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Supreme Court allows partial travel ban to proceed
The U.S. Supreme Court has allowed a limited version of President Trump’s travel ban to move forward, prohibiting certain foreign nationals from six majority-Muslim countries from entering the country.
The justices’ June 26 order means that travelers from the affected countries who do not have a bona fide relationship with U.S. nationals or U.S. entities may not enter the United States. Conversely, it means that foreign physicians who have accepted a job at a U.S. institution or students who have been accepted to a U.S. medical school will be allowed to take those positions.
“In practical terms, this means that [the executive order] may not be enforced against foreign nationals who have a credible claim of a bona fide relationship with a person or entity in the United States,” justices wrote in their order. “All other foreign nationals are subject to the provisions. For individuals, a close familial relationship is required. A foreign national who wishes to enter the United States to live with or visit a family member ... clearly has such a relationship. As for entities, the relationship must be formal, documented, and formed in the ordinary course, rather than for the purpose of evading [the executive order].”
In a dissenting statement, Associate Justice Clarence Thomas wrote that the full ban should have gone into effect. Associate Justice Samuel Alito and Associate Justice Neil Gorsuch joined the dissent.
“I agree with the court’s implicit conclusion that the government has made a strong showing that it is likely to succeed on the merits – that is, that the [lower] judgments will be reversed,”Associate Justice Thomas wrote. “The government has also established that failure to stay the injunctions will cause irreparable harm by interfering with its compelling need to provide for the nation’s security. Finally, weighing the government’s interest in preserving national security against the hardships caused to respondents by temporary denials of entry into the country, the balance of the equities favors the government. I would thus grant the government’s applications for a stay in their entirety.”
President Trump’s revised executive order, signed March 6, bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from the affected countries from entering the U.S. for 120 days. The executive measure superseded President Trump’s original Jan. 27 travel ban. The revised order clarified that citizens of the six countries who are legal permanent U.S. residents or who have current visas to enter the country are exempt from the travel prohibition. Federal judges in Hawaii and Maryland ruled that the revised order was discriminatory and blocked the order from taking effect, a decision upheld by the 9th U.S. Circuit Court of Appeals.
Justices will hear oral arguments in the case this fall.
[email protected]
On Twitter @legal_med
The U.S. Supreme Court has allowed a limited version of President Trump’s travel ban to move forward, prohibiting certain foreign nationals from six majority-Muslim countries from entering the country.
The justices’ June 26 order means that travelers from the affected countries who do not have a bona fide relationship with U.S. nationals or U.S. entities may not enter the United States. Conversely, it means that foreign physicians who have accepted a job at a U.S. institution or students who have been accepted to a U.S. medical school will be allowed to take those positions.
“In practical terms, this means that [the executive order] may not be enforced against foreign nationals who have a credible claim of a bona fide relationship with a person or entity in the United States,” justices wrote in their order. “All other foreign nationals are subject to the provisions. For individuals, a close familial relationship is required. A foreign national who wishes to enter the United States to live with or visit a family member ... clearly has such a relationship. As for entities, the relationship must be formal, documented, and formed in the ordinary course, rather than for the purpose of evading [the executive order].”
In a dissenting statement, Associate Justice Clarence Thomas wrote that the full ban should have gone into effect. Associate Justice Samuel Alito and Associate Justice Neil Gorsuch joined the dissent.
“I agree with the court’s implicit conclusion that the government has made a strong showing that it is likely to succeed on the merits – that is, that the [lower] judgments will be reversed,”Associate Justice Thomas wrote. “The government has also established that failure to stay the injunctions will cause irreparable harm by interfering with its compelling need to provide for the nation’s security. Finally, weighing the government’s interest in preserving national security against the hardships caused to respondents by temporary denials of entry into the country, the balance of the equities favors the government. I would thus grant the government’s applications for a stay in their entirety.”
President Trump’s revised executive order, signed March 6, bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from the affected countries from entering the U.S. for 120 days. The executive measure superseded President Trump’s original Jan. 27 travel ban. The revised order clarified that citizens of the six countries who are legal permanent U.S. residents or who have current visas to enter the country are exempt from the travel prohibition. Federal judges in Hawaii and Maryland ruled that the revised order was discriminatory and blocked the order from taking effect, a decision upheld by the 9th U.S. Circuit Court of Appeals.
Justices will hear oral arguments in the case this fall.
[email protected]
On Twitter @legal_med
The U.S. Supreme Court has allowed a limited version of President Trump’s travel ban to move forward, prohibiting certain foreign nationals from six majority-Muslim countries from entering the country.
The justices’ June 26 order means that travelers from the affected countries who do not have a bona fide relationship with U.S. nationals or U.S. entities may not enter the United States. Conversely, it means that foreign physicians who have accepted a job at a U.S. institution or students who have been accepted to a U.S. medical school will be allowed to take those positions.
“In practical terms, this means that [the executive order] may not be enforced against foreign nationals who have a credible claim of a bona fide relationship with a person or entity in the United States,” justices wrote in their order. “All other foreign nationals are subject to the provisions. For individuals, a close familial relationship is required. A foreign national who wishes to enter the United States to live with or visit a family member ... clearly has such a relationship. As for entities, the relationship must be formal, documented, and formed in the ordinary course, rather than for the purpose of evading [the executive order].”
In a dissenting statement, Associate Justice Clarence Thomas wrote that the full ban should have gone into effect. Associate Justice Samuel Alito and Associate Justice Neil Gorsuch joined the dissent.
“I agree with the court’s implicit conclusion that the government has made a strong showing that it is likely to succeed on the merits – that is, that the [lower] judgments will be reversed,”Associate Justice Thomas wrote. “The government has also established that failure to stay the injunctions will cause irreparable harm by interfering with its compelling need to provide for the nation’s security. Finally, weighing the government’s interest in preserving national security against the hardships caused to respondents by temporary denials of entry into the country, the balance of the equities favors the government. I would thus grant the government’s applications for a stay in their entirety.”
President Trump’s revised executive order, signed March 6, bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from the affected countries from entering the U.S. for 120 days. The executive measure superseded President Trump’s original Jan. 27 travel ban. The revised order clarified that citizens of the six countries who are legal permanent U.S. residents or who have current visas to enter the country are exempt from the travel prohibition. Federal judges in Hawaii and Maryland ruled that the revised order was discriminatory and blocked the order from taking effect, a decision upheld by the 9th U.S. Circuit Court of Appeals.
Justices will hear oral arguments in the case this fall.
[email protected]
On Twitter @legal_med
Pembrolizumab + rituximab boost response rates in relapsed follicular lymphoma
LUGANO, SWITZERLAND – A novel combination of the anti-programmed death 1 (PD-1) checkpoint inhibitor pembrolizumab (Keytruda) and the anti-CD20 monoclonal antibody rituximab was associated with a high overall response rate (ORR) in patients with relapsed follicular lymphoma in a phase II clinical trial.
Among 20 patients evaluable for efficacy, the overall response rate to the combination was 65%, including 50% complete responses (CR) reported Loretta J. Nastoupil, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Follicular lymphoma is probably one of the best examples of targeting the immune system and also one of the earliest examples. Over the last few years we’ve learned a great deal about the different mechanisms of not only negative impact on infiltrating T cells, but also immune escape and T-cell exhaustion,” she said at the International Conference on Malignant Lymphoma.
Although biopsies of follicular lymphoma tumors have demonstrated infiltration of anti-tumor T cells, these cells are typically impeded by immune checkpoints, including PD-1 and its ligand (PD-L1).
The use of anti-PD-1 checkpoint inhibitors such as pembrolizumab has been shown to enhance the function of antitumor T cells in follicular lymphoma, and blocking PD-1 on natural killer cells enhances the antibody-dependent cell-mediated cytotoxicity of the natural killer cells, she said.
Because rituximab, a mainstay of therapy for non-Hodgkin lymphomas, induces antibody-dependent cell-mediated cytotoxicity, the investigators reasoned that combining it with pembrolizumab would simultaneously and synergistically stimulate activation of innate and adaptive immunity.
They designed a phase II, single-arm study in 30 patients with relapsed follicular lymphoma following one or more prior lines of therapy. The patients also had to have rituximab-sensitive disease, defined as a complete response (CR) or partial response lasting for at least 6 months following the most recent rituximab-containing therapy.
The patients were treated with rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, and pembrolizumab 200 mg IV every 3 weeks for up to 16 cycles starting on day 2 of cycle 1.
The investigators expected that the combination would improve ORR, the primary endpoint, to at least 60%, compared with 40% for historical controls treated with repeat courses of rituximab.
At the data cutoff for the interim analysis, 32 patients had been enrolled, 30 were evaluable for safety, and 20 for efficacy after a median follow-up of 8.2 months.
Among the 20 patients (median age 64) in the efficacy analysis, 10 (50%) had a CR, and 3 (15%) had a partial response, for an ORR of 65%. Three additional patients had stable disease, and four had disease progression as best responses.
Among the patients with CRs, the duration of response ranged from nearly 275 days to more than 600 days.
“This does appear to be durable, and it is time dependent in terms of response. We did see early response, and we also saw deepening of response over time,” Dr. Nastoupil said.
Four patients were discontinued from the study because of immune-related adverse events. All four patients had achieved a CR at the time of study removal, and all four have ongoing CRs.
Among the 30 patients evaluable for safety, there were no grade 4 adverse events, no deaths, and few grade 3 events. Most events were grade 1 or 2, and included fatigue, eye pain/blurred vision/watery eye, nausea and vomiting, diarrhea dyspnea, rash, cough, and lymphopenia.
The investigators also looked at potential biomarkers for response, including PD-L1 expression in tumors prior to treatment. They found in samples from three patients who went on to achieve CRs that PD-L1 expression in tumor cells was low, ranging from 0% to 8%, suggesting that PD-L1 expression may not be necessary to generate a response with the combination.
They then looked at the association between CD8-positive T effector cells and responses in 12 patients, and found that patients with higher levels of expression had better ORR and CR rates.
“These interim results warrant further investigation of this combination in follicular lymphoma, and an expansion to include patients with refractory follicular lymphoma is planned,” Dr. Nastoupil concluded.
The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.
LUGANO, SWITZERLAND – A novel combination of the anti-programmed death 1 (PD-1) checkpoint inhibitor pembrolizumab (Keytruda) and the anti-CD20 monoclonal antibody rituximab was associated with a high overall response rate (ORR) in patients with relapsed follicular lymphoma in a phase II clinical trial.
Among 20 patients evaluable for efficacy, the overall response rate to the combination was 65%, including 50% complete responses (CR) reported Loretta J. Nastoupil, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Follicular lymphoma is probably one of the best examples of targeting the immune system and also one of the earliest examples. Over the last few years we’ve learned a great deal about the different mechanisms of not only negative impact on infiltrating T cells, but also immune escape and T-cell exhaustion,” she said at the International Conference on Malignant Lymphoma.
Although biopsies of follicular lymphoma tumors have demonstrated infiltration of anti-tumor T cells, these cells are typically impeded by immune checkpoints, including PD-1 and its ligand (PD-L1).
The use of anti-PD-1 checkpoint inhibitors such as pembrolizumab has been shown to enhance the function of antitumor T cells in follicular lymphoma, and blocking PD-1 on natural killer cells enhances the antibody-dependent cell-mediated cytotoxicity of the natural killer cells, she said.
Because rituximab, a mainstay of therapy for non-Hodgkin lymphomas, induces antibody-dependent cell-mediated cytotoxicity, the investigators reasoned that combining it with pembrolizumab would simultaneously and synergistically stimulate activation of innate and adaptive immunity.
