology. “Dermatologists should be thrilled that private equity is here.” Investment by private equity companies into dermatology practices “adds value to practices, creates more practice options, enhances advocacy, and better manages the complexity” of practices, claimed Dr. Perlis, a dermatologist and Mohs surgeon who practices in King of Prussia, Pa. The debate on this topic was presented during a forum on dermatoethics at the meeting, structured as a pro and con conversation. The organizers, including Dr. Perlis and Jane Grant-Kels, MD., chose the topics and assigned positions to each presenter, which do not necessarily represent their personal views.*
“The challenges to solo practice have nothing to do with private equity investment. It’s narrower insurance networks” that are squeezing out solo practices. He also expressed skepticism that private equity creates a barrier that interferes with the physician-patient relationship.
“Insurers and administrators already do that,” Dr. Perlis said in an interview. It’s “misguided” to place the blame on the financing. Rejection of private equity investment “clings to an outdated image of how medicine is practiced” that had already been disappearing for several decades before entry of private equity into dermatology began, he noted.
But other dermatologists have voiced concern about the changes brought by private equity investment.
“I’m frightened for the future of dermatology,” Jane M. Grant-Kels, MD, said at the meeting. “It shifts control [of patient care] away from dermatologists and into the hands of business and investors who are only interested in profit and not in quality of care,” she added.
“Have we learned nothing from dermatopathology, which has been ruined” by private equity, she asked. “The only ones who benefit are those making the private equity investments.” She cited similar, recently published views from other dermatologists, such as a recently published viewpoint article written by Jack S. Resneck Jr., MD, professor of dermatology, University of California, San Francisco (JAMA Dermatol. 2018 Jan 1;154[1]:13-4).
Dr. Perlis and Dr. Grant-Kels had no disclosures. They spoke during a session on dermatoethics at the AAD annual meeting. In an interview, Dr. Perlis said that his own personal views on this topic are far more nuanced.*
*This article was updated on April 4, 2018.
EXPERT ANALYSIS FROM AAD 18
HDAC inhibition may boost immune therapy efficacy in breast cancer
ORLANDO – The novel combination of entinostat and nivolumab with or without ipilimumab showed encouraging safety, tolerability, and antitumor activity in early results from an ongoing phase 1 trial of patients with advanced breast cancer.
Of 30 patients who were enrolled and treated in the dose-escalation phase of the study as of Feb. 24, 2018, 20 had evaluable responses, and of those, 3 had a partial response for an overall response rate of 15%. An additional 12 had stable disease, and 5 had disease progression, Roisin M. Connolly, MD, reported in a poster at the annual conference of the National Comprehensive Cancer Network.
Responses were seen in all 3 DL1 patients, 12 of 14 DL2 patients, 3 of 4 DL3 patients, and 2 of 9 (with 4 pending first restaging) DL4 patients. Dose-limiting toxicities included one case of pneumonitis at DL2 and an allergic reaction in one DL4 patient, said Dr. Connolly of Johns Hopkins University, Baltimore.
The most common treatment-associated adverse events occurring in 6 or more patients included anemia, fatigue, neutropenia, nausea, and rash, with each occurring in 12 to 22 patients, including grade 3 anemia in 7 patients, grade 3 fatigue in 4 patients, and grade 3 neutropenia in 5 patients. Grade 4 adverse events included lymphopenia in one patient and elevated lipase in one patient, she said.
Possible immune-related adverse events included hypothyroidism in 2 DL2 patients and 3 DL3 patients, hyperthyroidism in 1 DL3 patient, colitis in 1 DL2 and 1 DL3 patient, pneumonitis in 4 DL2 patients, rash in 10 DL2-DL4 patients, and meningoencephalitis and myasthenia gravis in 1 DL3 patient.
Study participants were adults with a mean age of 60 years with metastatic or unresectable solid tumors for which standard treatments did not exist or were no longer effective, or for which treatment with anti–programmed cell death ligand1/cytotoxic T-lymphocyte antigen 4 treatment was appropriate. All had good performance status and adequate organ and pulmonary function, less than 30% liver involvement, and any brain metastases were stable. Those with active autoimmune disease or a history of autoimmune disease that might recur were excluded, as were patients treated within 14 days of enrollment.
“The rationale for the study was based on preclinical work suggesting that epigenetic modifiers might be able to enhance the efficacy of immune therapies, and this would be particularly important for ‘colder’ tumor types like breast cancer that might not have the same sort of responses that we see in other tumor types,” Dr. Connolly explained in an interview. “The lab work suggested, for example, that the [histone deacetylase] inhibitor entinostat might affect myeloid-derived suppressor and regulatory T cells that might prevent cytotoxic T cells from fighting the cancer.”
There may be other mechanisms for this activity as well, she noted.
The run-in period with entinostat alone allowed collection of pre- and posttreatment biopsies to examine the effects on the tissues, such as whether treatment affects T cells, myeloid-derived suppressor cells, or their pathways, she said.
“We’re seeing [the] same types of toxicities seen with combination immune-oncology strategies, and we’re seeing some tumor responses that are of interest. Now we will delve into the tissue biopsies and blood samples we’ve collected to explore the mechanisms in more detail. In the near future we will open our breast cancer expansion cohort to look in more detail at what these drugs might be doing in breast cancer,” she added.
Specifically, she and her colleagues are evaluating the effects of treatment on immune-related biomarkers, measuring tumor-specific mutations and mutant neoantigens recognized by patient T cells in tumor biopsies, evaluating changes in the frequency of T cells recognizing tumor-specific mutant neoantigens in peripheral blood lymphocytes pre- and posttherapy, and looking at epigenetic changes pre- and posttherapy.
These preliminary findings suggest that the combination of entinostat and nivolumab with or without ipilimumab is safe and tolerable, with expected rates of immune-related adverse events, Dr. Connolly said, noting that the recommended phase 2 dose to be used in the dose expansion phase of the study has yet to be determined.