They designed a phase II, single-arm study in 30 patients with relapsed follicular lymphoma following one or more prior lines of therapy. The patients also had to have rituximab-sensitive disease, defined as a complete response (CR) or partial response lasting for at least 6 months following the most recent rituximab-containing therapy.
The patients were treated with rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, and pembrolizumab 200 mg IV every 3 weeks for up to 16 cycles starting on day 2 of cycle 1.
The investigators expected that the combination would improve ORR, the primary endpoint, to at least 60%, compared with 40% for historical controls treated with repeat courses of rituximab.
At the data cutoff for the interim analysis, 32 patients had been enrolled, 30 were evaluable for safety, and 20 for efficacy after a median follow-up of 8.2 months.
Among the 20 patients (median age 64) in the efficacy analysis, 10 (50%) had a CR, and 3 (15%) had a partial response, for an ORR of 65%. Three additional patients had stable disease, and four had disease progression as best responses.
Among the patients with CRs, the duration of response ranged from nearly 275 days to more than 600 days.
“This does appear to be durable, and it is time dependent in terms of response. We did see early response, and we also saw deepening of response over time,” Dr. Nastoupil said.
Four patients were discontinued from the study because of immune-related adverse events. All four patients had achieved a CR at the time of study removal, and all four have ongoing CRs.
Among the 30 patients evaluable for safety, there were no grade 4 adverse events, no deaths, and few grade 3 events. Most events were grade 1 or 2, and included fatigue, eye pain/blurred vision/watery eye, nausea and vomiting, diarrhea dyspnea, rash, cough, and lymphopenia.
The investigators also looked at potential biomarkers for response, including PD-L1 expression in tumors prior to treatment. They found in samples from three patients who went on to achieve CRs that PD-L1 expression in tumor cells was low, ranging from 0% to 8%, suggesting that PD-L1 expression may not be necessary to generate a response with the combination.
They then looked at the association between CD8-positive T effector cells and responses in 12 patients, and found that patients with higher levels of expression had better ORR and CR rates.
“These interim results warrant further investigation of this combination in follicular lymphoma, and an expansion to include patients with refractory follicular lymphoma is planned,” Dr. Nastoupil concluded.
The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.
LUGANO, SWITZERLAND – A novel combination of the anti-programmed death 1 (PD-1) checkpoint inhibitor pembrolizumab (Keytruda) and the anti-CD20 monoclonal antibody rituximab was associated with a high overall response rate (ORR) in patients with relapsed follicular lymphoma in a phase II clinical trial.
Among 20 patients evaluable for efficacy, the overall response rate to the combination was 65%, including 50% complete responses (CR) reported Loretta J. Nastoupil, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Follicular lymphoma is probably one of the best examples of targeting the immune system and also one of the earliest examples. Over the last few years we’ve learned a great deal about the different mechanisms of not only negative impact on infiltrating T cells, but also immune escape and T-cell exhaustion,” she said at the International Conference on Malignant Lymphoma.
Although biopsies of follicular lymphoma tumors have demonstrated infiltration of anti-tumor T cells, these cells are typically impeded by immune checkpoints, including PD-1 and its ligand (PD-L1).
The use of anti-PD-1 checkpoint inhibitors such as pembrolizumab has been shown to enhance the function of antitumor T cells in follicular lymphoma, and blocking PD-1 on natural killer cells enhances the antibody-dependent cell-mediated cytotoxicity of the natural killer cells, she said.
Because rituximab, a mainstay of therapy for non-Hodgkin lymphomas, induces antibody-dependent cell-mediated cytotoxicity, the investigators reasoned that combining it with pembrolizumab would simultaneously and synergistically stimulate activation of innate and adaptive immunity.
They designed a phase II, single-arm study in 30 patients with relapsed follicular lymphoma following one or more prior lines of therapy. The patients also had to have rituximab-sensitive disease, defined as a complete response (CR) or partial response lasting for at least 6 months following the most recent rituximab-containing therapy.
The patients were treated with rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, and pembrolizumab 200 mg IV every 3 weeks for up to 16 cycles starting on day 2 of cycle 1.
The investigators expected that the combination would improve ORR, the primary endpoint, to at least 60%, compared with 40% for historical controls treated with repeat courses of rituximab.
At the data cutoff for the interim analysis, 32 patients had been enrolled, 30 were evaluable for safety, and 20 for efficacy after a median follow-up of 8.2 months.
Among the 20 patients (median age 64) in the efficacy analysis, 10 (50%) had a CR, and 3 (15%) had a partial response, for an ORR of 65%. Three additional patients had stable disease, and four had disease progression as best responses.
Among the patients with CRs, the duration of response ranged from nearly 275 days to more than 600 days.
“This does appear to be durable, and it is time dependent in terms of response. We did see early response, and we also saw deepening of response over time,” Dr. Nastoupil said.
Four patients were discontinued from the study because of immune-related adverse events. All four patients had achieved a CR at the time of study removal, and all four have ongoing CRs.
Among the 30 patients evaluable for safety, there were no grade 4 adverse events, no deaths, and few grade 3 events. Most events were grade 1 or 2, and included fatigue, eye pain/blurred vision/watery eye, nausea and vomiting, diarrhea dyspnea, rash, cough, and lymphopenia.
The investigators also looked at potential biomarkers for response, including PD-L1 expression in tumors prior to treatment. They found in samples from three patients who went on to achieve CRs that PD-L1 expression in tumor cells was low, ranging from 0% to 8%, suggesting that PD-L1 expression may not be necessary to generate a response with the combination.
They then looked at the association between CD8-positive T effector cells and responses in 12 patients, and found that patients with higher levels of expression had better ORR and CR rates.
“These interim results warrant further investigation of this combination in follicular lymphoma, and an expansion to include patients with refractory follicular lymphoma is planned,” Dr. Nastoupil concluded.
The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.
AT 14-ICML
Key clinical point: The combination of pembrolizumab and rituximab increased responses compared with repeat rituximab in patients with relapsed follicular lymphoma.
Major finding: The overall response rate with the combination was 65%, including 50% complete responses.
Data source: Open-label, phase II, single-arm study in 32 patients with relapsed follicular lymphoma (20 for efficacy, 30 for safety analysis).
Disclosures: The Leukemia & Lymphoma Society supported the study. Dr Nastoupil has disclosed consulting fees from Celgene and contracted research for Abbvie, Janssen, and TG Therapeutics.
Updated Analysis of Ocrelizumab’s Safety
NEW ORLEANS—The safety profile of ocrelizumab in ongoing open-label extension studies in relapsing multiple sclerosis (MS) and primary progressive MS is generally consistent with that observed in controlled clinical trials, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC). “A slight increase in the rate of serious infections was observed in patients with relapsing MS beyond two years, but the rates remained low,” reported Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland, and colleagues. “This was not observed in patients with primary progressive MS, and additional exposure data are needed to determine if the risk increases with further dosing,” the researchers said. “Incidence rates of malignancies and breast cancer observed with ocrelizumab treatment in MS remain within the range of epidemiologic background data.”
The safety and efficacy of ocrelizumab previously have been characterized in a phase II study in patients with relapsing-remitting MS and in phase III studies in patients with relapsing MS (OPERA I and OPERA II) and in patients with primary progressive MS (ORATORIO). Results from these trials showed that ocrelizumab reduced clinical and MRI evidence of disease activity, compared with placebo and interferon beta-1a. The most common adverse events associated with ocrelizumab during the double-blind periods of the phase III trials included infusion-related reactions, nasopharyngitis, upper respiratory tract infections, headache, and urinary tract infections. During the double-blind treatment period in the phase III trials in relapsing MS, serious adverse events, serious infections, and malignancies were reported in 6.9%, 1.3%, and 0.5% of ocrelizumab-treated patients, respectively (vs 8.7%, 2.9%, and 0.2% of patients treated with interferon beta-1a). In the phase III trial in primary progressive MS, these events were reported in 20.4%, 6.2%, and 2.3% of ocrelizumab-treated patients (vs 22.2%, 5.9%, and 0.8% of patients who received placebo). Across studies, few patients who received ocrelizumab (in the range of 2% to 4%) had adverse event–related treatment withdrawals.
At the CMSC annual meeting, data from controlled and open-label extension periods of the clinical trials of ocrelizumab in relapsing MS and primary progressive MS were presented.
Upon completion of a double-blind treatment period, patients from all studies were eligible to enter a long-term open-label extension in which they received ocrelizumab treatment. Safety analyses were based on integrated data from the phase II and phase III studies. The primary analysis was based on the clinical cutoff dates of the individual studies (phase II, January 22, 2015; OPERA I, April 2, 2015; OPERA II, May 12, 2015; ORATORIO, July 24, 2015). The present updated analysis includes all patients who received one or more dose of ocrelizumab during the controlled or open-label periods of the phase II and phase III studies (ie, the ocrelizumab all-exposure population) as of January 20, 2016. Additional data cutoffs of June 30, 2016, and September 15, 2016, were presented for malignancies to demonstrate changes with increasing ocrelizumab exposure.
The ocrelizumab all-exposure group included 2,279 patients. Patients’ mean age was 40.1, and 61.3% were female. Time since MS symptom onset was 6.67 years, and time since MS diagnosis was 3.66 years.
Overall Adverse Events
As of January 20, 2016, the majority (81%) of patients who received ocrelizumab experienced at least one adverse event, corresponding to a rate of 242 events per 100 patient-years. The most common adverse events included nasopharyngitis, upper respiratory tract infection, urinary tract infection, infusion-related reactions, and headache. Serious adverse events were reported in 12% of patients, corresponding to 6.97 events per 100 patient-years, and most commonly included infections. Treatment withdrawal because of an adverse event occurred in 3.3% of patients (rate, 1.40 per 100 patient-years) and primarily included infusion-related reactions (0.9%) and events coded as neoplasms (0.6%) or infections (0.4%).
Infections
As of January 20, 2016, 56.9% of the ocrelizumab all-exposure population reported one or more infection with ocrelizumab, corresponding to a rate of 73.6 per 100 patient-years. “These findings are consistent with the 75.6 rate observed at the primary analysis cutoff date,” the researchers reported. Infections were reported at the highest rate following the first dose and declined with subsequent dosing. Infections reported in 5% or more of patients included nasopharyngitis, upper respiratory tract infection, urinary tract infection, bronchitis, and influenza. In the ocrelizumab all-exposure population, the rate per 100 patient-years of serious infections (1.80) as of January 20, 2016, was comparable with the rate at the primary analysis cutoff date (1.74). Data for the pooled relapsing MS population showed a slight increase in the rate per 100 patient-years of serious infections (1.45) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (1.08); “however, rates remained low, and further exposure is needed to make any interpretation,” the researchers said.
Among patients with primary progressive MS, the rate per 100 patient-years of serious infections remained stable (2.74) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (2.97). The most common serious infection reported was pneumonia. No infections were identified as opportunistic in nature.
Malignancies
In the MS clinical trial program, an imbalance in the crude incidence of malignancies was observed between the ocrelizumab- and comparator-treated patients, which was associated with a cluster of breast cancer events in the ocrelizumab group. Over time, the crude incidence rate of malignancy per 100 patient-years in the ocrelizumab all-exposure population fluctuated but remained within the epidemiologic range of patients with MS. An observed change in the crude incidence rate of malignancy from June to September is attributed to the crude incidence rate of non-melanoma skin cancer, which increased from 0.090 at the primary analysis cutoff date to 0.145 at the September 15, 2016, data cutoff, due to six new cases of basal cell carcinoma. The crude incidence rate of breast cancer remained stable through the September 15, 2016, data cutoff.