The findings, should they be confirmed as the trial progresses, could have important implications because immune checkpoint inhibitors, which work best in patients with immunogenic cancers that naturally attract T-cell infiltration into their tumor microenvironment, have limited single-agent activity in tumors, such as breast cancer, that are not believed to be immunogenic, she reported. Such cancers have thus far had only modest responses to single-agent immune checkpoint inhibition in advanced triple-negative and HER2+ breast cancer, with overall response rates of 5%-20%.
However, women who do respond to immune checkpoint inhibition tend to have durable and sustainable responses, she said, explaining that suboptimal immune responsiveness is likely a result of a lack of tumor antigen expression and/or recognition, as well as multiple suppressive signals in the tumor microenvironment.
Should the novel strategy tested in this study for converting breast cancers into immune responsive tumors facilitate improved response to immune checkpoint agents, it has the potential to significantly extend survival in breast cancer patients, she concluded.
This study was funded by grants from the National Institutes of Health, Bloomberg Kimmel Institute for Immunotherapy, NCCN, and the Mary Kay Foundation, as well as a V Foundation award. Dr. Connolly reported having no disclosures
SOURCE: Connolly RM et al. NCCN, Poster 3.
ORLANDO – The novel combination of entinostat and nivolumab with or without ipilimumab showed encouraging safety, tolerability, and antitumor activity in early results from an ongoing phase 1 trial of patients with advanced breast cancer.
Of 30 patients who were enrolled and treated in the dose-escalation phase of the study as of Feb. 24, 2018, 20 had evaluable responses, and of those, 3 had a partial response for an overall response rate of 15%. An additional 12 had stable disease, and 5 had disease progression, Roisin M. Connolly, MD, reported in a poster at the annual conference of the National Comprehensive Cancer Network.
Responses were seen in all 3 DL1 patients, 12 of 14 DL2 patients, 3 of 4 DL3 patients, and 2 of 9 (with 4 pending first restaging) DL4 patients. Dose-limiting toxicities included one case of pneumonitis at DL2 and an allergic reaction in one DL4 patient, said Dr. Connolly of Johns Hopkins University, Baltimore.
The most common treatment-associated adverse events occurring in 6 or more patients included anemia, fatigue, neutropenia, nausea, and rash, with each occurring in 12 to 22 patients, including grade 3 anemia in 7 patients, grade 3 fatigue in 4 patients, and grade 3 neutropenia in 5 patients. Grade 4 adverse events included lymphopenia in one patient and elevated lipase in one patient, she said.
Possible immune-related adverse events included hypothyroidism in 2 DL2 patients and 3 DL3 patients, hyperthyroidism in 1 DL3 patient, colitis in 1 DL2 and 1 DL3 patient, pneumonitis in 4 DL2 patients, rash in 10 DL2-DL4 patients, and meningoencephalitis and myasthenia gravis in 1 DL3 patient.
Study participants were adults with a mean age of 60 years with metastatic or unresectable solid tumors for which standard treatments did not exist or were no longer effective, or for which treatment with anti–programmed cell death ligand1/cytotoxic T-lymphocyte antigen 4 treatment was appropriate. All had good performance status and adequate organ and pulmonary function, less than 30% liver involvement, and any brain metastases were stable. Those with active autoimmune disease or a history of autoimmune disease that might recur were excluded, as were patients treated within 14 days of enrollment.
“The rationale for the study was based on preclinical work suggesting that epigenetic modifiers might be able to enhance the efficacy of immune therapies, and this would be particularly important for ‘colder’ tumor types like breast cancer that might not have the same sort of responses that we see in other tumor types,” Dr. Connolly explained in an interview. “The lab work suggested, for example, that the [histone deacetylase] inhibitor entinostat might affect myeloid-derived suppressor and regulatory T cells that might prevent cytotoxic T cells from fighting the cancer.”
There may be other mechanisms for this activity as well, she noted.
The run-in period with entinostat alone allowed collection of pre- and posttreatment biopsies to examine the effects on the tissues, such as whether treatment affects T cells, myeloid-derived suppressor cells, or their pathways, she said.
“We’re seeing [the] same types of toxicities seen with combination immune-oncology strategies, and we’re seeing some tumor responses that are of interest. Now we will delve into the tissue biopsies and blood samples we’ve collected to explore the mechanisms in more detail. In the near future we will open our breast cancer expansion cohort to look in more detail at what these drugs might be doing in breast cancer,” she added.
Specifically, she and her colleagues are evaluating the effects of treatment on immune-related biomarkers, measuring tumor-specific mutations and mutant neoantigens recognized by patient T cells in tumor biopsies, evaluating changes in the frequency of T cells recognizing tumor-specific mutant neoantigens in peripheral blood lymphocytes pre- and posttherapy, and looking at epigenetic changes pre- and posttherapy.
These preliminary findings suggest that the combination of entinostat and nivolumab with or without ipilimumab is safe and tolerable, with expected rates of immune-related adverse events, Dr. Connolly said, noting that the recommended phase 2 dose to be used in the dose expansion phase of the study has yet to be determined.
The findings, should they be confirmed as the trial progresses, could have important implications because immune checkpoint inhibitors, which work best in patients with immunogenic cancers that naturally attract T-cell infiltration into their tumor microenvironment, have limited single-agent activity in tumors, such as breast cancer, that are not believed to be immunogenic, she reported. Such cancers have thus far had only modest responses to single-agent immune checkpoint inhibition in advanced triple-negative and HER2+ breast cancer, with overall response rates of 5%-20%.
However, women who do respond to immune checkpoint inhibition tend to have durable and sustainable responses, she said, explaining that suboptimal immune responsiveness is likely a result of a lack of tumor antigen expression and/or recognition, as well as multiple suppressive signals in the tumor microenvironment.
Should the novel strategy tested in this study for converting breast cancers into immune responsive tumors facilitate improved response to immune checkpoint agents, it has the potential to significantly extend survival in breast cancer patients, she concluded.
This study was funded by grants from the National Institutes of Health, Bloomberg Kimmel Institute for Immunotherapy, NCCN, and the Mary Kay Foundation, as well as a V Foundation award. Dr. Connolly reported having no disclosures
SOURCE: Connolly RM et al. NCCN, Poster 3.