More Recent Developments
In late May 2017, Genentech, the maker of ocrelizumab, notified physicians of
—Glenn S. Williams
NEW ORLEANS—The safety profile of ocrelizumab in ongoing open-label extension studies in relapsing multiple sclerosis (MS) and primary progressive MS is generally consistent with that observed in controlled clinical trials, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC). “A slight increase in the rate of serious infections was observed in patients with relapsing MS beyond two years, but the rates remained low,” reported Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland, and colleagues. “This was not observed in patients with primary progressive MS, and additional exposure data are needed to determine if the risk increases with further dosing,” the researchers said. “Incidence rates of malignancies and breast cancer observed with ocrelizumab treatment in MS remain within the range of epidemiologic background data.”
The safety and efficacy of ocrelizumab previously have been characterized in a phase II study in patients with relapsing-remitting MS and in phase III studies in patients with relapsing MS (OPERA I and OPERA II) and in patients with primary progressive MS (ORATORIO). Results from these trials showed that ocrelizumab reduced clinical and MRI evidence of disease activity, compared with placebo and interferon beta-1a. The most common adverse events associated with ocrelizumab during the double-blind periods of the phase III trials included infusion-related reactions, nasopharyngitis, upper respiratory tract infections, headache, and urinary tract infections. During the double-blind treatment period in the phase III trials in relapsing MS, serious adverse events, serious infections, and malignancies were reported in 6.9%, 1.3%, and 0.5% of ocrelizumab-treated patients, respectively (vs 8.7%, 2.9%, and 0.2% of patients treated with interferon beta-1a). In the phase III trial in primary progressive MS, these events were reported in 20.4%, 6.2%, and 2.3% of ocrelizumab-treated patients (vs 22.2%, 5.9%, and 0.8% of patients who received placebo). Across studies, few patients who received ocrelizumab (in the range of 2% to 4%) had adverse event–related treatment withdrawals.
At the CMSC annual meeting, data from controlled and open-label extension periods of the clinical trials of ocrelizumab in relapsing MS and primary progressive MS were presented.
Upon completion of a double-blind treatment period, patients from all studies were eligible to enter a long-term open-label extension in which they received ocrelizumab treatment. Safety analyses were based on integrated data from the phase II and phase III studies. The primary analysis was based on the clinical cutoff dates of the individual studies (phase II, January 22, 2015; OPERA I, April 2, 2015; OPERA II, May 12, 2015; ORATORIO, July 24, 2015). The present updated analysis includes all patients who received one or more dose of ocrelizumab during the controlled or open-label periods of the phase II and phase III studies (ie, the ocrelizumab all-exposure population) as of January 20, 2016. Additional data cutoffs of June 30, 2016, and September 15, 2016, were presented for malignancies to demonstrate changes with increasing ocrelizumab exposure.
The ocrelizumab all-exposure group included 2,279 patients. Patients’ mean age was 40.1, and 61.3% were female. Time since MS symptom onset was 6.67 years, and time since MS diagnosis was 3.66 years.
Overall Adverse Events
As of January 20, 2016, the majority (81%) of patients who received ocrelizumab experienced at least one adverse event, corresponding to a rate of 242 events per 100 patient-years. The most common adverse events included nasopharyngitis, upper respiratory tract infection, urinary tract infection, infusion-related reactions, and headache. Serious adverse events were reported in 12% of patients, corresponding to 6.97 events per 100 patient-years, and most commonly included infections. Treatment withdrawal because of an adverse event occurred in 3.3% of patients (rate, 1.40 per 100 patient-years) and primarily included infusion-related reactions (0.9%) and events coded as neoplasms (0.6%) or infections (0.4%).
Infections
As of January 20, 2016, 56.9% of the ocrelizumab all-exposure population reported one or more infection with ocrelizumab, corresponding to a rate of 73.6 per 100 patient-years. “These findings are consistent with the 75.6 rate observed at the primary analysis cutoff date,” the researchers reported. Infections were reported at the highest rate following the first dose and declined with subsequent dosing. Infections reported in 5% or more of patients included nasopharyngitis, upper respiratory tract infection, urinary tract infection, bronchitis, and influenza. In the ocrelizumab all-exposure population, the rate per 100 patient-years of serious infections (1.80) as of January 20, 2016, was comparable with the rate at the primary analysis cutoff date (1.74). Data for the pooled relapsing MS population showed a slight increase in the rate per 100 patient-years of serious infections (1.45) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (1.08); “however, rates remained low, and further exposure is needed to make any interpretation,” the researchers said.
Among patients with primary progressive MS, the rate per 100 patient-years of serious infections remained stable (2.74) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (2.97). The most common serious infection reported was pneumonia. No infections were identified as opportunistic in nature.
Malignancies
In the MS clinical trial program, an imbalance in the crude incidence of malignancies was observed between the ocrelizumab- and comparator-treated patients, which was associated with a cluster of breast cancer events in the ocrelizumab group. Over time, the crude incidence rate of malignancy per 100 patient-years in the ocrelizumab all-exposure population fluctuated but remained within the epidemiologic range of patients with MS. An observed change in the crude incidence rate of malignancy from June to September is attributed to the crude incidence rate of non-melanoma skin cancer, which increased from 0.090 at the primary analysis cutoff date to 0.145 at the September 15, 2016, data cutoff, due to six new cases of basal cell carcinoma. The crude incidence rate of breast cancer remained stable through the September 15, 2016, data cutoff.
More Recent Developments
In late May 2017, Genentech, the maker of ocrelizumab, notified physicians of
—Glenn S. Williams
NEW ORLEANS—The safety profile of ocrelizumab in ongoing open-label extension studies in relapsing multiple sclerosis (MS) and primary progressive MS is generally consistent with that observed in controlled clinical trials, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC). “A slight increase in the rate of serious infections was observed in patients with relapsing MS beyond two years, but the rates remained low,” reported Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland, and colleagues. “This was not observed in patients with primary progressive MS, and additional exposure data are needed to determine if the risk increases with further dosing,” the researchers said. “Incidence rates of malignancies and breast cancer observed with ocrelizumab treatment in MS remain within the range of epidemiologic background data.”
The safety and efficacy of ocrelizumab previously have been characterized in a phase II study in patients with relapsing-remitting MS and in phase III studies in patients with relapsing MS (OPERA I and OPERA II) and in patients with primary progressive MS (ORATORIO). Results from these trials showed that ocrelizumab reduced clinical and MRI evidence of disease activity, compared with placebo and interferon beta-1a. The most common adverse events associated with ocrelizumab during the double-blind periods of the phase III trials included infusion-related reactions, nasopharyngitis, upper respiratory tract infections, headache, and urinary tract infections. During the double-blind treatment period in the phase III trials in relapsing MS, serious adverse events, serious infections, and malignancies were reported in 6.9%, 1.3%, and 0.5% of ocrelizumab-treated patients, respectively (vs 8.7%, 2.9%, and 0.2% of patients treated with interferon beta-1a). In the phase III trial in primary progressive MS, these events were reported in 20.4%, 6.2%, and 2.3% of ocrelizumab-treated patients (vs 22.2%, 5.9%, and 0.8% of patients who received placebo). Across studies, few patients who received ocrelizumab (in the range of 2% to 4%) had adverse event–related treatment withdrawals.
At the CMSC annual meeting, data from controlled and open-label extension periods of the clinical trials of ocrelizumab in relapsing MS and primary progressive MS were presented.
Upon completion of a double-blind treatment period, patients from all studies were eligible to enter a long-term open-label extension in which they received ocrelizumab treatment. Safety analyses were based on integrated data from the phase II and phase III studies. The primary analysis was based on the clinical cutoff dates of the individual studies (phase II, January 22, 2015; OPERA I, April 2, 2015; OPERA II, May 12, 2015; ORATORIO, July 24, 2015). The present updated analysis includes all patients who received one or more dose of ocrelizumab during the controlled or open-label periods of the phase II and phase III studies (ie, the ocrelizumab all-exposure population) as of January 20, 2016. Additional data cutoffs of June 30, 2016, and September 15, 2016, were presented for malignancies to demonstrate changes with increasing ocrelizumab exposure.
The ocrelizumab all-exposure group included 2,279 patients. Patients’ mean age was 40.1, and 61.3% were female. Time since MS symptom onset was 6.67 years, and time since MS diagnosis was 3.66 years.
Overall Adverse Events
As of January 20, 2016, the majority (81%) of patients who received ocrelizumab experienced at least one adverse event, corresponding to a rate of 242 events per 100 patient-years. The most common adverse events included nasopharyngitis, upper respiratory tract infection, urinary tract infection, infusion-related reactions, and headache. Serious adverse events were reported in 12% of patients, corresponding to 6.97 events per 100 patient-years, and most commonly included infections. Treatment withdrawal because of an adverse event occurred in 3.3% of patients (rate, 1.40 per 100 patient-years) and primarily included infusion-related reactions (0.9%) and events coded as neoplasms (0.6%) or infections (0.4%).
Infections
As of January 20, 2016, 56.9% of the ocrelizumab all-exposure population reported one or more infection with ocrelizumab, corresponding to a rate of 73.6 per 100 patient-years. “These findings are consistent with the 75.6 rate observed at the primary analysis cutoff date,” the researchers reported. Infections were reported at the highest rate following the first dose and declined with subsequent dosing. Infections reported in 5% or more of patients included nasopharyngitis, upper respiratory tract infection, urinary tract infection, bronchitis, and influenza. In the ocrelizumab all-exposure population, the rate per 100 patient-years of serious infections (1.80) as of January 20, 2016, was comparable with the rate at the primary analysis cutoff date (1.74). Data for the pooled relapsing MS population showed a slight increase in the rate per 100 patient-years of serious infections (1.45) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (1.08); “however, rates remained low, and further exposure is needed to make any interpretation,” the researchers said.
Among patients with primary progressive MS, the rate per 100 patient-years of serious infections remained stable (2.74) as of January 20, 2016, compared with the rate at the primary analysis cutoff date (2.97). The most common serious infection reported was pneumonia. No infections were identified as opportunistic in nature.
Malignancies
In the MS clinical trial program, an imbalance in the crude incidence of malignancies was observed between the ocrelizumab- and comparator-treated patients, which was associated with a cluster of breast cancer events in the ocrelizumab group. Over time, the crude incidence rate of malignancy per 100 patient-years in the ocrelizumab all-exposure population fluctuated but remained within the epidemiologic range of patients with MS. An observed change in the crude incidence rate of malignancy from June to September is attributed to the crude incidence rate of non-melanoma skin cancer, which increased from 0.090 at the primary analysis cutoff date to 0.145 at the September 15, 2016, data cutoff, due to six new cases of basal cell carcinoma. The crude incidence rate of breast cancer remained stable through the September 15, 2016, data cutoff.
More Recent Developments
In late May 2017, Genentech, the maker of ocrelizumab, notified physicians of
—Glenn S. Williams
New Tool Can Distinguish Between Tremor Syndromes
A new tool called the tremor stability index (TSI) can aid the differential diagnosis of essential tremor and Parkinson’s disease, according to research published online ahead of print April 27 in Brain. The TSI has a diagnostic accuracy of approximately 90% for these syndromes, and neurologists can derive it from brief, inexpensive, and noninvasive tremor recordings.
Misdiagnosis of tremor syndromes is common and affects clinical care and research. The current gold standard for diagnosis is clinical evaluation by a specialist in movement disorders. In 2015, Brittain et al found that the frequency of tremor remains stable over a narrow range of frequencies in essential tremor, but remains stable over a broader range in Parkinson’s disease.
Lazzaro di Biase, PhD, a postdoctoral researcher at Università Campus Bio-Medico in Rome, and colleagues analyzed the overall tremor stability characteristics of essential tremor and Parkinson’s disease to develop the TSI, an interquartile range of the change in tremor frequency. The investigators performed kinematic measurements on a test cohort of 16 patients with tremor-dominant Parkinson’s disease and 20 patients with essential tremor. Data were collected after overnight withdrawal of medications. A validation cohort included new and original data taken from published studies and encompassed 42 rest tremor recordings of patients with Parkinson’s disease and eight postural tremor recordings of patients with essential tremor.
In the test cohort, Dr. di Biase and colleagues found no difference in mean instantaneous frequency between patient groups, but saw a difference in TSI between groups. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 14.8. The optimal TSI threshold in the test cohort was 1.05; TSI values greater than 1.05 indicated a diagnosis of essential tremor, and TSI values of 1.05 or less indicated a diagnosis of Parkinson’s disease. Follow-up recordings made one year and seven months later confirmed the stability of the TSI over time for patients with Parkinson’s disease.
The investigators found a difference in mean instantaneous frequency between groups in the validation cohort, as well as a significant difference in TSI between essential tremor and Parkinson’s disease. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 5.7. When the researchers applied the threshold of 1.05, they found that the TSI had excellent discriminatory ability. In addition, bootstrap analysis revealed that the TSI outperformed the mean harmonic power of postural tremor harmonics 72% of the time.
The TSI was robust when applied to various patient groups with differing demographics and clinical characteristics. The devices used to record tremor did not affect the TSI’s reliability, nor did postural context. According to the researchers, the TSI can be rapidly estimated from 10-second recordings of tremor.
“The TSI provides a promising diagnostic aid in clinical practice and could be a useful tool to avoid selection errors in clinical trials,” said Dr. di Biase. “It will be important to see if this index can also distinguish dystonic tremor, which may masquerade as Parkinson’s disease or essential tremor,” he added.
—Erik Greb
Suggested Reading
di Biase L, Brittain JS, Shah SA, et al. Tremor stability index: a new tool for differential diagnosis in tremor syndromes. Brain. 2017 Apr 27 [Epub ahead of print].
A new tool called the tremor stability index (TSI) can aid the differential diagnosis of essential tremor and Parkinson’s disease, according to research published online ahead of print April 27 in Brain. The TSI has a diagnostic accuracy of approximately 90% for these syndromes, and neurologists can derive it from brief, inexpensive, and noninvasive tremor recordings.
Misdiagnosis of tremor syndromes is common and affects clinical care and research. The current gold standard for diagnosis is clinical evaluation by a specialist in movement disorders. In 2015, Brittain et al found that the frequency of tremor remains stable over a narrow range of frequencies in essential tremor, but remains stable over a broader range in Parkinson’s disease.
Lazzaro di Biase, PhD, a postdoctoral researcher at Università Campus Bio-Medico in Rome, and colleagues analyzed the overall tremor stability characteristics of essential tremor and Parkinson’s disease to develop the TSI, an interquartile range of the change in tremor frequency. The investigators performed kinematic measurements on a test cohort of 16 patients with tremor-dominant Parkinson’s disease and 20 patients with essential tremor. Data were collected after overnight withdrawal of medications. A validation cohort included new and original data taken from published studies and encompassed 42 rest tremor recordings of patients with Parkinson’s disease and eight postural tremor recordings of patients with essential tremor.
In the test cohort, Dr. di Biase and colleagues found no difference in mean instantaneous frequency between patient groups, but saw a difference in TSI between groups. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 14.8. The optimal TSI threshold in the test cohort was 1.05; TSI values greater than 1.05 indicated a diagnosis of essential tremor, and TSI values of 1.05 or less indicated a diagnosis of Parkinson’s disease. Follow-up recordings made one year and seven months later confirmed the stability of the TSI over time for patients with Parkinson’s disease.
The investigators found a difference in mean instantaneous frequency between groups in the validation cohort, as well as a significant difference in TSI between essential tremor and Parkinson’s disease. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 5.7. When the researchers applied the threshold of 1.05, they found that the TSI had excellent discriminatory ability. In addition, bootstrap analysis revealed that the TSI outperformed the mean harmonic power of postural tremor harmonics 72% of the time.
The TSI was robust when applied to various patient groups with differing demographics and clinical characteristics. The devices used to record tremor did not affect the TSI’s reliability, nor did postural context. According to the researchers, the TSI can be rapidly estimated from 10-second recordings of tremor.
“The TSI provides a promising diagnostic aid in clinical practice and could be a useful tool to avoid selection errors in clinical trials,” said Dr. di Biase. “It will be important to see if this index can also distinguish dystonic tremor, which may masquerade as Parkinson’s disease or essential tremor,” he added.
—Erik Greb
Suggested Reading
di Biase L, Brittain JS, Shah SA, et al. Tremor stability index: a new tool for differential diagnosis in tremor syndromes. Brain. 2017 Apr 27 [Epub ahead of print].
A new tool called the tremor stability index (TSI) can aid the differential diagnosis of essential tremor and Parkinson’s disease, according to research published online ahead of print April 27 in Brain. The TSI has a diagnostic accuracy of approximately 90% for these syndromes, and neurologists can derive it from brief, inexpensive, and noninvasive tremor recordings.
Misdiagnosis of tremor syndromes is common and affects clinical care and research. The current gold standard for diagnosis is clinical evaluation by a specialist in movement disorders. In 2015, Brittain et al found that the frequency of tremor remains stable over a narrow range of frequencies in essential tremor, but remains stable over a broader range in Parkinson’s disease.
Lazzaro di Biase, PhD, a postdoctoral researcher at Università Campus Bio-Medico in Rome, and colleagues analyzed the overall tremor stability characteristics of essential tremor and Parkinson’s disease to develop the TSI, an interquartile range of the change in tremor frequency. The investigators performed kinematic measurements on a test cohort of 16 patients with tremor-dominant Parkinson’s disease and 20 patients with essential tremor. Data were collected after overnight withdrawal of medications. A validation cohort included new and original data taken from published studies and encompassed 42 rest tremor recordings of patients with Parkinson’s disease and eight postural tremor recordings of patients with essential tremor.
In the test cohort, Dr. di Biase and colleagues found no difference in mean instantaneous frequency between patient groups, but saw a difference in TSI between groups. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 14.8. The optimal TSI threshold in the test cohort was 1.05; TSI values greater than 1.05 indicated a diagnosis of essential tremor, and TSI values of 1.05 or less indicated a diagnosis of Parkinson’s disease. Follow-up recordings made one year and seven months later confirmed the stability of the TSI over time for patients with Parkinson’s disease.
The investigators found a difference in mean instantaneous frequency between groups in the validation cohort, as well as a significant difference in TSI between essential tremor and Parkinson’s disease. For every unit increase in TSI, the odds of a patient having a diagnosis of essential tremor increased by a factor of 5.7. When the researchers applied the threshold of 1.05, they found that the TSI had excellent discriminatory ability. In addition, bootstrap analysis revealed that the TSI outperformed the mean harmonic power of postural tremor harmonics 72% of the time.
The TSI was robust when applied to various patient groups with differing demographics and clinical characteristics. The devices used to record tremor did not affect the TSI’s reliability, nor did postural context. According to the researchers, the TSI can be rapidly estimated from 10-second recordings of tremor.
“The TSI provides a promising diagnostic aid in clinical practice and could be a useful tool to avoid selection errors in clinical trials,” said Dr. di Biase. “It will be important to see if this index can also distinguish dystonic tremor, which may masquerade as Parkinson’s disease or essential tremor,” he added.
—Erik Greb
Suggested Reading
di Biase L, Brittain JS, Shah SA, et al. Tremor stability index: a new tool for differential diagnosis in tremor syndromes. Brain. 2017 Apr 27 [Epub ahead of print].
Bilateral cellulitis on legs? Think venous stasis dermatitis
SAN FRANCISCO – If a patient presents with bilateral cellulitis on both legs, think venous stasis dermatitis, which is the number one misdiagnosis of cellulitis and a frequent cause of unnecessary hospitalization for so-called “red leg,” according to Kanade Shinkai, MD, PhD.
“It’s easy to make that mistake, because you have a red, hot leg that’s painful, and the patient is having difficulty walking,” Dr. Shinkai said at the UCSF Annual Advances in Internal Medicine meeting. “Venous stasis dermatitis is one of the things you want to learn to recognize, as hospitalization is typically not needed.”
“That has to do with the venous return back to the heart,” said Dr. Shinkai, a dermatologist at UCSF Medical Center. “If it’s unilateral, it’s almost always on the left side.”
Patients often have features of venous insufficiency that cause stasis, including varicose veins and brawny hyperpigmentation on the medial aspects of the ankles. “They have almost no systemic features: no fever, no white count, no lymphadenopathy,” she said. “These patients need some kind of anti-inflammatory medication because the skin is very inflamed. If you happened to take a biopsy, you would see inflammation as well as lymphatic congestion.”
Dr. Shinkai recommends that patients apply a midpotency topical steroid such as triamcinolone to the affected area, followed by compression, ideally antiembolism stockings (TED hose) – but that can be a hard sell.
“When your legs are that swollen, they’re really painful to wear,” she said. “Patients will say, ‘Don’t you come near me with those TED hose.’ If you’re in that situation, tell them to use an Ace wrap with light compression and each day tighten the Ace wrap a little more until they are able to use TED hose with minimal discomfort.”
The differential diagnosis for venous stasis dermatitis includes cellulitis (which rarely presents bilaterally), deep vein thrombosis, asteatotic dermatitis, erysipelas (more superficial cellulitis that results in elevated, shiny plaques), pyomyositis, necrotizing fasciitis, leukocytoclastic vasculitis, and allergic contact dermatitis.
Dr. Shinkai reported having no relevant financial disclosures.
SAN FRANCISCO – If a patient presents with bilateral cellulitis on both legs, think venous stasis dermatitis, which is the number one misdiagnosis of cellulitis and a frequent cause of unnecessary hospitalization for so-called “red leg,” according to Kanade Shinkai, MD, PhD.
“It’s easy to make that mistake, because you have a red, hot leg that’s painful, and the patient is having difficulty walking,” Dr. Shinkai said at the UCSF Annual Advances in Internal Medicine meeting. “Venous stasis dermatitis is one of the things you want to learn to recognize, as hospitalization is typically not needed.”
“That has to do with the venous return back to the heart,” said Dr. Shinkai, a dermatologist at UCSF Medical Center. “If it’s unilateral, it’s almost always on the left side.”
Patients often have features of venous insufficiency that cause stasis, including varicose veins and brawny hyperpigmentation on the medial aspects of the ankles. “They have almost no systemic features: no fever, no white count, no lymphadenopathy,” she said. “These patients need some kind of anti-inflammatory medication because the skin is very inflamed. If you happened to take a biopsy, you would see inflammation as well as lymphatic congestion.”
Dr. Shinkai recommends that patients apply a midpotency topical steroid such as triamcinolone to the affected area, followed by compression, ideally antiembolism stockings (TED hose) – but that can be a hard sell.
“When your legs are that swollen, they’re really painful to wear,” she said. “Patients will say, ‘Don’t you come near me with those TED hose.’ If you’re in that situation, tell them to use an Ace wrap with light compression and each day tighten the Ace wrap a little more until they are able to use TED hose with minimal discomfort.”
The differential diagnosis for venous stasis dermatitis includes cellulitis (which rarely presents bilaterally), deep vein thrombosis, asteatotic dermatitis, erysipelas (more superficial cellulitis that results in elevated, shiny plaques), pyomyositis, necrotizing fasciitis, leukocytoclastic vasculitis, and allergic contact dermatitis.
Dr. Shinkai reported having no relevant financial disclosures.