ORLANDO – The novel combination of entinostat and nivolumab with or without ipilimumab showed encouraging safety, tolerability, and antitumor activity in early results from an ongoing phase 1 trial of patients with advanced breast cancer.
Of 30 patients who were enrolled and treated in the dose-escalation phase of the study as of Feb. 24, 2018, 20 had evaluable responses, and of those, 3 had a partial response for an overall response rate of 15%. An additional 12 had stable disease, and 5 had disease progression, Roisin M. Connolly, MD, reported in a poster at the annual conference of the National Comprehensive Cancer Network.
Responses were seen in all 3 DL1 patients, 12 of 14 DL2 patients, 3 of 4 DL3 patients, and 2 of 9 (with 4 pending first restaging) DL4 patients. Dose-limiting toxicities included one case of pneumonitis at DL2 and an allergic reaction in one DL4 patient, said Dr. Connolly of Johns Hopkins University, Baltimore.
The most common treatment-associated adverse events occurring in 6 or more patients included anemia, fatigue, neutropenia, nausea, and rash, with each occurring in 12 to 22 patients, including grade 3 anemia in 7 patients, grade 3 fatigue in 4 patients, and grade 3 neutropenia in 5 patients. Grade 4 adverse events included lymphopenia in one patient and elevated lipase in one patient, she said.
Possible immune-related adverse events included hypothyroidism in 2 DL2 patients and 3 DL3 patients, hyperthyroidism in 1 DL3 patient, colitis in 1 DL2 and 1 DL3 patient, pneumonitis in 4 DL2 patients, rash in 10 DL2-DL4 patients, and meningoencephalitis and myasthenia gravis in 1 DL3 patient.
Study participants were adults with a mean age of 60 years with metastatic or unresectable solid tumors for which standard treatments did not exist or were no longer effective, or for which treatment with anti–programmed cell death ligand1/cytotoxic T-lymphocyte antigen 4 treatment was appropriate. All had good performance status and adequate organ and pulmonary function, less than 30% liver involvement, and any brain metastases were stable. Those with active autoimmune disease or a history of autoimmune disease that might recur were excluded, as were patients treated within 14 days of enrollment.
“The rationale for the study was based on preclinical work suggesting that epigenetic modifiers might be able to enhance the efficacy of immune therapies, and this would be particularly important for ‘colder’ tumor types like breast cancer that might not have the same sort of responses that we see in other tumor types,” Dr. Connolly explained in an interview. “The lab work suggested, for example, that the [histone deacetylase] inhibitor entinostat might affect myeloid-derived suppressor and regulatory T cells that might prevent cytotoxic T cells from fighting the cancer.”
There may be other mechanisms for this activity as well, she noted.
The run-in period with entinostat alone allowed collection of pre- and posttreatment biopsies to examine the effects on the tissues, such as whether treatment affects T cells, myeloid-derived suppressor cells, or their pathways, she said.
“We’re seeing [the] same types of toxicities seen with combination immune-oncology strategies, and we’re seeing some tumor responses that are of interest. Now we will delve into the tissue biopsies and blood samples we’ve collected to explore the mechanisms in more detail. In the near future we will open our breast cancer expansion cohort to look in more detail at what these drugs might be doing in breast cancer,” she added.
Specifically, she and her colleagues are evaluating the effects of treatment on immune-related biomarkers, measuring tumor-specific mutations and mutant neoantigens recognized by patient T cells in tumor biopsies, evaluating changes in the frequency of T cells recognizing tumor-specific mutant neoantigens in peripheral blood lymphocytes pre- and posttherapy, and looking at epigenetic changes pre- and posttherapy.
These preliminary findings suggest that the combination of entinostat and nivolumab with or without ipilimumab is safe and tolerable, with expected rates of immune-related adverse events, Dr. Connolly said, noting that the recommended phase 2 dose to be used in the dose expansion phase of the study has yet to be determined.
The findings, should they be confirmed as the trial progresses, could have important implications because immune checkpoint inhibitors, which work best in patients with immunogenic cancers that naturally attract T-cell infiltration into their tumor microenvironment, have limited single-agent activity in tumors, such as breast cancer, that are not believed to be immunogenic, she reported. Such cancers have thus far had only modest responses to single-agent immune checkpoint inhibition in advanced triple-negative and HER2+ breast cancer, with overall response rates of 5%-20%.
However, women who do respond to immune checkpoint inhibition tend to have durable and sustainable responses, she said, explaining that suboptimal immune responsiveness is likely a result of a lack of tumor antigen expression and/or recognition, as well as multiple suppressive signals in the tumor microenvironment.
Should the novel strategy tested in this study for converting breast cancers into immune responsive tumors facilitate improved response to immune checkpoint agents, it has the potential to significantly extend survival in breast cancer patients, she concluded.
This study was funded by grants from the National Institutes of Health, Bloomberg Kimmel Institute for Immunotherapy, NCCN, and the Mary Kay Foundation, as well as a V Foundation award. Dr. Connolly reported having no disclosures
SOURCE: Connolly RM et al. NCCN, Poster 3.
REPORTING FROM THE NCCN ANNUAL CONFERENCE
Key clinical point:
Major finding: Three patients had a partial response, 12 had stable disease, 5 progressed.
Study details: A phase 1 dose-expansion study involving 30 patients.
Disclosures: This study was funded by grants from the National Institutes of Health, Bloomberg Kimmel Institute for Immunotherapy, NCCN, and the Mary Kay Foundation, and by a V Foundation award. Dr. Connolly reported having no disclosures.
Source: Connolly RM et al. NCCN, Poster 3.
Sling revisions: pain as indication linked with SUI recurrence
ORLANDO – Pain as an indication for midurethral sling revision is associated with an elevated risk of postoperative stress urinary incontinence recurrence, according to a review of 129 cases.
At a mean follow-up of 21 months, the overall rate of recurrent stress urinary incontinence (SUI) among study subjects was 39.5%, which is similar to what has been previously reported in the literature. However, women who underwent revision for the indication of pain, including dyspareunia, pelvic pain, or muscle spasms, had an SUI recurrence rate of 70%, Meagan S. Cramer, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.
Women older than 55 years at the time of revision were significantly less likely to recur (adjusted odds ratio, 0.34 vs. younger women), and those whose original slings were placed less than 1 year prior to revision had a significantly lower rate of SUI recurrence, compared with those whose slings were placed more than 1 year prior (23.1% vs. 46.7%), she noted.
“There was no difference in BMI [body mass index], race, or baseline comorbidities between the recurrence vs. no recurrence group. There was also no difference in estrogen use preoperatively, concurrent replacement with another sling, preoperative [pelvic organ prolapse quantification] exam, length of sling excised, or the original type of sling placed between the recurrence versus non recurrence groups,” she said. “On multivariable regression analysis controlling for age, BMI, race, tobacco use, time since original sling, erosion on exam, technique used for revision, and presenting indication, pain as an indication of revision was still associated with an increased risk for recurrent incontinence, with an adjusted odds ratio of 9.08.”
Study subjects were women aged 18 years and older who underwent mesh sling revision from January 2009 to July 2016 at a single center. Women were excluded if they underwent revision or excision of vaginal mesh, or if they underwent sling adjustment for persistent incontinence if the incontinence had never resolved after the original sling placement. Those without postoperative follow-up were also excluded.
“Approximately 2%-4% of women who undergo midurethral sling surgery for stress incontinence will later require revision or excision of the sling due to erosion, pain, and/or voiding dysfunction. Based on current literature, up to 56% of these women can experience postoperative recurrence of stress incontinence following their revision,” Dr. Cramer said, noting that there is no consensus on which women will require future surgeries for stress incontinence after revision.
In the current study, women with pain were significantly more likely to undergo a complete excision of their sling (45.0% vs. 17.9% with other indications).
“We also discovered that of all women who underwent complete excision of a prior sling, those with pain had a higher rate of recurrent SUI, compared with those without pain [66.7% vs. 31.6%], but the difference was not statistically significant,” Dr. Cramer said in an interview.
She noted, however, that partial sling excision has been shown in at least one prior study “to provide just as much benefit as complete sling excision for patients with pain without leading to an increased risk of SUI.”
Though limited by the retrospective study design, the current findings suggest that pain as an indication for sling revision is associated with a higher risk of postoperative recurrent SUI, regardless of the type of revision, she said.
“Future prospective studies investigating the relationship between the indication for revision and postoperative stress incontinence would help to further define the roles of pain in this process,” she said, adding that in the meantime, given the prior findings regarding the benefits of partial sling excision, it may be reasonable to advise patients with pain that undergoing a partial sling excision could reduce the risk of recurrent SUI.
Dr. Cramer reported having no disclosures.
SOURCE: Cramer MS et al. SGS 2018, Oral Presentation 04.
ORLANDO – Pain as an indication for midurethral sling revision is associated with an elevated risk of postoperative stress urinary incontinence recurrence, according to a review of 129 cases.
At a mean follow-up of 21 months, the overall rate of recurrent stress urinary incontinence (SUI) among study subjects was 39.5%, which is similar to what has been previously reported in the literature. However, women who underwent revision for the indication of pain, including dyspareunia, pelvic pain, or muscle spasms, had an SUI recurrence rate of 70%, Meagan S. Cramer, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.
Women older than 55 years at the time of revision were significantly less likely to recur (adjusted odds ratio, 0.34 vs. younger women), and those whose original slings were placed less than 1 year prior to revision had a significantly lower rate of SUI recurrence, compared with those whose slings were placed more than 1 year prior (23.1% vs. 46.7%), she noted.
“There was no difference in BMI [body mass index], race, or baseline comorbidities between the recurrence vs. no recurrence group. There was also no difference in estrogen use preoperatively, concurrent replacement with another sling, preoperative [pelvic organ prolapse quantification] exam, length of sling excised, or the original type of sling placed between the recurrence versus non recurrence groups,” she said. “On multivariable regression analysis controlling for age, BMI, race, tobacco use, time since original sling, erosion on exam, technique used for revision, and presenting indication, pain as an indication of revision was still associated with an increased risk for recurrent incontinence, with an adjusted odds ratio of 9.08.”
Study subjects were women aged 18 years and older who underwent mesh sling revision from January 2009 to July 2016 at a single center. Women were excluded if they underwent revision or excision of vaginal mesh, or if they underwent sling adjustment for persistent incontinence if the incontinence had never resolved after the original sling placement. Those without postoperative follow-up were also excluded.
“Approximately 2%-4% of women who undergo midurethral sling surgery for stress incontinence will later require revision or excision of the sling due to erosion, pain, and/or voiding dysfunction. Based on current literature, up to 56% of these women can experience postoperative recurrence of stress incontinence following their revision,” Dr. Cramer said, noting that there is no consensus on which women will require future surgeries for stress incontinence after revision.
In the current study, women with pain were significantly more likely to undergo a complete excision of their sling (45.0% vs. 17.9% with other indications).
“We also discovered that of all women who underwent complete excision of a prior sling, those with pain had a higher rate of recurrent SUI, compared with those without pain [66.7% vs. 31.6%], but the difference was not statistically significant,” Dr. Cramer said in an interview.
She noted, however, that partial sling excision has been shown in at least one prior study “to provide just as much benefit as complete sling excision for patients with pain without leading to an increased risk of SUI.”
Though limited by the retrospective study design, the current findings suggest that pain as an indication for sling revision is associated with a higher risk of postoperative recurrent SUI, regardless of the type of revision, she said.
“Future prospective studies investigating the relationship between the indication for revision and postoperative stress incontinence would help to further define the roles of pain in this process,” she said, adding that in the meantime, given the prior findings regarding the benefits of partial sling excision, it may be reasonable to advise patients with pain that undergoing a partial sling excision could reduce the risk of recurrent SUI.
Dr. Cramer reported having no disclosures.
SOURCE: Cramer MS et al. SGS 2018, Oral Presentation 04.