SAN FRANCISCO – If a patient presents with bilateral cellulitis on both legs, think venous stasis dermatitis, which is the number one misdiagnosis of cellulitis and a frequent cause of unnecessary hospitalization for so-called “red leg,” according to Kanade Shinkai, MD, PhD.
“It’s easy to make that mistake, because you have a red, hot leg that’s painful, and the patient is having difficulty walking,” Dr. Shinkai said at the UCSF Annual Advances in Internal Medicine meeting. “Venous stasis dermatitis is one of the things you want to learn to recognize, as hospitalization is typically not needed.”
“That has to do with the venous return back to the heart,” said Dr. Shinkai, a dermatologist at UCSF Medical Center. “If it’s unilateral, it’s almost always on the left side.”
Patients often have features of venous insufficiency that cause stasis, including varicose veins and brawny hyperpigmentation on the medial aspects of the ankles. “They have almost no systemic features: no fever, no white count, no lymphadenopathy,” she said. “These patients need some kind of anti-inflammatory medication because the skin is very inflamed. If you happened to take a biopsy, you would see inflammation as well as lymphatic congestion.”
Dr. Shinkai recommends that patients apply a midpotency topical steroid such as triamcinolone to the affected area, followed by compression, ideally antiembolism stockings (TED hose) – but that can be a hard sell.
“When your legs are that swollen, they’re really painful to wear,” she said. “Patients will say, ‘Don’t you come near me with those TED hose.’ If you’re in that situation, tell them to use an Ace wrap with light compression and each day tighten the Ace wrap a little more until they are able to use TED hose with minimal discomfort.”
The differential diagnosis for venous stasis dermatitis includes cellulitis (which rarely presents bilaterally), deep vein thrombosis, asteatotic dermatitis, erysipelas (more superficial cellulitis that results in elevated, shiny plaques), pyomyositis, necrotizing fasciitis, leukocytoclastic vasculitis, and allergic contact dermatitis.
Dr. Shinkai reported having no relevant financial disclosures.
AT THE ANNUAL ADVANCES IN INTERNAL MEDICINE
Endo hubris
I began to write this opinion piece on the red-eye flying back from the outstanding Vascular Annual Meeting, recently held in San Diego. I attended breakfast sessions at 6 a.m., as well as presentations and meetings going on well into the evening. I now have bloodshot eyes, tachycardia, and a heightened perception of things.
It is possible that I am just sleep deprived or maybe it’s a result of inhaling the ubiquitous “medical” marijuana vapors that constantly wafted outside the convention center. Whatever the reason, I have returned in a feverish state of excitement that accompanies a sudden significant insight ... that some of us are under the influence, not of some hallucinogenic, but rather an endovascular- induced euphoria whose spell has made us forget that we are still surgeons.
The exhibition hall had the few customary surgical equipment companies with their surgical loupes, vascular clamps, and needle holders. But it was the expansive displays of every type of endovascular tool, guidewires, catheters, x-ray equipment, endografts, and stents, that attracted the crowds. Not a single vascular ultrasound company showed off their duplex scanners despite the fact that vascular surgeons advanced the use of these instruments and made them as omnipresent as they now are in clinical practice. These companies now find it more profitable to show off their wares at cardiology and radiology meetings.
In the lecture hall, audiences packed in to hear the latest method to treat aortic aneurysms with every variety of endovascular device, but there was not a single presentation on open surgical alternatives. Further, an excellent vascular surgery resident was asked how he would handle a pararenal aneurysm in community practice. He admitted that, unless he could be assisted by an experienced surgeon, he would be uncomfortable performing an open surgical repair. Thus, he would be forced to perform an endovascular treatment even if it would not be the best alternative for the patient. But in the future, will there actually be accomplished surgeons who can assist the newly minted vascular surgeon with open procedures? At a breakfast session dedicated to the aging vascular surgeon, we learned that many will soon be retiring since 46% of the Society are now over the age of 50, and 30% are more than 60 years of age.
Where am I going with this? It is apparent my aphorism that a vascular surgeon can “Operate, Medicate, and Dilate” may no longer hold. Perhaps it should now be “Stent, Ablate, Dilate, and Dilate Again.” Future generations of vascular “surgeons” may be no more than cardiologists who don’t treat the heart, able to perform endovascular revascularizations but unable to perform open operations.
Training paradigms may be affected by middle-aged attending surgeons attempting to prove that they are current by adopting endo-treatments rather than open surgery. Some academic surgeons may see the need to experiment with new endo-techniques to advance their careers. Some may see profit patenting new devices. Some may just be enthralled by what Bruce Brenner refers to as “Endo hubris.” Irrespective, dwindling open procedures will inevitably result in inexperienced open surgeons who will feel comfortable only in an endovascular suite.
Payment inequities that undervalue open procedures and overvalue endovascular ones will promote a preference for endovascular alternatives, many of which are less physically demanding than open surgical procedures and bypasses. Thus, the preference for endovascular procedures will be perpetuated.
Concurrently, our cardiology colleagues will be honing their endovascular skills not only in the coronary arteries but also on the periphery. Soon they will claim superiority. Hospital administrators, already under the spell of Cardiology, will notice the declining profit generated by poorly performed open surgery and resultant prolonged hospitalizations. They will then continue to relegate vascular surgeons to even lesser roles than they now have in so-called Heart and Vascular Centers.
As our open skills deteriorate, patients will be forced to travel to the few centers where some exhausted elderly surgeons will perform the occasional open aortic procedure, distal bypass, or, heaven forbid, some ancient procedure referred to as a carotid endarterectomy.
Of course, some may argue that it is time that endovascular procedures replace “barbaric” or disfiguring open procedures. In fact, this may already be the case for the treatment of thoracic aortic pathology. However, I propose that the time for abandoning surgery has not arrived. There are now sufficient data to show that many endo-procedures are no panacea nor are they without significant limitations. Furthermore, if we abandon open surgery we essentially abandon our raison d’etre. What will then distinguish us from interventional radiologists and cardiologists?
I propose it is time for us to embrace our surgical prowess rather than to treat open procedures like Cinderella’s ugly sisters. I would encourage program directors not to stretch indications for use to justify endovascular treatments but rather adopt standard open procedures. If the volume of indicated open procedures is insufficient, then arrange for the trainee to visit another institution.
We must educate referring physicians and hospital administrators about the benefits of well performed open surgery, and we must make sure that such procedures are, in fact, successfully and expeditiously executed. Non-surgeons also need to be informed about some of the drawbacks of endovascular procedures so that they gain a realistic understanding of the pros and cons.
This does not mean being disparaging, but they should be educated about the occurrence and significance of endoleaks, stent fractures, early recurrence, and other complications. Thus informed, they will better understand the rationale for choosing a vascular surgeon to take care of their patients. They will realize that we remain the only specialists devoted to the understanding and treatment of vascular pathology and consequently able to perform the most appropriate and best treatment for that patient.
I am now fully awake. I am convinced that my evaluation of the events at the meeting were not some sleep-deprived or hallucinogenic aberration. I sincerely believe that it is time for drastic adjustments in our thinking about endovascular and open procedures. If not, vascular surgeons and our specialty may become irrelevant and the repercussions for our survival and that of our patients may be devastating. ■
Russell Samson, MD, a physician in the practice of Sarasota Vascular Specialists, Sarasota, Fl., and a clinical professor of surgery, Florida State University, Tallahassee. He is the medical editor of Vascular Specialist.
I began to write this opinion piece on the red-eye flying back from the outstanding Vascular Annual Meeting, recently held in San Diego. I attended breakfast sessions at 6 a.m., as well as presentations and meetings going on well into the evening. I now have bloodshot eyes, tachycardia, and a heightened perception of things.
It is possible that I am just sleep deprived or maybe it’s a result of inhaling the ubiquitous “medical” marijuana vapors that constantly wafted outside the convention center. Whatever the reason, I have returned in a feverish state of excitement that accompanies a sudden significant insight ... that some of us are under the influence, not of some hallucinogenic, but rather an endovascular- induced euphoria whose spell has made us forget that we are still surgeons.
The exhibition hall had the few customary surgical equipment companies with their surgical loupes, vascular clamps, and needle holders. But it was the expansive displays of every type of endovascular tool, guidewires, catheters, x-ray equipment, endografts, and stents, that attracted the crowds. Not a single vascular ultrasound company showed off their duplex scanners despite the fact that vascular surgeons advanced the use of these instruments and made them as omnipresent as they now are in clinical practice. These companies now find it more profitable to show off their wares at cardiology and radiology meetings.
In the lecture hall, audiences packed in to hear the latest method to treat aortic aneurysms with every variety of endovascular device, but there was not a single presentation on open surgical alternatives. Further, an excellent vascular surgery resident was asked how he would handle a pararenal aneurysm in community practice. He admitted that, unless he could be assisted by an experienced surgeon, he would be uncomfortable performing an open surgical repair. Thus, he would be forced to perform an endovascular treatment even if it would not be the best alternative for the patient. But in the future, will there actually be accomplished surgeons who can assist the newly minted vascular surgeon with open procedures? At a breakfast session dedicated to the aging vascular surgeon, we learned that many will soon be retiring since 46% of the Society are now over the age of 50, and 30% are more than 60 years of age.
Where am I going with this? It is apparent my aphorism that a vascular surgeon can “Operate, Medicate, and Dilate” may no longer hold. Perhaps it should now be “Stent, Ablate, Dilate, and Dilate Again.” Future generations of vascular “surgeons” may be no more than cardiologists who don’t treat the heart, able to perform endovascular revascularizations but unable to perform open operations.
Training paradigms may be affected by middle-aged attending surgeons attempting to prove that they are current by adopting endo-treatments rather than open surgery. Some academic surgeons may see the need to experiment with new endo-techniques to advance their careers. Some may see profit patenting new devices. Some may just be enthralled by what Bruce Brenner refers to as “Endo hubris.” Irrespective, dwindling open procedures will inevitably result in inexperienced open surgeons who will feel comfortable only in an endovascular suite.
Payment inequities that undervalue open procedures and overvalue endovascular ones will promote a preference for endovascular alternatives, many of which are less physically demanding than open surgical procedures and bypasses. Thus, the preference for endovascular procedures will be perpetuated.
Concurrently, our cardiology colleagues will be honing their endovascular skills not only in the coronary arteries but also on the periphery. Soon they will claim superiority. Hospital administrators, already under the spell of Cardiology, will notice the declining profit generated by poorly performed open surgery and resultant prolonged hospitalizations. They will then continue to relegate vascular surgeons to even lesser roles than they now have in so-called Heart and Vascular Centers.
As our open skills deteriorate, patients will be forced to travel to the few centers where some exhausted elderly surgeons will perform the occasional open aortic procedure, distal bypass, or, heaven forbid, some ancient procedure referred to as a carotid endarterectomy.
Of course, some may argue that it is time that endovascular procedures replace “barbaric” or disfiguring open procedures. In fact, this may already be the case for the treatment of thoracic aortic pathology. However, I propose that the time for abandoning surgery has not arrived. There are now sufficient data to show that many endo-procedures are no panacea nor are they without significant limitations. Furthermore, if we abandon open surgery we essentially abandon our raison d’etre. What will then distinguish us from interventional radiologists and cardiologists?
I propose it is time for us to embrace our surgical prowess rather than to treat open procedures like Cinderella’s ugly sisters. I would encourage program directors not to stretch indications for use to justify endovascular treatments but rather adopt standard open procedures. If the volume of indicated open procedures is insufficient, then arrange for the trainee to visit another institution.
We must educate referring physicians and hospital administrators about the benefits of well performed open surgery, and we must make sure that such procedures are, in fact, successfully and expeditiously executed. Non-surgeons also need to be informed about some of the drawbacks of endovascular procedures so that they gain a realistic understanding of the pros and cons.
This does not mean being disparaging, but they should be educated about the occurrence and significance of endoleaks, stent fractures, early recurrence, and other complications. Thus informed, they will better understand the rationale for choosing a vascular surgeon to take care of their patients. They will realize that we remain the only specialists devoted to the understanding and treatment of vascular pathology and consequently able to perform the most appropriate and best treatment for that patient.
I am now fully awake. I am convinced that my evaluation of the events at the meeting were not some sleep-deprived or hallucinogenic aberration. I sincerely believe that it is time for drastic adjustments in our thinking about endovascular and open procedures. If not, vascular surgeons and our specialty may become irrelevant and the repercussions for our survival and that of our patients may be devastating. ■
Russell Samson, MD, a physician in the practice of Sarasota Vascular Specialists, Sarasota, Fl., and a clinical professor of surgery, Florida State University, Tallahassee. He is the medical editor of Vascular Specialist.
I began to write this opinion piece on the red-eye flying back from the outstanding Vascular Annual Meeting, recently held in San Diego. I attended breakfast sessions at 6 a.m., as well as presentations and meetings going on well into the evening. I now have bloodshot eyes, tachycardia, and a heightened perception of things.
It is possible that I am just sleep deprived or maybe it’s a result of inhaling the ubiquitous “medical” marijuana vapors that constantly wafted outside the convention center. Whatever the reason, I have returned in a feverish state of excitement that accompanies a sudden significant insight ... that some of us are under the influence, not of some hallucinogenic, but rather an endovascular- induced euphoria whose spell has made us forget that we are still surgeons.
The exhibition hall had the few customary surgical equipment companies with their surgical loupes, vascular clamps, and needle holders. But it was the expansive displays of every type of endovascular tool, guidewires, catheters, x-ray equipment, endografts, and stents, that attracted the crowds. Not a single vascular ultrasound company showed off their duplex scanners despite the fact that vascular surgeons advanced the use of these instruments and made them as omnipresent as they now are in clinical practice. These companies now find it more profitable to show off their wares at cardiology and radiology meetings.
In the lecture hall, audiences packed in to hear the latest method to treat aortic aneurysms with every variety of endovascular device, but there was not a single presentation on open surgical alternatives. Further, an excellent vascular surgery resident was asked how he would handle a pararenal aneurysm in community practice. He admitted that, unless he could be assisted by an experienced surgeon, he would be uncomfortable performing an open surgical repair. Thus, he would be forced to perform an endovascular treatment even if it would not be the best alternative for the patient. But in the future, will there actually be accomplished surgeons who can assist the newly minted vascular surgeon with open procedures? At a breakfast session dedicated to the aging vascular surgeon, we learned that many will soon be retiring since 46% of the Society are now over the age of 50, and 30% are more than 60 years of age.
Where am I going with this? It is apparent my aphorism that a vascular surgeon can “Operate, Medicate, and Dilate” may no longer hold. Perhaps it should now be “Stent, Ablate, Dilate, and Dilate Again.” Future generations of vascular “surgeons” may be no more than cardiologists who don’t treat the heart, able to perform endovascular revascularizations but unable to perform open operations.
Training paradigms may be affected by middle-aged attending surgeons attempting to prove that they are current by adopting endo-treatments rather than open surgery. Some academic surgeons may see the need to experiment with new endo-techniques to advance their careers. Some may see profit patenting new devices. Some may just be enthralled by what Bruce Brenner refers to as “Endo hubris.” Irrespective, dwindling open procedures will inevitably result in inexperienced open surgeons who will feel comfortable only in an endovascular suite.
Payment inequities that undervalue open procedures and overvalue endovascular ones will promote a preference for endovascular alternatives, many of which are less physically demanding than open surgical procedures and bypasses. Thus, the preference for endovascular procedures will be perpetuated.
Concurrently, our cardiology colleagues will be honing their endovascular skills not only in the coronary arteries but also on the periphery. Soon they will claim superiority. Hospital administrators, already under the spell of Cardiology, will notice the declining profit generated by poorly performed open surgery and resultant prolonged hospitalizations. They will then continue to relegate vascular surgeons to even lesser roles than they now have in so-called Heart and Vascular Centers.
As our open skills deteriorate, patients will be forced to travel to the few centers where some exhausted elderly surgeons will perform the occasional open aortic procedure, distal bypass, or, heaven forbid, some ancient procedure referred to as a carotid endarterectomy.
Of course, some may argue that it is time that endovascular procedures replace “barbaric” or disfiguring open procedures. In fact, this may already be the case for the treatment of thoracic aortic pathology. However, I propose that the time for abandoning surgery has not arrived. There are now sufficient data to show that many endo-procedures are no panacea nor are they without significant limitations. Furthermore, if we abandon open surgery we essentially abandon our raison d’etre. What will then distinguish us from interventional radiologists and cardiologists?
I propose it is time for us to embrace our surgical prowess rather than to treat open procedures like Cinderella’s ugly sisters. I would encourage program directors not to stretch indications for use to justify endovascular treatments but rather adopt standard open procedures. If the volume of indicated open procedures is insufficient, then arrange for the trainee to visit another institution.
We must educate referring physicians and hospital administrators about the benefits of well performed open surgery, and we must make sure that such procedures are, in fact, successfully and expeditiously executed. Non-surgeons also need to be informed about some of the drawbacks of endovascular procedures so that they gain a realistic understanding of the pros and cons.
This does not mean being disparaging, but they should be educated about the occurrence and significance of endoleaks, stent fractures, early recurrence, and other complications. Thus informed, they will better understand the rationale for choosing a vascular surgeon to take care of their patients. They will realize that we remain the only specialists devoted to the understanding and treatment of vascular pathology and consequently able to perform the most appropriate and best treatment for that patient.
I am now fully awake. I am convinced that my evaluation of the events at the meeting were not some sleep-deprived or hallucinogenic aberration. I sincerely believe that it is time for drastic adjustments in our thinking about endovascular and open procedures. If not, vascular surgeons and our specialty may become irrelevant and the repercussions for our survival and that of our patients may be devastating. ■
Russell Samson, MD, a physician in the practice of Sarasota Vascular Specialists, Sarasota, Fl., and a clinical professor of surgery, Florida State University, Tallahassee. He is the medical editor of Vascular Specialist.
Cirrhosis Is Linked to an Increased Risk of Stroke
All forms of cirrhosis are associated with an increased risk of stroke, especially hemorrhagic stroke, according to a large, nationally representative cohort study published online ahead of print June 5 in JAMA Neurology.
Cirrhosis is commonly associated with “extrahepatic hemorrhagic and thrombotic processes, such as gastrointestinal bleeding and venous thromboembolism. [But] the cerebrovascular complications of cirrhosis are comparatively less well understood,” said Neal S. Parikh, MD, Resident Physician Neurologist at New York-Presbyterian Hospital in New York City, and colleagues. Previous studies of the association between cirrhosis and stroke have been small and have yielded conflicting results.
To examine the association between cirrhosis and stroke, Dr. Parikh and colleagues conducted a retrospective study that involved 1,618,059 Medicare beneficiaries hospitalized during a six-year period. In all, 15,586 patients (1%) had cirrhosis at baseline, and 77,268 patients developed stroke during a mean of 4.3 years of follow-up. In addition, the overall incidence of stroke was 2.17% per year among patients with cirrhosis, compared with 1.11% per year among patients without cirrhosis. After the data were adjusted to account for stroke risk factors, relevant comorbidities, and demographic traits, the annual incidence of any type of stroke was significantly higher with cirrhosis than without cirrhosis (hazard ratio [HR], 1.4). The association was stronger for intracranial hemorrhage (HR, 1.9) and subarachnoid hemorrhage (HR, 2.4) than for ischemic stroke (HR, 1.3).
The results of several secondary and sensitivity analyses were consistent with those of the primary analysis, regardless of whether the cirrhosis was alcohol-related or the stroke was fatal. The association was strongest among patients who had decompensated cirrhosis and was not evident at all among patients who had mild liver disease, said Dr. Parikh and colleagues.
Although this study was not designed to explore the reasons for an association between cirrhosis and stroke, the investigators noted several possible explanations. First, “cirrhosis is accompanied by a mixed coagulopathy, with potential implications for hemorrhagic and thrombotic processes.” It has been linked to many bleeding complications, including, most recently, cerebral microhemorrhages detectable on brain MRI. In addition, the underlying causes of cirrhosis, including alcohol abuse, hepatitis infection, and metabolic disease, may also contribute to stroke risk.
Alternatively, clinicians caring for patients with cirrhosis “may limit the aggressiveness of stroke prevention”—for example, by limiting antithrombotic medications or statins—because they are mindful of the patient’s increased risk of bleeding and hepatic toxicity, the authors said.
—Mary Ann Moon
Suggested Reading
Parikh NS, Navi BB, Schneider Y, et al. Association between cirrhosis and stroke in a nationally representative cohort. JAMA Neurol. 2017 Jun 5 [Epub ahead of print].
All forms of cirrhosis are associated with an increased risk of stroke, especially hemorrhagic stroke, according to a large, nationally representative cohort study published online ahead of print June 5 in JAMA Neurology.
Cirrhosis is commonly associated with “extrahepatic hemorrhagic and thrombotic processes, such as gastrointestinal bleeding and venous thromboembolism. [But] the cerebrovascular complications of cirrhosis are comparatively less well understood,” said Neal S. Parikh, MD, Resident Physician Neurologist at New York-Presbyterian Hospital in New York City, and colleagues. Previous studies of the association between cirrhosis and stroke have been small and have yielded conflicting results.
To examine the association between cirrhosis and stroke, Dr. Parikh and colleagues conducted a retrospective study that involved 1,618,059 Medicare beneficiaries hospitalized during a six-year period. In all, 15,586 patients (1%) had cirrhosis at baseline, and 77,268 patients developed stroke during a mean of 4.3 years of follow-up. In addition, the overall incidence of stroke was 2.17% per year among patients with cirrhosis, compared with 1.11% per year among patients without cirrhosis. After the data were adjusted to account for stroke risk factors, relevant comorbidities, and demographic traits, the annual incidence of any type of stroke was significantly higher with cirrhosis than without cirrhosis (hazard ratio [HR], 1.4). The association was stronger for intracranial hemorrhage (HR, 1.9) and subarachnoid hemorrhage (HR, 2.4) than for ischemic stroke (HR, 1.3).
The results of several secondary and sensitivity analyses were consistent with those of the primary analysis, regardless of whether the cirrhosis was alcohol-related or the stroke was fatal. The association was strongest among patients who had decompensated cirrhosis and was not evident at all among patients who had mild liver disease, said Dr. Parikh and colleagues.
Although this study was not designed to explore the reasons for an association between cirrhosis and stroke, the investigators noted several possible explanations. First, “cirrhosis is accompanied by a mixed coagulopathy, with potential implications for hemorrhagic and thrombotic processes.” It has been linked to many bleeding complications, including, most recently, cerebral microhemorrhages detectable on brain MRI. In addition, the underlying causes of cirrhosis, including alcohol abuse, hepatitis infection, and metabolic disease, may also contribute to stroke risk.
Alternatively, clinicians caring for patients with cirrhosis “may limit the aggressiveness of stroke prevention”—for example, by limiting antithrombotic medications or statins—because they are mindful of the patient’s increased risk of bleeding and hepatic toxicity, the authors said.
—Mary Ann Moon
Suggested Reading
Parikh NS, Navi BB, Schneider Y, et al. Association between cirrhosis and stroke in a nationally representative cohort. JAMA Neurol. 2017 Jun 5 [Epub ahead of print].
All forms of cirrhosis are associated with an increased risk of stroke, especially hemorrhagic stroke, according to a large, nationally representative cohort study published online ahead of print June 5 in JAMA Neurology.
Cirrhosis is commonly associated with “extrahepatic hemorrhagic and thrombotic processes, such as gastrointestinal bleeding and venous thromboembolism. [But] the cerebrovascular complications of cirrhosis are comparatively less well understood,” said Neal S. Parikh, MD, Resident Physician Neurologist at New York-Presbyterian Hospital in New York City, and colleagues. Previous studies of the association between cirrhosis and stroke have been small and have yielded conflicting results.
To examine the association between cirrhosis and stroke, Dr. Parikh and colleagues conducted a retrospective study that involved 1,618,059 Medicare beneficiaries hospitalized during a six-year period. In all, 15,586 patients (1%) had cirrhosis at baseline, and 77,268 patients developed stroke during a mean of 4.3 years of follow-up. In addition, the overall incidence of stroke was 2.17% per year among patients with cirrhosis, compared with 1.11% per year among patients without cirrhosis. After the data were adjusted to account for stroke risk factors, relevant comorbidities, and demographic traits, the annual incidence of any type of stroke was significantly higher with cirrhosis than without cirrhosis (hazard ratio [HR], 1.4). The association was stronger for intracranial hemorrhage (HR, 1.9) and subarachnoid hemorrhage (HR, 2.4) than for ischemic stroke (HR, 1.3).
The results of several secondary and sensitivity analyses were consistent with those of the primary analysis, regardless of whether the cirrhosis was alcohol-related or the stroke was fatal. The association was strongest among patients who had decompensated cirrhosis and was not evident at all among patients who had mild liver disease, said Dr. Parikh and colleagues.
Although this study was not designed to explore the reasons for an association between cirrhosis and stroke, the investigators noted several possible explanations. First, “cirrhosis is accompanied by a mixed coagulopathy, with potential implications for hemorrhagic and thrombotic processes.” It has been linked to many bleeding complications, including, most recently, cerebral microhemorrhages detectable on brain MRI. In addition, the underlying causes of cirrhosis, including alcohol abuse, hepatitis infection, and metabolic disease, may also contribute to stroke risk.
Alternatively, clinicians caring for patients with cirrhosis “may limit the aggressiveness of stroke prevention”—for example, by limiting antithrombotic medications or statins—because they are mindful of the patient’s increased risk of bleeding and hepatic toxicity, the authors said.
—Mary Ann Moon
Suggested Reading
Parikh NS, Navi BB, Schneider Y, et al. Association between cirrhosis and stroke in a nationally representative cohort. JAMA Neurol. 2017 Jun 5 [Epub ahead of print].
Dr. Turner concludes term as SBAS president teaser
Patricia L. Turner, MD, FACS, Director, American College of Surgeons (ACS) Division of Member Services, recently concluded her term (2016–2017) as president of the Society of Black Academic Surgeons (SBAS). She is the first woman to have served in that role.
Dr. Turner addressed attendees during the April 27–29 SBAS annual meeting, cohosted with the University of Chicago Medicine and Department of Surgery, IL, which is chaired by Jeffrey B. Matthews, MD, FACS, Dallas B. Phemister Professor of Surgery. In her presidential address, The Enduring Influence of Surgical Societies, she described the first time she attended an SBAS meeting as a medical student and expressed her gratitude for being able to lead the meeting as its 22nd president. “I am also grateful to SBAS for the privilege of serving as its first female president,” she said. (Watch a video from the meeting on the Women of SBAS, including Dr. Turner, at www.sbas.net/media/surgeon-spotlight.aspx?id=13).
In her address, Dr. Turner highlighted historical elements of surgery and the activities of surgical societies. She challenged SBAS to continue to expand diversity in all contexts, including age, specialty, gender, and representative institutional members. She urged the organization to extend its influence by amplifying existing relationships with other organizations, such as the ACS, National Institutes of Health, and the Association of American Medical Colleges, while developing new partnerships with other societies and institutions. She also noted that mentorship and excellence in the surgical sciences continue to be the hallmarks of SBAS.
“SBAS has become a formidable scientific forum for surgeons of all backgrounds interested in quality and excellence,” Dr. Turner said. “[Our membership is] small in number, but the power invested in our members and leaders is substantial; we are influential.”
Anthony Stallion, MD, FACS, chief of pediatric surgery, Carolinas HealthCare System, Charlotte, NC, was installed as Dr. Turner’s successor.
Patricia L. Turner, MD, FACS, Director, American College of Surgeons (ACS) Division of Member Services, recently concluded her term (2016–2017) as president of the Society of Black Academic Surgeons (SBAS). She is the first woman to have served in that role.
Dr. Turner addressed attendees during the April 27–29 SBAS annual meeting, cohosted with the University of Chicago Medicine and Department of Surgery, IL, which is chaired by Jeffrey B. Matthews, MD, FACS, Dallas B. Phemister Professor of Surgery. In her presidential address, The Enduring Influence of Surgical Societies, she described the first time she attended an SBAS meeting as a medical student and expressed her gratitude for being able to lead the meeting as its 22nd president. “I am also grateful to SBAS for the privilege of serving as its first female president,” she said. (Watch a video from the meeting on the Women of SBAS, including Dr. Turner, at www.sbas.net/media/surgeon-spotlight.aspx?id=13).
In her address, Dr. Turner highlighted historical elements of surgery and the activities of surgical societies. She challenged SBAS to continue to expand diversity in all contexts, including age, specialty, gender, and representative institutional members. She urged the organization to extend its influence by amplifying existing relationships with other organizations, such as the ACS, National Institutes of Health, and the Association of American Medical Colleges, while developing new partnerships with other societies and institutions. She also noted that mentorship and excellence in the surgical sciences continue to be the hallmarks of SBAS.
“SBAS has become a formidable scientific forum for surgeons of all backgrounds interested in quality and excellence,” Dr. Turner said. “[Our membership is] small in number, but the power invested in our members and leaders is substantial; we are influential.”
Anthony Stallion, MD, FACS, chief of pediatric surgery, Carolinas HealthCare System, Charlotte, NC, was installed as Dr. Turner’s successor.
Patricia L. Turner, MD, FACS, Director, American College of Surgeons (ACS) Division of Member Services, recently concluded her term (2016–2017) as president of the Society of Black Academic Surgeons (SBAS). She is the first woman to have served in that role.
Dr. Turner addressed attendees during the April 27–29 SBAS annual meeting, cohosted with the University of Chicago Medicine and Department of Surgery, IL, which is chaired by Jeffrey B. Matthews, MD, FACS, Dallas B. Phemister Professor of Surgery. In her presidential address, The Enduring Influence of Surgical Societies, she described the first time she attended an SBAS meeting as a medical student and expressed her gratitude for being able to lead the meeting as its 22nd president. “I am also grateful to SBAS for the privilege of serving as its first female president,” she said. (Watch a video from the meeting on the Women of SBAS, including Dr. Turner, at www.sbas.net/media/surgeon-spotlight.aspx?id=13).
In her address, Dr. Turner highlighted historical elements of surgery and the activities of surgical societies. She challenged SBAS to continue to expand diversity in all contexts, including age, specialty, gender, and representative institutional members. She urged the organization to extend its influence by amplifying existing relationships with other organizations, such as the ACS, National Institutes of Health, and the Association of American Medical Colleges, while developing new partnerships with other societies and institutions. She also noted that mentorship and excellence in the surgical sciences continue to be the hallmarks of SBAS.
“SBAS has become a formidable scientific forum for surgeons of all backgrounds interested in quality and excellence,” Dr. Turner said. “[Our membership is] small in number, but the power invested in our members and leaders is substantial; we are influential.”
Anthony Stallion, MD, FACS, chief of pediatric surgery, Carolinas HealthCare System, Charlotte, NC, was installed as Dr. Turner’s successor.
NSAIDs remain a concern in colorectal ERAS protocols
SEATTLE – Nonselective NSAIDs increase the risk of anastomotic leaks after colorectal surgery, according to a meta-analysis from the University of Sydney, Australia.
After combing results from six randomized, controlled trials and seven retrospective studies involving a total of 23,508 patients, investigators found that postop nonselective NSAIDs (odds ratio, 0.54; 95% CI, 0.43-0.67; P less than .00001), and especially diclofenac (OR, 0.39; 95% CI, 0.28-0.55; P less than .00001), were both associated with an increased risk of leakage.
There was an increased risk with all NSAIDs compared to patients who did not receive them after surgery, but the risk was statistically significant only for nonselective options like diclofenac on subgroup analysis. There was a trend for increased leakage with the nonselective agent ketorolac, as well, but it was not significant (OR, 0.71; 95% CI, 0.35-1.43; P = .34).
“I’m not going to say we need to wait for more studies; there’s something here. We have to be aware there could be a high risk of leakage with nonsteroidals, and we have to be mindful of that with our ERAS [Enhanced Recovery after Surgery] protocols. I don’t think you should be using nonsteroidals unless you are using them in a trial” and collecting data, “because of the uncertainty,” lead investigator and colorectal surgeon Christopher Young, MD, a clinical associate professor of surgery at the University of Sydney, said at the American Society of Colon and Rectal Surgeons annual meeting.
NSAIDS are a routine part of colorectal ERAS protocols in some places to limit opioid use and hasten recovery and hospital discharge, but there’s been concern for some time that they might also increase the risk of anastomotic leakage. The new Australian findings fit in with previous investigations that raised concerns.
A 2016 review, for instance, found that among 856 patients undergoing an elective colon or rectal resection for cancer, the anastomotic leakage rate was significantly higher in the group that received nonsteroidal anti-inflammatory drugs compared to patients who did not (9.2% versus 5.3%). The higher rate was only seen in patients receiving diclofenac. “The use of diclofenac in colorectal surgery can no longer be recommended. Alternatives for postoperative analgesia need to be explored within an enhanced recovery program,” the investigators concluded (J Gastrointest Surg. 2016 Apr;20[4]:776-82. doi: 10.1007/s11605-015-3010-1).
A review of 13,082 bariatric and colorectal surgery patients in Washington State found that NSAIDs beginning within 24 hours after surgery were associated with a 70% increased risk of anastomotic leaks in nonelective colorectal surgery, with a leak rate of 12.3% in the NSAID group and 8.3% in the non-NSAID group (OR, 1.70; 95% CI, 1.11–2.68; P = .01). Although it was unclear which nonsteroidals patients received, intravenous ketorolac or ibuprofen were likely the most common (JAMA Surg. 2015 Mar 1;150[3]: 223–8).
It’s unknown why, exactly, NSAIDs impair healing and anastomotic strength, but it’s thought to be related to effects on prostaglandin synthesis, Dr. Young noted.
Dr. Young had no disclosures.
SEATTLE – Nonselective NSAIDs increase the risk of anastomotic leaks after colorectal surgery, according to a meta-analysis from the University of Sydney, Australia.
After combing results from six randomized, controlled trials and seven retrospective studies involving a total of 23,508 patients, investigators found that postop nonselective NSAIDs (odds ratio, 0.54; 95% CI, 0.43-0.67; P less than .00001), and especially diclofenac (OR, 0.39; 95% CI, 0.28-0.55; P less than .00001), were both associated with an increased risk of leakage.
There was an increased risk with all NSAIDs compared to patients who did not receive them after surgery, but the risk was statistically significant only for nonselective options like diclofenac on subgroup analysis. There was a trend for increased leakage with the nonselective agent ketorolac, as well, but it was not significant (OR, 0.71; 95% CI, 0.35-1.43; P = .34).
“I’m not going to say we need to wait for more studies; there’s something here. We have to be aware there could be a high risk of leakage with nonsteroidals, and we have to be mindful of that with our ERAS [Enhanced Recovery after Surgery] protocols. I don’t think you should be using nonsteroidals unless you are using them in a trial” and collecting data, “because of the uncertainty,” lead investigator and colorectal surgeon Christopher Young, MD, a clinical associate professor of surgery at the University of Sydney, said at the American Society of Colon and Rectal Surgeons annual meeting.
NSAIDS are a routine part of colorectal ERAS protocols in some places to limit opioid use and hasten recovery and hospital discharge, but there’s been concern for some time that they might also increase the risk of anastomotic leakage. The new Australian findings fit in with previous investigations that raised concerns.
A 2016 review, for instance, found that among 856 patients undergoing an elective colon or rectal resection for cancer, the anastomotic leakage rate was significantly higher in the group that received nonsteroidal anti-inflammatory drugs compared to patients who did not (9.2% versus 5.3%). The higher rate was only seen in patients receiving diclofenac. “The use of diclofenac in colorectal surgery can no longer be recommended. Alternatives for postoperative analgesia need to be explored within an enhanced recovery program,” the investigators concluded (J Gastrointest Surg. 2016 Apr;20[4]:776-82. doi: 10.1007/s11605-015-3010-1).
A review of 13,082 bariatric and colorectal surgery patients in Washington State found that NSAIDs beginning within 24 hours after surgery were associated with a 70% increased risk of anastomotic leaks in nonelective colorectal surgery, with a leak rate of 12.3% in the NSAID group and 8.3% in the non-NSAID group (OR, 1.70; 95% CI, 1.11–2.68; P = .01). Although it was unclear which nonsteroidals patients received, intravenous ketorolac or ibuprofen were likely the most common (JAMA Surg. 2015 Mar 1;150[3]: 223–8).
It’s unknown why, exactly, NSAIDs impair healing and anastomotic strength, but it’s thought to be related to effects on prostaglandin synthesis, Dr. Young noted.
Dr. Young had no disclosures.
SEATTLE – Nonselective NSAIDs increase the risk of anastomotic leaks after colorectal surgery, according to a meta-analysis from the University of Sydney, Australia.
After combing results from six randomized, controlled trials and seven retrospective studies involving a total of 23,508 patients, investigators found that postop nonselective NSAIDs (odds ratio, 0.54; 95% CI, 0.43-0.67; P less than .00001), and especially diclofenac (OR, 0.39; 95% CI, 0.28-0.55; P less than .00001), were both associated with an increased risk of leakage.
There was an increased risk with all NSAIDs compared to patients who did not receive them after surgery, but the risk was statistically significant only for nonselective options like diclofenac on subgroup analysis. There was a trend for increased leakage with the nonselective agent ketorolac, as well, but it was not significant (OR, 0.71; 95% CI, 0.35-1.43; P = .34).
“I’m not going to say we need to wait for more studies; there’s something here. We have to be aware there could be a high risk of leakage with nonsteroidals, and we have to be mindful of that with our ERAS [Enhanced Recovery after Surgery] protocols. I don’t think you should be using nonsteroidals unless you are using them in a trial” and collecting data, “because of the uncertainty,” lead investigator and colorectal surgeon Christopher Young, MD, a clinical associate professor of surgery at the University of Sydney, said at the American Society of Colon and Rectal Surgeons annual meeting.
NSAIDS are a routine part of colorectal ERAS protocols in some places to limit opioid use and hasten recovery and hospital discharge, but there’s been concern for some time that they might also increase the risk of anastomotic leakage. The new Australian findings fit in with previous investigations that raised concerns.
A 2016 review, for instance, found that among 856 patients undergoing an elective colon or rectal resection for cancer, the anastomotic leakage rate was significantly higher in the group that received nonsteroidal anti-inflammatory drugs compared to patients who did not (9.2% versus 5.3%). The higher rate was only seen in patients receiving diclofenac. “The use of diclofenac in colorectal surgery can no longer be recommended. Alternatives for postoperative analgesia need to be explored within an enhanced recovery program,” the investigators concluded (J Gastrointest Surg. 2016 Apr;20[4]:776-82. doi: 10.1007/s11605-015-3010-1).
A review of 13,082 bariatric and colorectal surgery patients in Washington State found that NSAIDs beginning within 24 hours after surgery were associated with a 70% increased risk of anastomotic leaks in nonelective colorectal surgery, with a leak rate of 12.3% in the NSAID group and 8.3% in the non-NSAID group (OR, 1.70; 95% CI, 1.11–2.68; P = .01). Although it was unclear which nonsteroidals patients received, intravenous ketorolac or ibuprofen were likely the most common (JAMA Surg. 2015 Mar 1;150[3]: 223–8).
It’s unknown why, exactly, NSAIDs impair healing and anastomotic strength, but it’s thought to be related to effects on prostaglandin synthesis, Dr. Young noted.
Dr. Young had no disclosures.
AT ASCRS 2017
Key clinical point:
Major finding: Postop nonselective NSAIDs (OR, 0.54; 95% CI, 0.43-0.67; P less than .00001), and especially diclofenac (OR, 0.39; 95% CI, 0.28-0.55; P less than .00001), were both associated with an increased risk of leakage.
Data source: Meta-analysis involving 23,508 patients
Disclosures: The presenter had no disclosures.
Study shows that 20% of inpatients given antibiotics develop adverse reactions
Twenty percent of hospitalized adults given antibiotics develop adverse drug events, including GI, nephrotoxic, hematologic, cardiac, and neurotoxic effects, according to a report in JAMA Internal Medicine.
This high frequency of adverse reactions “may not be recognized by clinicians because [these events] have varied manifestations, clinicians may be unaware of the risks associated with specific antibiotic agents, or because they occur after patients are discharged from the hospital,” said Pranita D. Tamma, MD, of the division of pediatric infectious diseases, Johns Hopkins University, Baltimore, and her associates.
They assessed antibiotic-associated adverse drug events in all 1,488 adults admitted to four general medicine services at a single medical center during a 9-month period and given at least 24 hours of any antibiotic therapy. The most common indications for antibiotics were urinary tract infections (12%), skin and soft-tissue infections (8%), and community-acquired pneumonia (7%).
Perhaps as important, the researchers noted, 19% of these adverse drug events were attributed to unnecessary antibiotics – drugs given for conditions for which they were not clinically indicated according to the hospital’s own antibiotic guidelines. These included asymptomatic bacteriuria, aspiration pneumonitis, and heart failure (JAMA Intern. Med. 2017 June 12. doi: 10.1001/jamainternmed.2017.1938).
The most common adverse reactions that developed within 30 days were GI, renal, and hematologic abnormalities. Neurotoxic effects included encephalopathy and seizures; cardiotoxic effects included QTc prolongation. Less frequent adverse events included anaphylaxis, daptomycin-associated myositis, trimethoprim/sulfamethoxazole-associated pancreatitis, linezolid-associated neuropathy, and ciprofloxacin-related tendinitis. The most common adverse reactions that developed within 90 days were C. difficile infections and infections involving multidrug-resistant organisms.
“Our findings underscore the importance of avoiding unnecessary antibiotic prescribing to reduce the harm that can result from antibiotic-associated adverse drug events,” Dr. Tamma and her associates said.
Twenty percent of hospitalized adults given antibiotics develop adverse drug events, including GI, nephrotoxic, hematologic, cardiac, and neurotoxic effects, according to a report in JAMA Internal Medicine.
This high frequency of adverse reactions “may not be recognized by clinicians because [these events] have varied manifestations, clinicians may be unaware of the risks associated with specific antibiotic agents, or because they occur after patients are discharged from the hospital,” said Pranita D. Tamma, MD, of the division of pediatric infectious diseases, Johns Hopkins University, Baltimore, and her associates.
They assessed antibiotic-associated adverse drug events in all 1,488 adults admitted to four general medicine services at a single medical center during a 9-month period and given at least 24 hours of any antibiotic therapy. The most common indications for antibiotics were urinary tract infections (12%), skin and soft-tissue infections (8%), and community-acquired pneumonia (7%).
Perhaps as important, the researchers noted, 19% of these adverse drug events were attributed to unnecessary antibiotics – drugs given for conditions for which they were not clinically indicated according to the hospital’s own antibiotic guidelines. These included asymptomatic bacteriuria, aspiration pneumonitis, and heart failure (JAMA Intern. Med. 2017 June 12. doi: 10.1001/jamainternmed.2017.1938).
The most common adverse reactions that developed within 30 days were GI, renal, and hematologic abnormalities. Neurotoxic effects included encephalopathy and seizures; cardiotoxic effects included QTc prolongation. Less frequent adverse events included anaphylaxis, daptomycin-associated myositis, trimethoprim/sulfamethoxazole-associated pancreatitis, linezolid-associated neuropathy, and ciprofloxacin-related tendinitis. The most common adverse reactions that developed within 90 days were C. difficile infections and infections involving multidrug-resistant organisms.
“Our findings underscore the importance of avoiding unnecessary antibiotic prescribing to reduce the harm that can result from antibiotic-associated adverse drug events,” Dr. Tamma and her associates said.
Twenty percent of hospitalized adults given antibiotics develop adverse drug events, including GI, nephrotoxic, hematologic, cardiac, and neurotoxic effects, according to a report in JAMA Internal Medicine.
This high frequency of adverse reactions “may not be recognized by clinicians because [these events] have varied manifestations, clinicians may be unaware of the risks associated with specific antibiotic agents, or because they occur after patients are discharged from the hospital,” said Pranita D. Tamma, MD, of the division of pediatric infectious diseases, Johns Hopkins University, Baltimore, and her associates.
They assessed antibiotic-associated adverse drug events in all 1,488 adults admitted to four general medicine services at a single medical center during a 9-month period and given at least 24 hours of any antibiotic therapy. The most common indications for antibiotics were urinary tract infections (12%), skin and soft-tissue infections (8%), and community-acquired pneumonia (7%).
Perhaps as important, the researchers noted, 19% of these adverse drug events were attributed to unnecessary antibiotics – drugs given for conditions for which they were not clinically indicated according to the hospital’s own antibiotic guidelines. These included asymptomatic bacteriuria, aspiration pneumonitis, and heart failure (JAMA Intern. Med. 2017 June 12. doi: 10.1001/jamainternmed.2017.1938).
The most common adverse reactions that developed within 30 days were GI, renal, and hematologic abnormalities. Neurotoxic effects included encephalopathy and seizures; cardiotoxic effects included QTc prolongation. Less frequent adverse events included anaphylaxis, daptomycin-associated myositis, trimethoprim/sulfamethoxazole-associated pancreatitis, linezolid-associated neuropathy, and ciprofloxacin-related tendinitis. The most common adverse reactions that developed within 90 days were C. difficile infections and infections involving multidrug-resistant organisms.
“Our findings underscore the importance of avoiding unnecessary antibiotic prescribing to reduce the harm that can result from antibiotic-associated adverse drug events,” Dr. Tamma and her associates said.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Among hospitalized adults given antibiotics, 20% develop adverse reactions, including GI, nephrotoxic, hematologic, cardiac, and neurotoxic effects.
Major finding: Among 1,488 patients, 298 (20%) developed 324 adverse reactions to antibiotics – 73% during hospitalization and 27% after discharge – requiring prolonged hospitalization; a subsequent hospitalization; an ED visit; or additional lab tests, ECGs, or imaging studies.
Data source: A single-center retrospective cohort study involving all 1,488 general medicine inpatients admitted during a 9-month period who received any antibiotic for at least 24 hours.
Disclosures: This study was supported by Pfizer Independent Grants for Learning and Change and the Joint Commission. Dr. Tamma and her associates reported having no relevant financial disclosures.