ORLANDO – Pain as an indication for midurethral sling revision is associated with an elevated risk of postoperative stress urinary incontinence recurrence, according to a review of 129 cases.
At a mean follow-up of 21 months, the overall rate of recurrent stress urinary incontinence (SUI) among study subjects was 39.5%, which is similar to what has been previously reported in the literature. However, women who underwent revision for the indication of pain, including dyspareunia, pelvic pain, or muscle spasms, had an SUI recurrence rate of 70%, Meagan S. Cramer, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.
Women older than 55 years at the time of revision were significantly less likely to recur (adjusted odds ratio, 0.34 vs. younger women), and those whose original slings were placed less than 1 year prior to revision had a significantly lower rate of SUI recurrence, compared with those whose slings were placed more than 1 year prior (23.1% vs. 46.7%), she noted.
“There was no difference in BMI [body mass index], race, or baseline comorbidities between the recurrence vs. no recurrence group. There was also no difference in estrogen use preoperatively, concurrent replacement with another sling, preoperative [pelvic organ prolapse quantification] exam, length of sling excised, or the original type of sling placed between the recurrence versus non recurrence groups,” she said. “On multivariable regression analysis controlling for age, BMI, race, tobacco use, time since original sling, erosion on exam, technique used for revision, and presenting indication, pain as an indication of revision was still associated with an increased risk for recurrent incontinence, with an adjusted odds ratio of 9.08.”
Study subjects were women aged 18 years and older who underwent mesh sling revision from January 2009 to July 2016 at a single center. Women were excluded if they underwent revision or excision of vaginal mesh, or if they underwent sling adjustment for persistent incontinence if the incontinence had never resolved after the original sling placement. Those without postoperative follow-up were also excluded.
“Approximately 2%-4% of women who undergo midurethral sling surgery for stress incontinence will later require revision or excision of the sling due to erosion, pain, and/or voiding dysfunction. Based on current literature, up to 56% of these women can experience postoperative recurrence of stress incontinence following their revision,” Dr. Cramer said, noting that there is no consensus on which women will require future surgeries for stress incontinence after revision.
In the current study, women with pain were significantly more likely to undergo a complete excision of their sling (45.0% vs. 17.9% with other indications).
“We also discovered that of all women who underwent complete excision of a prior sling, those with pain had a higher rate of recurrent SUI, compared with those without pain [66.7% vs. 31.6%], but the difference was not statistically significant,” Dr. Cramer said in an interview.
She noted, however, that partial sling excision has been shown in at least one prior study “to provide just as much benefit as complete sling excision for patients with pain without leading to an increased risk of SUI.”
Though limited by the retrospective study design, the current findings suggest that pain as an indication for sling revision is associated with a higher risk of postoperative recurrent SUI, regardless of the type of revision, she said.
“Future prospective studies investigating the relationship between the indication for revision and postoperative stress incontinence would help to further define the roles of pain in this process,” she said, adding that in the meantime, given the prior findings regarding the benefits of partial sling excision, it may be reasonable to advise patients with pain that undergoing a partial sling excision could reduce the risk of recurrent SUI.
Dr. Cramer reported having no disclosures.
SOURCE: Cramer MS et al. SGS 2018, Oral Presentation 04.
REPORTING FROM SGS 2018
Key clinical point: Sling revisions for pain may increase the risk of postoperative stress urinary incontinence recurrence.
Major finding: The recurrent SUI rate after revision was 39.5% overall vs. 70% among those with pain as an indication.
Study details: A retrospective cohort study of 129 women.
Disclosures: Dr. Cramer reported having no disclosures.
Source: Cramer MS et al. SGS 2018, Oral Presentation 04.
Dr. T. Berry Brazelton was a pioneer of child-centered parenting
You may not realize it, but as you navigated through this morning’s hospital rounds and your busy office schedule, some of what you did and how you did it was the result of the pioneering work of Boston-based pediatrician T. Berry Brazelton, MD, who died March 13, 2018, at the age of 99.
You probably found the newborn you needed to examine in his mother’s hospital room. The 3-year-old in the croup tent was sharing his room with his father, who was sleeping on a cot at his crib side, and three out of the first four patients you saw in your office had been breastfed. These scenarios would have been unheard of 50 years ago. But Dr. Brazelton’s voice was the most widely heard, yet gentlest and persuasive in support of rooming-in and breastfeeding.
My fellow house officers and I had been accustomed to picking up infants to assess their tone. However, when Dr. Brazelton picked up a newborn, it was more like a conversation, an interview, and in a sense, it was a meeting of the minds.
It wasn’t that we had been rejecting the notion that a newborn could have a personality. It is just that we hadn’t been taught to look for it or to take it seriously. Dr. Brazelton taught us how to examine the person inside that little body and understand the importance of her temperament. By sharing what we learned from doing a Brazelton-style exam, we hoped to encourage the child’s parents to adopt more realistic expectations, and as a consequence, make parenting less mysterious and stressful.
When I first met Dr. Brazelton, he was in his mid-40s and just beginning on his trajectory toward national prominence. When we were assigned to take care of his hospitalized patients, it was obvious that his patient skills with sick children had taken a back seat to his interest in newborn temperament. He was more than willing to let us make the management decisions. In retrospect, that experience was a warning that I, like many other pediatricians, would face the similar challenge of maintaining my clinical skills in the face of a patient mix that was steadily acquiring a more behavioral and developmental flavor.
It is impossible to quantify the degree to which Dr. Brazelton’s ubiquity contributed to the popularity of a more child-centered parenting style. However, I think it would be unfair to blame him for the unfortunate phenomenon known as “helicopter parenting.”
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
You may not realize it, but as you navigated through this morning’s hospital rounds and your busy office schedule, some of what you did and how you did it was the result of the pioneering work of Boston-based pediatrician T. Berry Brazelton, MD, who died March 13, 2018, at the age of 99.
You probably found the newborn you needed to examine in his mother’s hospital room. The 3-year-old in the croup tent was sharing his room with his father, who was sleeping on a cot at his crib side, and three out of the first four patients you saw in your office had been breastfed. These scenarios would have been unheard of 50 years ago. But Dr. Brazelton’s voice was the most widely heard, yet gentlest and persuasive in support of rooming-in and breastfeeding.
My fellow house officers and I had been accustomed to picking up infants to assess their tone. However, when Dr. Brazelton picked up a newborn, it was more like a conversation, an interview, and in a sense, it was a meeting of the minds.
It wasn’t that we had been rejecting the notion that a newborn could have a personality. It is just that we hadn’t been taught to look for it or to take it seriously. Dr. Brazelton taught us how to examine the person inside that little body and understand the importance of her temperament. By sharing what we learned from doing a Brazelton-style exam, we hoped to encourage the child’s parents to adopt more realistic expectations, and as a consequence, make parenting less mysterious and stressful.
When I first met Dr. Brazelton, he was in his mid-40s and just beginning on his trajectory toward national prominence. When we were assigned to take care of his hospitalized patients, it was obvious that his patient skills with sick children had taken a back seat to his interest in newborn temperament. He was more than willing to let us make the management decisions. In retrospect, that experience was a warning that I, like many other pediatricians, would face the similar challenge of maintaining my clinical skills in the face of a patient mix that was steadily acquiring a more behavioral and developmental flavor.
It is impossible to quantify the degree to which Dr. Brazelton’s ubiquity contributed to the popularity of a more child-centered parenting style. However, I think it would be unfair to blame him for the unfortunate phenomenon known as “helicopter parenting.”
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
You may not realize it, but as you navigated through this morning’s hospital rounds and your busy office schedule, some of what you did and how you did it was the result of the pioneering work of Boston-based pediatrician T. Berry Brazelton, MD, who died March 13, 2018, at the age of 99.
You probably found the newborn you needed to examine in his mother’s hospital room. The 3-year-old in the croup tent was sharing his room with his father, who was sleeping on a cot at his crib side, and three out of the first four patients you saw in your office had been breastfed. These scenarios would have been unheard of 50 years ago. But Dr. Brazelton’s voice was the most widely heard, yet gentlest and persuasive in support of rooming-in and breastfeeding.
My fellow house officers and I had been accustomed to picking up infants to assess their tone. However, when Dr. Brazelton picked up a newborn, it was more like a conversation, an interview, and in a sense, it was a meeting of the minds.
It wasn’t that we had been rejecting the notion that a newborn could have a personality. It is just that we hadn’t been taught to look for it or to take it seriously. Dr. Brazelton taught us how to examine the person inside that little body and understand the importance of her temperament. By sharing what we learned from doing a Brazelton-style exam, we hoped to encourage the child’s parents to adopt more realistic expectations, and as a consequence, make parenting less mysterious and stressful.
When I first met Dr. Brazelton, he was in his mid-40s and just beginning on his trajectory toward national prominence. When we were assigned to take care of his hospitalized patients, it was obvious that his patient skills with sick children had taken a back seat to his interest in newborn temperament. He was more than willing to let us make the management decisions. In retrospect, that experience was a warning that I, like many other pediatricians, would face the similar challenge of maintaining my clinical skills in the face of a patient mix that was steadily acquiring a more behavioral and developmental flavor.
It is impossible to quantify the degree to which Dr. Brazelton’s ubiquity contributed to the popularity of a more child-centered parenting style. However, I think it would be unfair to blame him for the unfortunate phenomenon known as “helicopter parenting.”
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Femoral artery endarterectomy still ‘gold standard’
CHICAGO – Additional higher quality supporting evidence is needed before , Jeffrey J. Siracuse, MD, FACS, asserted at a symposium on vascular surgery sponsored by Northwestern University.
“Open surgery in the CFA [common femoral artery] is probably still the gold standard in most cases,” said Dr. Siracuse, a vascular surgeon at Boston University.
He was quick to note that others would disagree. Stenting and other endovascular interventions in the CFA are booming in popularity, particularly among cardiologists, interventional radiologists, and the patients to whom the clinicians present the option in a favorable light. But this enthusiasm is based almost entirely on small, single-center, retrospective studies conducted in patients with heterogeneous profiles. The one prospective randomized multicenter trial of stenting versus surgery for CFA stenosis published to date – the French TECCO study – has a number of key limitations, flaws, and unanswered questions, which endovascular proponents have overlooked in their enthusiasm to promote an “endo-first” approach in the CFA, according to Dr. Siracuse.
“Everyone’s pretty much jumping on the bandwagon now. I think endovascular therapy of the CFA is here to stay. You’re going to see more people doing it, and potentially doing it incorrectly,” he predicted.
“The biggest thing I worry about with stenting is covering or jailing out the deep femoral artery. On multiple occasions – including a case just 2 weeks ago – I’ve taken out stents placed in the CFA by others that developed in-stent hyperplasia to the extent that the entire stent goes down, the DFA is covered, and now all of a sudden you’ve lost all flow to the leg. That’s my biggest concern with stenting,” he said.
Dr. Siracuse has other reservations as well. The CFA has traditionally been considered a “no-stent zone” because of the unique biomechanical stresses the artery is subjected to as a result of torsion, flexion, and extension at the hip joint. These forces render the area particularly vulnerable to neointimal hyperplasia, acute thrombosis, and stent fracture.
In addition, he noted, CFA endarterectomy for atherosclerotic lesions is a mature, well-established operation with an excellent track record for safety and durability. Dr. Siracuse’s review of procedural safety in 1,513 patients in the American College of Surgeons National Surgical Quality Improvement Project database during 2007-2010 showed a 30-day mortality of 1.5% and a 7.9% rate of major or minor complications (Vasc Endovascular Surg. 2014 Jan;48[1]:27-33).
In contrast, his review of 1,014 patients who underwent nonemergent endovascular CFA interventions for CFA stenosis without acute limb ischemia in the Vascular Quality Initiative registry demonstrated a 1-year patency rate of 85.3%, significantly lower than historically observed patency rates for endarterectomy. The 30-day mortality rate of 1.6% associated with endovascular interventions was essentially the same as in his earlier analysis of endarterectomy in the ACS NSQIP database, and the average 1.5-day hospital length of stay was shorter than with open surgery. Of considerable concern, however, stent implantation, which was performed in 35% of the endovascular interventions, was an independent predictor of amputation or death, with an associated 195% increased risk (J Vasc Surg. 2017 Apr;[4]:1039-46).
The travails of TECCO
The 17-center French TECCO study randomized 117 patients with de novo CFA atherosclerotic lesions to treatment via self-expanding stents or open surgery. A total of 98 participants were Rutherford stage 3, making TECCO primarily a study of claudicants. The primary outcome – the 30-day combined rate of morbidity and mortality – occurred in 26% of the surgical patients, a significantly higher rate than the 12.5% in the stent population. After a median follow-up of 24 months, the rates of primary patency, target lesion and extremity revascularization, and sustained clinical improvement were similar in the two groups (JACC Cardiovasc Interv. 2017 Jul 10;10[13]:1344-54).
The TECCO findings were hailed by endovascular therapy partisans as a big win. However, closer examination tells a different story, according to Dr. Siracuse.
There was no 30-day mortality in this rather small study. All 16 morbidity events occurring in the open surgery group within 30 days were relatively minor: 10 cases of delayed wound healing, 4 cases of postoperative paresthesia requiring medication, and 2 cases of lymphorrhea lasting longer than 3 days. In contrast, the seven morbidity events in the stent group included a complication requiring urgent open surgical repair at the time of stenting, one stent fracture, and a major amputation.
“The investigators didn’t elaborate on that major amputation, but I thought it was a little alarming because you should not have a major amputation with CFA interventions for claudicants,” the vascular surgeon commented. “Really, do people care about a lymphatic leak or do they care about amputation? I think more needs to be fleshed out about what really happened in that case.”
He was also puzzled by the hospital lengths of stay: a mean of 3.2 days in the stent group and 6.3 days in the open surgery group. “I think those lengths of stay are astounding. Very high and unusual,” he observed.
Dr. Siracuse predicted that much-needed high-quality data comparing treatments of the CFA will be provided by the BEST-CLI trial (Best Endovascular versus Surgical Treatment for Critical Limb Ischemia), which has been updated to include both open and endovascular interventions.
He reported having no financial conflicts of interest regarding his presentation.
CHICAGO – Additional higher quality supporting evidence is needed before , Jeffrey J. Siracuse, MD, FACS, asserted at a symposium on vascular surgery sponsored by Northwestern University.
“Open surgery in the CFA [common femoral artery] is probably still the gold standard in most cases,” said Dr. Siracuse, a vascular surgeon at Boston University.
He was quick to note that others would disagree. Stenting and other endovascular interventions in the CFA are booming in popularity, particularly among cardiologists, interventional radiologists, and the patients to whom the clinicians present the option in a favorable light. But this enthusiasm is based almost entirely on small, single-center, retrospective studies conducted in patients with heterogeneous profiles. The one prospective randomized multicenter trial of stenting versus surgery for CFA stenosis published to date – the French TECCO study – has a number of key limitations, flaws, and unanswered questions, which endovascular proponents have overlooked in their enthusiasm to promote an “endo-first” approach in the CFA, according to Dr. Siracuse.
“Everyone’s pretty much jumping on the bandwagon now. I think endovascular therapy of the CFA is here to stay. You’re going to see more people doing it, and potentially doing it incorrectly,” he predicted.
“The biggest thing I worry about with stenting is covering or jailing out the deep femoral artery. On multiple occasions – including a case just 2 weeks ago – I’ve taken out stents placed in the CFA by others that developed in-stent hyperplasia to the extent that the entire stent goes down, the DFA is covered, and now all of a sudden you’ve lost all flow to the leg. That’s my biggest concern with stenting,” he said.
Dr. Siracuse has other reservations as well. The CFA has traditionally been considered a “no-stent zone” because of the unique biomechanical stresses the artery is subjected to as a result of torsion, flexion, and extension at the hip joint. These forces render the area particularly vulnerable to neointimal hyperplasia, acute thrombosis, and stent fracture.
In addition, he noted, CFA endarterectomy for atherosclerotic lesions is a mature, well-established operation with an excellent track record for safety and durability. Dr. Siracuse’s review of procedural safety in 1,513 patients in the American College of Surgeons National Surgical Quality Improvement Project database during 2007-2010 showed a 30-day mortality of 1.5% and a 7.9% rate of major or minor complications (Vasc Endovascular Surg. 2014 Jan;48[1]:27-33).
In contrast, his review of 1,014 patients who underwent nonemergent endovascular CFA interventions for CFA stenosis without acute limb ischemia in the Vascular Quality Initiative registry demonstrated a 1-year patency rate of 85.3%, significantly lower than historically observed patency rates for endarterectomy. The 30-day mortality rate of 1.6% associated with endovascular interventions was essentially the same as in his earlier analysis of endarterectomy in the ACS NSQIP database, and the average 1.5-day hospital length of stay was shorter than with open surgery. Of considerable concern, however, stent implantation, which was performed in 35% of the endovascular interventions, was an independent predictor of amputation or death, with an associated 195% increased risk (J Vasc Surg. 2017 Apr;[4]:1039-46).
The travails of TECCO
The 17-center French TECCO study randomized 117 patients with de novo CFA atherosclerotic lesions to treatment via self-expanding stents or open surgery. A total of 98 participants were Rutherford stage 3, making TECCO primarily a study of claudicants. The primary outcome – the 30-day combined rate of morbidity and mortality – occurred in 26% of the surgical patients, a significantly higher rate than the 12.5% in the stent population. After a median follow-up of 24 months, the rates of primary patency, target lesion and extremity revascularization, and sustained clinical improvement were similar in the two groups (JACC Cardiovasc Interv. 2017 Jul 10;10[13]:1344-54).
The TECCO findings were hailed by endovascular therapy partisans as a big win. However, closer examination tells a different story, according to Dr. Siracuse.
There was no 30-day mortality in this rather small study. All 16 morbidity events occurring in the open surgery group within 30 days were relatively minor: 10 cases of delayed wound healing, 4 cases of postoperative paresthesia requiring medication, and 2 cases of lymphorrhea lasting longer than 3 days. In contrast, the seven morbidity events in the stent group included a complication requiring urgent open surgical repair at the time of stenting, one stent fracture, and a major amputation.
“The investigators didn’t elaborate on that major amputation, but I thought it was a little alarming because you should not have a major amputation with CFA interventions for claudicants,” the vascular surgeon commented. “Really, do people care about a lymphatic leak or do they care about amputation? I think more needs to be fleshed out about what really happened in that case.”
He was also puzzled by the hospital lengths of stay: a mean of 3.2 days in the stent group and 6.3 days in the open surgery group. “I think those lengths of stay are astounding. Very high and unusual,” he observed.
Dr. Siracuse predicted that much-needed high-quality data comparing treatments of the CFA will be provided by the BEST-CLI trial (Best Endovascular versus Surgical Treatment for Critical Limb Ischemia), which has been updated to include both open and endovascular interventions.
He reported having no financial conflicts of interest regarding his presentation.
CHICAGO – Additional higher quality supporting evidence is needed before , Jeffrey J. Siracuse, MD, FACS, asserted at a symposium on vascular surgery sponsored by Northwestern University.
“Open surgery in the CFA [common femoral artery] is probably still the gold standard in most cases,” said Dr. Siracuse, a vascular surgeon at Boston University.
He was quick to note that others would disagree. Stenting and other endovascular interventions in the CFA are booming in popularity, particularly among cardiologists, interventional radiologists, and the patients to whom the clinicians present the option in a favorable light. But this enthusiasm is based almost entirely on small, single-center, retrospective studies conducted in patients with heterogeneous profiles. The one prospective randomized multicenter trial of stenting versus surgery for CFA stenosis published to date – the French TECCO study – has a number of key limitations, flaws, and unanswered questions, which endovascular proponents have overlooked in their enthusiasm to promote an “endo-first” approach in the CFA, according to Dr. Siracuse.
“Everyone’s pretty much jumping on the bandwagon now. I think endovascular therapy of the CFA is here to stay. You’re going to see more people doing it, and potentially doing it incorrectly,” he predicted.
“The biggest thing I worry about with stenting is covering or jailing out the deep femoral artery. On multiple occasions – including a case just 2 weeks ago – I’ve taken out stents placed in the CFA by others that developed in-stent hyperplasia to the extent that the entire stent goes down, the DFA is covered, and now all of a sudden you’ve lost all flow to the leg. That’s my biggest concern with stenting,” he said.
Dr. Siracuse has other reservations as well. The CFA has traditionally been considered a “no-stent zone” because of the unique biomechanical stresses the artery is subjected to as a result of torsion, flexion, and extension at the hip joint. These forces render the area particularly vulnerable to neointimal hyperplasia, acute thrombosis, and stent fracture.
In addition, he noted, CFA endarterectomy for atherosclerotic lesions is a mature, well-established operation with an excellent track record for safety and durability. Dr. Siracuse’s review of procedural safety in 1,513 patients in the American College of Surgeons National Surgical Quality Improvement Project database during 2007-2010 showed a 30-day mortality of 1.5% and a 7.9% rate of major or minor complications (Vasc Endovascular Surg. 2014 Jan;48[1]:27-33).
In contrast, his review of 1,014 patients who underwent nonemergent endovascular CFA interventions for CFA stenosis without acute limb ischemia in the Vascular Quality Initiative registry demonstrated a 1-year patency rate of 85.3%, significantly lower than historically observed patency rates for endarterectomy. The 30-day mortality rate of 1.6% associated with endovascular interventions was essentially the same as in his earlier analysis of endarterectomy in the ACS NSQIP database, and the average 1.5-day hospital length of stay was shorter than with open surgery. Of considerable concern, however, stent implantation, which was performed in 35% of the endovascular interventions, was an independent predictor of amputation or death, with an associated 195% increased risk (J Vasc Surg. 2017 Apr;[4]:1039-46).
The travails of TECCO
The 17-center French TECCO study randomized 117 patients with de novo CFA atherosclerotic lesions to treatment via self-expanding stents or open surgery. A total of 98 participants were Rutherford stage 3, making TECCO primarily a study of claudicants. The primary outcome – the 30-day combined rate of morbidity and mortality – occurred in 26% of the surgical patients, a significantly higher rate than the 12.5% in the stent population. After a median follow-up of 24 months, the rates of primary patency, target lesion and extremity revascularization, and sustained clinical improvement were similar in the two groups (JACC Cardiovasc Interv. 2017 Jul 10;10[13]:1344-54).
The TECCO findings were hailed by endovascular therapy partisans as a big win. However, closer examination tells a different story, according to Dr. Siracuse.
There was no 30-day mortality in this rather small study. All 16 morbidity events occurring in the open surgery group within 30 days were relatively minor: 10 cases of delayed wound healing, 4 cases of postoperative paresthesia requiring medication, and 2 cases of lymphorrhea lasting longer than 3 days. In contrast, the seven morbidity events in the stent group included a complication requiring urgent open surgical repair at the time of stenting, one stent fracture, and a major amputation.
“The investigators didn’t elaborate on that major amputation, but I thought it was a little alarming because you should not have a major amputation with CFA interventions for claudicants,” the vascular surgeon commented. “Really, do people care about a lymphatic leak or do they care about amputation? I think more needs to be fleshed out about what really happened in that case.”
He was also puzzled by the hospital lengths of stay: a mean of 3.2 days in the stent group and 6.3 days in the open surgery group. “I think those lengths of stay are astounding. Very high and unusual,” he observed.
Dr. Siracuse predicted that much-needed high-quality data comparing treatments of the CFA will be provided by the BEST-CLI trial (Best Endovascular versus Surgical Treatment for Critical Limb Ischemia), which has been updated to include both open and endovascular interventions.
He reported having no financial conflicts of interest regarding his presentation.
EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM