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Fecal microbiota transplant shows promise for hepatic encephalopathy
VIENNA –
The oral fecal microbiota transplant (FMT), modeled on guideline-directed treatment for Clostridium difficile (Clin Infect Dis. 2018 April 1;66[7]:e1-48), was linked with a cut in hospitalizations and serious adverse events, as well as a clinically meaningful improvement in a cognitive measure specific for hepatic encephalopathy, Jasmohan S. Bajaj, MD, said at the meeting sponsored by the European Association for the Study of the Liver. Given the preliminary scope of the study, the next step is to assess the treatment in more patients and to evaluate delivery of the FMT specifically to the upper or lower gastrointestinal tract, said Dr. Bajaj, a hepatologist at Virginia Commonwealth University and McGuire VA Medical Center, both in Richmond.
The study included 20 patients with recurrent hepatic encephalopathy (RHE) and a history of at least two encephalopathy episodes despite treatment with lactulose and rifaximin (Xifaxan). After a baseline assessment, 10 patients received a single, oral dose of FMT contained in 15 capsules and composed of fecal material from the OpenBiome collection, and 10 patients received placebo capsules. All of the FMT material came from a single donor and contained a high level of beneficial microbial types, specifically Lachnospiraceae and Ruminococcaceae species. Patients averaged 64 years of age.
During 5 months of follow-up, 6 of the 10 placebo patients had a serious adverse event versus 1 of the 10 patients treated with an active FMT; altogether, there were 11 serious adverse events among the placebo patients versus only 1 event among the FMT patients, Dr. Bajaj reported. Three patients in the control arm had a total of seven hepatic encephalopathy events, compared with a single patient with one event in the intervention arm.
Enrolled patients also underwent two cognitive tests at baseline and during follow-up. Using a Stroop smartphone app (EncephalApp) designed to assess patients with RHE (Hepatology. 2013 Sept;58[3]:1122-32), the researchers found an average 51-second improvement in OffTime+OnTime, a statistically significant and clinically meaningful improvement in the patients treated with FMT, whereas the control patients showed no statistically significant change in this parameter. The second cognitive measure was the average performance by patients using the Psychometric Hepatic Encephalopathy Score (Curr Gastroenterol Rep. 2014 Jan;16[1]:362), which showed no significant change after treatment in either study arm. The actively treated patients also showed favorable changes in the microbial composition of their stool and mucosa, as well as an enhanced small intestinal barrier, following treatment, Dr. Bajaj said.
SOURCE: Bajaj JS et al. J Hepatol. 2019 April;70[1]:e55.
VIENNA –
The oral fecal microbiota transplant (FMT), modeled on guideline-directed treatment for Clostridium difficile (Clin Infect Dis. 2018 April 1;66[7]:e1-48), was linked with a cut in hospitalizations and serious adverse events, as well as a clinically meaningful improvement in a cognitive measure specific for hepatic encephalopathy, Jasmohan S. Bajaj, MD, said at the meeting sponsored by the European Association for the Study of the Liver. Given the preliminary scope of the study, the next step is to assess the treatment in more patients and to evaluate delivery of the FMT specifically to the upper or lower gastrointestinal tract, said Dr. Bajaj, a hepatologist at Virginia Commonwealth University and McGuire VA Medical Center, both in Richmond.
The study included 20 patients with recurrent hepatic encephalopathy (RHE) and a history of at least two encephalopathy episodes despite treatment with lactulose and rifaximin (Xifaxan). After a baseline assessment, 10 patients received a single, oral dose of FMT contained in 15 capsules and composed of fecal material from the OpenBiome collection, and 10 patients received placebo capsules. All of the FMT material came from a single donor and contained a high level of beneficial microbial types, specifically Lachnospiraceae and Ruminococcaceae species. Patients averaged 64 years of age.
During 5 months of follow-up, 6 of the 10 placebo patients had a serious adverse event versus 1 of the 10 patients treated with an active FMT; altogether, there were 11 serious adverse events among the placebo patients versus only 1 event among the FMT patients, Dr. Bajaj reported. Three patients in the control arm had a total of seven hepatic encephalopathy events, compared with a single patient with one event in the intervention arm.
Enrolled patients also underwent two cognitive tests at baseline and during follow-up. Using a Stroop smartphone app (EncephalApp) designed to assess patients with RHE (Hepatology. 2013 Sept;58[3]:1122-32), the researchers found an average 51-second improvement in OffTime+OnTime, a statistically significant and clinically meaningful improvement in the patients treated with FMT, whereas the control patients showed no statistically significant change in this parameter. The second cognitive measure was the average performance by patients using the Psychometric Hepatic Encephalopathy Score (Curr Gastroenterol Rep. 2014 Jan;16[1]:362), which showed no significant change after treatment in either study arm. The actively treated patients also showed favorable changes in the microbial composition of their stool and mucosa, as well as an enhanced small intestinal barrier, following treatment, Dr. Bajaj said.
SOURCE: Bajaj JS et al. J Hepatol. 2019 April;70[1]:e55.
VIENNA –
The oral fecal microbiota transplant (FMT), modeled on guideline-directed treatment for Clostridium difficile (Clin Infect Dis. 2018 April 1;66[7]:e1-48), was linked with a cut in hospitalizations and serious adverse events, as well as a clinically meaningful improvement in a cognitive measure specific for hepatic encephalopathy, Jasmohan S. Bajaj, MD, said at the meeting sponsored by the European Association for the Study of the Liver. Given the preliminary scope of the study, the next step is to assess the treatment in more patients and to evaluate delivery of the FMT specifically to the upper or lower gastrointestinal tract, said Dr. Bajaj, a hepatologist at Virginia Commonwealth University and McGuire VA Medical Center, both in Richmond.
The study included 20 patients with recurrent hepatic encephalopathy (RHE) and a history of at least two encephalopathy episodes despite treatment with lactulose and rifaximin (Xifaxan). After a baseline assessment, 10 patients received a single, oral dose of FMT contained in 15 capsules and composed of fecal material from the OpenBiome collection, and 10 patients received placebo capsules. All of the FMT material came from a single donor and contained a high level of beneficial microbial types, specifically Lachnospiraceae and Ruminococcaceae species. Patients averaged 64 years of age.
During 5 months of follow-up, 6 of the 10 placebo patients had a serious adverse event versus 1 of the 10 patients treated with an active FMT; altogether, there were 11 serious adverse events among the placebo patients versus only 1 event among the FMT patients, Dr. Bajaj reported. Three patients in the control arm had a total of seven hepatic encephalopathy events, compared with a single patient with one event in the intervention arm.
Enrolled patients also underwent two cognitive tests at baseline and during follow-up. Using a Stroop smartphone app (EncephalApp) designed to assess patients with RHE (Hepatology. 2013 Sept;58[3]:1122-32), the researchers found an average 51-second improvement in OffTime+OnTime, a statistically significant and clinically meaningful improvement in the patients treated with FMT, whereas the control patients showed no statistically significant change in this parameter. The second cognitive measure was the average performance by patients using the Psychometric Hepatic Encephalopathy Score (Curr Gastroenterol Rep. 2014 Jan;16[1]:362), which showed no significant change after treatment in either study arm. The actively treated patients also showed favorable changes in the microbial composition of their stool and mucosa, as well as an enhanced small intestinal barrier, following treatment, Dr. Bajaj said.
SOURCE: Bajaj JS et al. J Hepatol. 2019 April;70[1]:e55.
REPORTING FROM ILC 2019
Vaginal brachytherapy more toxic than pelvic RT in endometrial carcinoma
, according to results from a phase 3 trial.
The GOG-0249 study comprised 601 patients with high-intermediate– and high-risk early-stage endometrial carcinoma who were randomized in a 1:1 fashion to receive vaginal cuff brachytherapy plus paclitaxel and carboplatin or pelvic RT every 21 days for a total of three cycles.
Those in the brachytherapy group received treatment at both high and low-dosing rates. Paclitaxel was given at a dose of 175 mg/m2 infused over 3 hours, succeeded by carboplatin (area under the curve, 6) infused over 45 minutes. Pelvic RT was provided at a dose of 45 to 50.4 Gy over a period of 5-6 weeks.
“The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy increases recurrence-free survival (RFS) compared with pelvic RT,” wrote Marcus E. Randall, MD, of the University of Kentucky, Lexington, and colleagues. The report is in the Journal of Clinical Oncology.
Additional outcomes measured were overall survival and acute toxicity.
After analysis, the researchers found that vaginal brachytherapy plus chemotherapy did not show superiority over pelvic RT in terms of 60-month RFS (hazard ratio, 0.92; 90% confidence limit, 0.69-1.23). Also, there was no significant difference for overall survival (HR, 1.04; 90% confidence limit, 0.71-1.52).
With respect to safety, acute adverse events were more common and severe in the vaginal brachytherapy plus chemotherapy group. However, “differences in late toxicity were minimal,” Dr. Randall and colleagues reported.
“Pelvic RT remains an appropriate treatment for high-risk early-stage endometrial carcinoma,” they wrote. “Novel combinations, dose intensification, and additional translational research represent potential paths forward.”
The study was supported by grant funding from the National Cancer Institute and the Memorial Sloan Kettering Cancer Center. The authors reported financial affiliations with AstraZeneca, Genentech, Genmab, Janssen, Johnson & Johnson, Tesaro, and several others.
SOURCE: Randall ME et al. J Clin Oncol. 2019 Apr 17. doi: 10.1200/JCO.18.01575.
, according to results from a phase 3 trial.
The GOG-0249 study comprised 601 patients with high-intermediate– and high-risk early-stage endometrial carcinoma who were randomized in a 1:1 fashion to receive vaginal cuff brachytherapy plus paclitaxel and carboplatin or pelvic RT every 21 days for a total of three cycles.
Those in the brachytherapy group received treatment at both high and low-dosing rates. Paclitaxel was given at a dose of 175 mg/m2 infused over 3 hours, succeeded by carboplatin (area under the curve, 6) infused over 45 minutes. Pelvic RT was provided at a dose of 45 to 50.4 Gy over a period of 5-6 weeks.
“The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy increases recurrence-free survival (RFS) compared with pelvic RT,” wrote Marcus E. Randall, MD, of the University of Kentucky, Lexington, and colleagues. The report is in the Journal of Clinical Oncology.
Additional outcomes measured were overall survival and acute toxicity.
After analysis, the researchers found that vaginal brachytherapy plus chemotherapy did not show superiority over pelvic RT in terms of 60-month RFS (hazard ratio, 0.92; 90% confidence limit, 0.69-1.23). Also, there was no significant difference for overall survival (HR, 1.04; 90% confidence limit, 0.71-1.52).
With respect to safety, acute adverse events were more common and severe in the vaginal brachytherapy plus chemotherapy group. However, “differences in late toxicity were minimal,” Dr. Randall and colleagues reported.
“Pelvic RT remains an appropriate treatment for high-risk early-stage endometrial carcinoma,” they wrote. “Novel combinations, dose intensification, and additional translational research represent potential paths forward.”
The study was supported by grant funding from the National Cancer Institute and the Memorial Sloan Kettering Cancer Center. The authors reported financial affiliations with AstraZeneca, Genentech, Genmab, Janssen, Johnson & Johnson, Tesaro, and several others.
SOURCE: Randall ME et al. J Clin Oncol. 2019 Apr 17. doi: 10.1200/JCO.18.01575.
, according to results from a phase 3 trial.
The GOG-0249 study comprised 601 patients with high-intermediate– and high-risk early-stage endometrial carcinoma who were randomized in a 1:1 fashion to receive vaginal cuff brachytherapy plus paclitaxel and carboplatin or pelvic RT every 21 days for a total of three cycles.
Those in the brachytherapy group received treatment at both high and low-dosing rates. Paclitaxel was given at a dose of 175 mg/m2 infused over 3 hours, succeeded by carboplatin (area under the curve, 6) infused over 45 minutes. Pelvic RT was provided at a dose of 45 to 50.4 Gy over a period of 5-6 weeks.
“The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy increases recurrence-free survival (RFS) compared with pelvic RT,” wrote Marcus E. Randall, MD, of the University of Kentucky, Lexington, and colleagues. The report is in the Journal of Clinical Oncology.
Additional outcomes measured were overall survival and acute toxicity.
After analysis, the researchers found that vaginal brachytherapy plus chemotherapy did not show superiority over pelvic RT in terms of 60-month RFS (hazard ratio, 0.92; 90% confidence limit, 0.69-1.23). Also, there was no significant difference for overall survival (HR, 1.04; 90% confidence limit, 0.71-1.52).
With respect to safety, acute adverse events were more common and severe in the vaginal brachytherapy plus chemotherapy group. However, “differences in late toxicity were minimal,” Dr. Randall and colleagues reported.
“Pelvic RT remains an appropriate treatment for high-risk early-stage endometrial carcinoma,” they wrote. “Novel combinations, dose intensification, and additional translational research represent potential paths forward.”
The study was supported by grant funding from the National Cancer Institute and the Memorial Sloan Kettering Cancer Center. The authors reported financial affiliations with AstraZeneca, Genentech, Genmab, Janssen, Johnson & Johnson, Tesaro, and several others.
SOURCE: Randall ME et al. J Clin Oncol. 2019 Apr 17. doi: 10.1200/JCO.18.01575.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Damage of the Lateral Geniculate Nucleus in MS
Key clinical point: Lateral geniculate nucleus (LGN) volume loss in multiple sclerosis (MS) indicates structural damage with potential functional relevance.
Major finding: LGN volume was reduced in patients with relapsing-remitting MS vs healthy controls and was associated with ganglion cell-inner plexiform layer (GC-IPL) thickness and correlated with optic radiation (OR) lesion volume.
Study details: A cross-sectional study of 34 patients with relapsing-remitting MS and 33 matched healthy controls.
Disclosures: The lead author received funding for speaker or travel honoraria from Sanofi-Genzyme, Bayer AG, Teva, UCB-Pharma AG, and Hoffmann-La Roche.
Citation: Papadopoulou, et al. Neurology. doi:10.1212/WNL.0000000000007450.
Key clinical point: Lateral geniculate nucleus (LGN) volume loss in multiple sclerosis (MS) indicates structural damage with potential functional relevance.
Major finding: LGN volume was reduced in patients with relapsing-remitting MS vs healthy controls and was associated with ganglion cell-inner plexiform layer (GC-IPL) thickness and correlated with optic radiation (OR) lesion volume.
Study details: A cross-sectional study of 34 patients with relapsing-remitting MS and 33 matched healthy controls.
Disclosures: The lead author received funding for speaker or travel honoraria from Sanofi-Genzyme, Bayer AG, Teva, UCB-Pharma AG, and Hoffmann-La Roche.
Citation: Papadopoulou, et al. Neurology. doi:10.1212/WNL.0000000000007450.
Key clinical point: Lateral geniculate nucleus (LGN) volume loss in multiple sclerosis (MS) indicates structural damage with potential functional relevance.
Major finding: LGN volume was reduced in patients with relapsing-remitting MS vs healthy controls and was associated with ganglion cell-inner plexiform layer (GC-IPL) thickness and correlated with optic radiation (OR) lesion volume.
Study details: A cross-sectional study of 34 patients with relapsing-remitting MS and 33 matched healthy controls.
Disclosures: The lead author received funding for speaker or travel honoraria from Sanofi-Genzyme, Bayer AG, Teva, UCB-Pharma AG, and Hoffmann-La Roche.
Citation: Papadopoulou, et al. Neurology. doi:10.1212/WNL.0000000000007450.
Survey of MS Patients Reveals Pregnancy-Related Concerns
Key clinical point: Patients with multiple sclerosis report a wide range of concerns about family planning and pregnancy.
Major finding: Of the 137 respondents who did not become pregnant following diagnosis, 22 (16%) indicated that their decision was driven by multiple sclerosis–related concerns, including MS worsening with pregnancy (64%).
Study details: A survey of 174 women with confirmed MS diagnosis who received care at the University of Virginia Medical Center.
Disclosures: The study was supported by the ziMS Foundation.
Citation: Engel CE et al. ACTRIMS Forum 2019, Poster 307.
Key clinical point: Patients with multiple sclerosis report a wide range of concerns about family planning and pregnancy.
Major finding: Of the 137 respondents who did not become pregnant following diagnosis, 22 (16%) indicated that their decision was driven by multiple sclerosis–related concerns, including MS worsening with pregnancy (64%).
Study details: A survey of 174 women with confirmed MS diagnosis who received care at the University of Virginia Medical Center.
Disclosures: The study was supported by the ziMS Foundation.
Citation: Engel CE et al. ACTRIMS Forum 2019, Poster 307.
Key clinical point: Patients with multiple sclerosis report a wide range of concerns about family planning and pregnancy.
Major finding: Of the 137 respondents who did not become pregnant following diagnosis, 22 (16%) indicated that their decision was driven by multiple sclerosis–related concerns, including MS worsening with pregnancy (64%).
Study details: A survey of 174 women with confirmed MS diagnosis who received care at the University of Virginia Medical Center.
Disclosures: The study was supported by the ziMS Foundation.
Citation: Engel CE et al. ACTRIMS Forum 2019, Poster 307.
High pCR rate in HPV+ HNSCC with nivolumab/SBRT
ATLANTA – For patients with locally advanced head and neck squamous cell carcinomas positive for human papillomavirus type 16, neoadjuvant therapy with the immune checkpoint inhibitor nivolumab combined with stereotactic body radiation therapy (SBRT) was associated with high response rates and a lower toxicity profile compared with the current standard of care, results of a phase 1/1b study suggest.
All of five patients treated with SBRT doses of 8 Gy per day for 5 days (40 Gy total) had pathologic complete responses (pCR), as did four of five patients treated at a deescalated SBRT dose of 8 Gy on alternating days for 3 days (24 Gy total), reported Rom S. Leidner, MD, of Providence Cancer Center in Portland, Ore.
“We’ve met the primary endpoint. This approach certainly was safe as far as not preventing definitive surgery. The potency was much greater than expected, with a pCR rate of 90% and a major response in 100% of patients,” he said at the annual meeting of the American Association for Cancer Research.
Dr. Leidner and colleagues are investigating therapies for locally advanced HPV-associated head and neck squamous cell carcinoma (HNSCC) that are as effective as but less toxic than the current standard of care: definitive chemoradiotherapy or surgery followed by risk-adapted adjuvant radiotherapy with or without chemotherapy.
They enrolled 10 patients, all men, with a mean age of 64.5 years. Seven patients had HPV16-positive oropharyngeal HNSCC, and three had unknown primary HNSCC (HPV-positive lymph nodes in the neck without an identifiable mucosal primary site). All patients had clinical indications for adjuvant radiotherapy or upfront transoral robotic surgery (TORS) but were ineligible because of tumor size.
The patients were assigned to one of two dose-finding cohorts in groups of five each to receive nivolumab (Opdivo) 240 mg intravenously every other week for three cycles prior to surgery, with SBRT to gross tumor volume plus 3 mm delivered between the first and second doses of nivolumab.
One cohort of patients received SBRT 8 Gy daily for 5 consecutive days (Monday-Friday), and the other received deescalated SBRT 8 Gy delivered on alternating days (Monday, Wednesday, Friday).
Patients underwent surgery 5 weeks after SBRT, and 4 weeks after surgery were started on adjuvant nivolumab 480 mg IV every 4 weeks for three cycles.
The trial met its primary endpoint of fewer than one-third of patients having an unplanned surgical delay. None of the 10 patients required a surgical delay, in fact.
Although all patients had radiologic evidence of tumor shrinkage prior to surgery, there were no complete responses according to Response Criteria in Solid Tumors (RECIST, version 1.1). Seven patients had a partial response (PR), and three had stable disease.
Dr. Leidner noted that when a patient with stable disease according to RECIST went to surgery “we found a [pCR] in the primary site, and residual cancer in the neck nodes with less than 10% viable tumor cells and evidence of immune eradication.”
As noted, all five patients in the 40-Gy dose group had complete pathologic responses, as did four of the five patients in the deescalated dose group. The remaining patient in this group had a major pathologic response, with less than 10% residual tumor.
“The secondary tissue endpoint far exceeded our expectations on this trial,” Dr. Leidner said.
There were no reports of acute toxicity in the neoadjuvant phase, but delayed mucositis (grade 1 or 2) and immune-related grade 1 dermatologic and rhinitis events were seen. Mucositis resolved by week 4 in all patients, at least 2 weeks before surgery.
Postoperative delayed toxicities up to grade 3 were seen, with delays in mucosal healing in patients who underwent mucosal resections; there were no cases of delayed healing among patients who underwent neck dissection only.
Grade 3 oropharyngeal pain requiring opiates for more than 4 weeks after surgery was seen in both cohorts, but lasted longer among patients in the 8-Gy-times-5 cohort.
Half of all patients were found to have adrenal insufficiency, a rate higher than that previously reported with the use of anti-PD-1 immune checkpoint inhibitors in HNSCC, Dr. Leidner said.
“Clinically we’re seeing, as one might expect, substantially reduced xerostomia and ageusia, but that was not formally measured,” he said.
Based on the study findings, investigations are proceeding at the deescalated dose.
Invited discussant Christine H. Chung, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, did not appear to share Dr. Leidner’s enthusiasm for the approach, saying that “overall, path CR in already resectable patients with an extremely high cure rate may not be clinically meaningful.”
She said that the role of adjuvant nivolumab following neoadjuvant nivolumab, radiotherapy, and surgery in HPV-positive patients is unclear, and that “the approach may be more suitable for HPV-negative patients with poor prognosis and in need of treatment intensification.”
Providence Cancer Center sponsored the study. Dr. Leidner reported having no relevant disclosures. Dr. Chung reported research funding from Lilly Oncology, and advisory board honoraria from BMS, CUE, and Ignyta.
SOURCE: Leidner RS et al. AACR 2019, Abstract CT182.
ATLANTA – For patients with locally advanced head and neck squamous cell carcinomas positive for human papillomavirus type 16, neoadjuvant therapy with the immune checkpoint inhibitor nivolumab combined with stereotactic body radiation therapy (SBRT) was associated with high response rates and a lower toxicity profile compared with the current standard of care, results of a phase 1/1b study suggest.
All of five patients treated with SBRT doses of 8 Gy per day for 5 days (40 Gy total) had pathologic complete responses (pCR), as did four of five patients treated at a deescalated SBRT dose of 8 Gy on alternating days for 3 days (24 Gy total), reported Rom S. Leidner, MD, of Providence Cancer Center in Portland, Ore.
“We’ve met the primary endpoint. This approach certainly was safe as far as not preventing definitive surgery. The potency was much greater than expected, with a pCR rate of 90% and a major response in 100% of patients,” he said at the annual meeting of the American Association for Cancer Research.
Dr. Leidner and colleagues are investigating therapies for locally advanced HPV-associated head and neck squamous cell carcinoma (HNSCC) that are as effective as but less toxic than the current standard of care: definitive chemoradiotherapy or surgery followed by risk-adapted adjuvant radiotherapy with or without chemotherapy.
They enrolled 10 patients, all men, with a mean age of 64.5 years. Seven patients had HPV16-positive oropharyngeal HNSCC, and three had unknown primary HNSCC (HPV-positive lymph nodes in the neck without an identifiable mucosal primary site). All patients had clinical indications for adjuvant radiotherapy or upfront transoral robotic surgery (TORS) but were ineligible because of tumor size.
The patients were assigned to one of two dose-finding cohorts in groups of five each to receive nivolumab (Opdivo) 240 mg intravenously every other week for three cycles prior to surgery, with SBRT to gross tumor volume plus 3 mm delivered between the first and second doses of nivolumab.
One cohort of patients received SBRT 8 Gy daily for 5 consecutive days (Monday-Friday), and the other received deescalated SBRT 8 Gy delivered on alternating days (Monday, Wednesday, Friday).
Patients underwent surgery 5 weeks after SBRT, and 4 weeks after surgery were started on adjuvant nivolumab 480 mg IV every 4 weeks for three cycles.
The trial met its primary endpoint of fewer than one-third of patients having an unplanned surgical delay. None of the 10 patients required a surgical delay, in fact.
Although all patients had radiologic evidence of tumor shrinkage prior to surgery, there were no complete responses according to Response Criteria in Solid Tumors (RECIST, version 1.1). Seven patients had a partial response (PR), and three had stable disease.
Dr. Leidner noted that when a patient with stable disease according to RECIST went to surgery “we found a [pCR] in the primary site, and residual cancer in the neck nodes with less than 10% viable tumor cells and evidence of immune eradication.”
As noted, all five patients in the 40-Gy dose group had complete pathologic responses, as did four of the five patients in the deescalated dose group. The remaining patient in this group had a major pathologic response, with less than 10% residual tumor.
“The secondary tissue endpoint far exceeded our expectations on this trial,” Dr. Leidner said.
There were no reports of acute toxicity in the neoadjuvant phase, but delayed mucositis (grade 1 or 2) and immune-related grade 1 dermatologic and rhinitis events were seen. Mucositis resolved by week 4 in all patients, at least 2 weeks before surgery.
Postoperative delayed toxicities up to grade 3 were seen, with delays in mucosal healing in patients who underwent mucosal resections; there were no cases of delayed healing among patients who underwent neck dissection only.
Grade 3 oropharyngeal pain requiring opiates for more than 4 weeks after surgery was seen in both cohorts, but lasted longer among patients in the 8-Gy-times-5 cohort.
Half of all patients were found to have adrenal insufficiency, a rate higher than that previously reported with the use of anti-PD-1 immune checkpoint inhibitors in HNSCC, Dr. Leidner said.
“Clinically we’re seeing, as one might expect, substantially reduced xerostomia and ageusia, but that was not formally measured,” he said.
Based on the study findings, investigations are proceeding at the deescalated dose.
Invited discussant Christine H. Chung, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, did not appear to share Dr. Leidner’s enthusiasm for the approach, saying that “overall, path CR in already resectable patients with an extremely high cure rate may not be clinically meaningful.”
She said that the role of adjuvant nivolumab following neoadjuvant nivolumab, radiotherapy, and surgery in HPV-positive patients is unclear, and that “the approach may be more suitable for HPV-negative patients with poor prognosis and in need of treatment intensification.”
Providence Cancer Center sponsored the study. Dr. Leidner reported having no relevant disclosures. Dr. Chung reported research funding from Lilly Oncology, and advisory board honoraria from BMS, CUE, and Ignyta.
SOURCE: Leidner RS et al. AACR 2019, Abstract CT182.
ATLANTA – For patients with locally advanced head and neck squamous cell carcinomas positive for human papillomavirus type 16, neoadjuvant therapy with the immune checkpoint inhibitor nivolumab combined with stereotactic body radiation therapy (SBRT) was associated with high response rates and a lower toxicity profile compared with the current standard of care, results of a phase 1/1b study suggest.
All of five patients treated with SBRT doses of 8 Gy per day for 5 days (40 Gy total) had pathologic complete responses (pCR), as did four of five patients treated at a deescalated SBRT dose of 8 Gy on alternating days for 3 days (24 Gy total), reported Rom S. Leidner, MD, of Providence Cancer Center in Portland, Ore.
“We’ve met the primary endpoint. This approach certainly was safe as far as not preventing definitive surgery. The potency was much greater than expected, with a pCR rate of 90% and a major response in 100% of patients,” he said at the annual meeting of the American Association for Cancer Research.
Dr. Leidner and colleagues are investigating therapies for locally advanced HPV-associated head and neck squamous cell carcinoma (HNSCC) that are as effective as but less toxic than the current standard of care: definitive chemoradiotherapy or surgery followed by risk-adapted adjuvant radiotherapy with or without chemotherapy.
They enrolled 10 patients, all men, with a mean age of 64.5 years. Seven patients had HPV16-positive oropharyngeal HNSCC, and three had unknown primary HNSCC (HPV-positive lymph nodes in the neck without an identifiable mucosal primary site). All patients had clinical indications for adjuvant radiotherapy or upfront transoral robotic surgery (TORS) but were ineligible because of tumor size.
The patients were assigned to one of two dose-finding cohorts in groups of five each to receive nivolumab (Opdivo) 240 mg intravenously every other week for three cycles prior to surgery, with SBRT to gross tumor volume plus 3 mm delivered between the first and second doses of nivolumab.
One cohort of patients received SBRT 8 Gy daily for 5 consecutive days (Monday-Friday), and the other received deescalated SBRT 8 Gy delivered on alternating days (Monday, Wednesday, Friday).
Patients underwent surgery 5 weeks after SBRT, and 4 weeks after surgery were started on adjuvant nivolumab 480 mg IV every 4 weeks for three cycles.
The trial met its primary endpoint of fewer than one-third of patients having an unplanned surgical delay. None of the 10 patients required a surgical delay, in fact.
Although all patients had radiologic evidence of tumor shrinkage prior to surgery, there were no complete responses according to Response Criteria in Solid Tumors (RECIST, version 1.1). Seven patients had a partial response (PR), and three had stable disease.
Dr. Leidner noted that when a patient with stable disease according to RECIST went to surgery “we found a [pCR] in the primary site, and residual cancer in the neck nodes with less than 10% viable tumor cells and evidence of immune eradication.”
As noted, all five patients in the 40-Gy dose group had complete pathologic responses, as did four of the five patients in the deescalated dose group. The remaining patient in this group had a major pathologic response, with less than 10% residual tumor.
“The secondary tissue endpoint far exceeded our expectations on this trial,” Dr. Leidner said.
There were no reports of acute toxicity in the neoadjuvant phase, but delayed mucositis (grade 1 or 2) and immune-related grade 1 dermatologic and rhinitis events were seen. Mucositis resolved by week 4 in all patients, at least 2 weeks before surgery.
Postoperative delayed toxicities up to grade 3 were seen, with delays in mucosal healing in patients who underwent mucosal resections; there were no cases of delayed healing among patients who underwent neck dissection only.
Grade 3 oropharyngeal pain requiring opiates for more than 4 weeks after surgery was seen in both cohorts, but lasted longer among patients in the 8-Gy-times-5 cohort.
Half of all patients were found to have adrenal insufficiency, a rate higher than that previously reported with the use of anti-PD-1 immune checkpoint inhibitors in HNSCC, Dr. Leidner said.
“Clinically we’re seeing, as one might expect, substantially reduced xerostomia and ageusia, but that was not formally measured,” he said.
Based on the study findings, investigations are proceeding at the deescalated dose.
Invited discussant Christine H. Chung, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, did not appear to share Dr. Leidner’s enthusiasm for the approach, saying that “overall, path CR in already resectable patients with an extremely high cure rate may not be clinically meaningful.”
She said that the role of adjuvant nivolumab following neoadjuvant nivolumab, radiotherapy, and surgery in HPV-positive patients is unclear, and that “the approach may be more suitable for HPV-negative patients with poor prognosis and in need of treatment intensification.”
Providence Cancer Center sponsored the study. Dr. Leidner reported having no relevant disclosures. Dr. Chung reported research funding from Lilly Oncology, and advisory board honoraria from BMS, CUE, and Ignyta.
SOURCE: Leidner RS et al. AACR 2019, Abstract CT182.
REPORTING FROM AACR 2019
Report card may foretell achalasia surgery outcomes
BALTIMORE – The Eckardt score has been established as a tool to evaluate outcomes of surgery for achalasia, but researchers have developed a report card that uses multiple variables that may provide a more accurate picture of surgical outcomes, according to results of study reported at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons.
“The use of an accurate score to assess outcomes after achalasia surgery shows outstanding results,” said Ealaf Shemmeri, MD, of Swedish Medical Center in Seattle. “Using patient-reported symptoms, objective measures, and rates of reinterventions organized into a report card provides a more comprehensive and informative view.”
The Eckardt score evaluates four symptoms to evaluate outcomes of surgery to treat achalasia: weight loss, retrosternal pain, regurgitation, and dysphagia. “However, it does not address the other changes that can occur after myotomy, including the quality of swallowing and the onset of reflux disease,” she said. “Thus, there is a need for a more comprehensive assessment of quality after achalasia treatment.”
So the Swedish investigators set out to devise a report card that provides “a comprehensive and informative assessment” of surgical myotomy outcomes, she said. This involved a retrospective, single-center chart review of 185 patients who had surgical myotomy for primary achalasia from 2005 to 2017.
To determine patient-reported outcomes, the report card defines success as an Eckardt score below 3, Dakkak dysphagia score above 40, and GERD-HRQL (health-related quality of life) score below 10. The objective measures consisted of DeMeester (pH) score below 14.72, no column at 5 minutes on timed barium swallow, normalized integrated relaxation pressure less than 15 on manometry, and absence of esophagitis on endoscopy. For the third pillar of the report card, no reintervention was recorded as a success, Dr. Shemmeri said.
Regarding the etiology of achalasia in the study population, 42 had type 1, 109 had type 2, and 34 had type 3. A total of 71 patients had per oral endoscopic myotomy and 114 had Heller myotomy, 92 with Dor fundoplication and 20 with Toupet. Major perioperative complications included four per oral endoscopic myotomy patients who developed a leak requiring intervention. Six patients required return to the operating room for persistent dysphagia, Dr. Shemmeri said.
After the procedures, 93% of study patients reported an Eckardt score less than 3. However, only 45% have a Dakkak dysphagia score greater than 40 and 71% had a GERD-HRQL score less than 10, Dr. Shemmeri said. The objective measures told a similar story: Integrated relaxation pressure normalized in 80%, barium clearance was achieved in 61%, normal esophageal mucosa was recorded in 71%, “but pH testing was normal only 50% of the time,” Dr. Shemmeri said.
“The final success of not needing intervention is 79%,” she said. At this point in the study, 139 patients were available for follow-up. Among the 29 who needed reintervention, 19 had dilation below 20 mm Hg, 3 underwent pneumatic dilation, and 2 had botulinum toxin. Two patients required a redo myotomy, two had antireflux surgery, and one had an esophagectomy.
“When you only focus on a singular outcome, you can miss the whole story that occurs after myotomy,” Dr. Shemmeri said. “Providing a comprehensive tool gives you the ability to identify areas for improvement in your achalasia practice. Its simplicity allows it to be applied in various settings.” In the academic setting, it can be a tool for evaluating technologies and approaches for postmyotomy management. In hospitals and surgeons’ practices, it can aid in quality improvement, comparative outcomes research, and in evaluating operative approaches to myotomy.
The outcomes highlight the high prevalence of GERD, thus stressing the importance of pH testing after myotomy, Dr. Shemmeri said. Her study team recommends pH testing at 6-month follow-up because patients may not always self-report the extent of esophagitis present. Coauthor Brian Louie, MD, also of Swedish Medical Center, added during the discussion that ongoing follow-up of achalasia patients is necessary to address issues patients encounter with their swallowing over time.
Dr. Shemmeri had no relevant financial relationships to disclose. Dr. Louie reported relationships with Boston Scientific, ERBE, and Olympus.
SOURCE: Shemmeri E et al. SAGES 2019, Presentation S085.
BALTIMORE – The Eckardt score has been established as a tool to evaluate outcomes of surgery for achalasia, but researchers have developed a report card that uses multiple variables that may provide a more accurate picture of surgical outcomes, according to results of study reported at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons.
“The use of an accurate score to assess outcomes after achalasia surgery shows outstanding results,” said Ealaf Shemmeri, MD, of Swedish Medical Center in Seattle. “Using patient-reported symptoms, objective measures, and rates of reinterventions organized into a report card provides a more comprehensive and informative view.”
The Eckardt score evaluates four symptoms to evaluate outcomes of surgery to treat achalasia: weight loss, retrosternal pain, regurgitation, and dysphagia. “However, it does not address the other changes that can occur after myotomy, including the quality of swallowing and the onset of reflux disease,” she said. “Thus, there is a need for a more comprehensive assessment of quality after achalasia treatment.”
So the Swedish investigators set out to devise a report card that provides “a comprehensive and informative assessment” of surgical myotomy outcomes, she said. This involved a retrospective, single-center chart review of 185 patients who had surgical myotomy for primary achalasia from 2005 to 2017.
To determine patient-reported outcomes, the report card defines success as an Eckardt score below 3, Dakkak dysphagia score above 40, and GERD-HRQL (health-related quality of life) score below 10. The objective measures consisted of DeMeester (pH) score below 14.72, no column at 5 minutes on timed barium swallow, normalized integrated relaxation pressure less than 15 on manometry, and absence of esophagitis on endoscopy. For the third pillar of the report card, no reintervention was recorded as a success, Dr. Shemmeri said.
Regarding the etiology of achalasia in the study population, 42 had type 1, 109 had type 2, and 34 had type 3. A total of 71 patients had per oral endoscopic myotomy and 114 had Heller myotomy, 92 with Dor fundoplication and 20 with Toupet. Major perioperative complications included four per oral endoscopic myotomy patients who developed a leak requiring intervention. Six patients required return to the operating room for persistent dysphagia, Dr. Shemmeri said.
After the procedures, 93% of study patients reported an Eckardt score less than 3. However, only 45% have a Dakkak dysphagia score greater than 40 and 71% had a GERD-HRQL score less than 10, Dr. Shemmeri said. The objective measures told a similar story: Integrated relaxation pressure normalized in 80%, barium clearance was achieved in 61%, normal esophageal mucosa was recorded in 71%, “but pH testing was normal only 50% of the time,” Dr. Shemmeri said.
“The final success of not needing intervention is 79%,” she said. At this point in the study, 139 patients were available for follow-up. Among the 29 who needed reintervention, 19 had dilation below 20 mm Hg, 3 underwent pneumatic dilation, and 2 had botulinum toxin. Two patients required a redo myotomy, two had antireflux surgery, and one had an esophagectomy.
“When you only focus on a singular outcome, you can miss the whole story that occurs after myotomy,” Dr. Shemmeri said. “Providing a comprehensive tool gives you the ability to identify areas for improvement in your achalasia practice. Its simplicity allows it to be applied in various settings.” In the academic setting, it can be a tool for evaluating technologies and approaches for postmyotomy management. In hospitals and surgeons’ practices, it can aid in quality improvement, comparative outcomes research, and in evaluating operative approaches to myotomy.
The outcomes highlight the high prevalence of GERD, thus stressing the importance of pH testing after myotomy, Dr. Shemmeri said. Her study team recommends pH testing at 6-month follow-up because patients may not always self-report the extent of esophagitis present. Coauthor Brian Louie, MD, also of Swedish Medical Center, added during the discussion that ongoing follow-up of achalasia patients is necessary to address issues patients encounter with their swallowing over time.
Dr. Shemmeri had no relevant financial relationships to disclose. Dr. Louie reported relationships with Boston Scientific, ERBE, and Olympus.
SOURCE: Shemmeri E et al. SAGES 2019, Presentation S085.
BALTIMORE – The Eckardt score has been established as a tool to evaluate outcomes of surgery for achalasia, but researchers have developed a report card that uses multiple variables that may provide a more accurate picture of surgical outcomes, according to results of study reported at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons.
“The use of an accurate score to assess outcomes after achalasia surgery shows outstanding results,” said Ealaf Shemmeri, MD, of Swedish Medical Center in Seattle. “Using patient-reported symptoms, objective measures, and rates of reinterventions organized into a report card provides a more comprehensive and informative view.”
The Eckardt score evaluates four symptoms to evaluate outcomes of surgery to treat achalasia: weight loss, retrosternal pain, regurgitation, and dysphagia. “However, it does not address the other changes that can occur after myotomy, including the quality of swallowing and the onset of reflux disease,” she said. “Thus, there is a need for a more comprehensive assessment of quality after achalasia treatment.”
So the Swedish investigators set out to devise a report card that provides “a comprehensive and informative assessment” of surgical myotomy outcomes, she said. This involved a retrospective, single-center chart review of 185 patients who had surgical myotomy for primary achalasia from 2005 to 2017.
To determine patient-reported outcomes, the report card defines success as an Eckardt score below 3, Dakkak dysphagia score above 40, and GERD-HRQL (health-related quality of life) score below 10. The objective measures consisted of DeMeester (pH) score below 14.72, no column at 5 minutes on timed barium swallow, normalized integrated relaxation pressure less than 15 on manometry, and absence of esophagitis on endoscopy. For the third pillar of the report card, no reintervention was recorded as a success, Dr. Shemmeri said.
Regarding the etiology of achalasia in the study population, 42 had type 1, 109 had type 2, and 34 had type 3. A total of 71 patients had per oral endoscopic myotomy and 114 had Heller myotomy, 92 with Dor fundoplication and 20 with Toupet. Major perioperative complications included four per oral endoscopic myotomy patients who developed a leak requiring intervention. Six patients required return to the operating room for persistent dysphagia, Dr. Shemmeri said.
After the procedures, 93% of study patients reported an Eckardt score less than 3. However, only 45% have a Dakkak dysphagia score greater than 40 and 71% had a GERD-HRQL score less than 10, Dr. Shemmeri said. The objective measures told a similar story: Integrated relaxation pressure normalized in 80%, barium clearance was achieved in 61%, normal esophageal mucosa was recorded in 71%, “but pH testing was normal only 50% of the time,” Dr. Shemmeri said.
“The final success of not needing intervention is 79%,” she said. At this point in the study, 139 patients were available for follow-up. Among the 29 who needed reintervention, 19 had dilation below 20 mm Hg, 3 underwent pneumatic dilation, and 2 had botulinum toxin. Two patients required a redo myotomy, two had antireflux surgery, and one had an esophagectomy.
“When you only focus on a singular outcome, you can miss the whole story that occurs after myotomy,” Dr. Shemmeri said. “Providing a comprehensive tool gives you the ability to identify areas for improvement in your achalasia practice. Its simplicity allows it to be applied in various settings.” In the academic setting, it can be a tool for evaluating technologies and approaches for postmyotomy management. In hospitals and surgeons’ practices, it can aid in quality improvement, comparative outcomes research, and in evaluating operative approaches to myotomy.
The outcomes highlight the high prevalence of GERD, thus stressing the importance of pH testing after myotomy, Dr. Shemmeri said. Her study team recommends pH testing at 6-month follow-up because patients may not always self-report the extent of esophagitis present. Coauthor Brian Louie, MD, also of Swedish Medical Center, added during the discussion that ongoing follow-up of achalasia patients is necessary to address issues patients encounter with their swallowing over time.
Dr. Shemmeri had no relevant financial relationships to disclose. Dr. Louie reported relationships with Boston Scientific, ERBE, and Olympus.
SOURCE: Shemmeri E et al. SAGES 2019, Presentation S085.
REPORTING FROM SAGES 2019
Reducing sepsis mortality
The CDC estimates that 1.7 million people in the United States acquire sepsis annually; sepsis accounts for nearly 270,000 patient deaths per year.
Decreasing mortality and improving patient outcomes requires early detection and appropriate timely treatment. The Joint Commission Center for Transforming Healthcare’s recent sepsis project demonstrated this by analyzing root causes and reducing sepsis mortality with five leading hospitals by an aggregate of nearly 25%.
“Most organizations can tell you how they are doing with regard to whether or not they are ordering lactates or fluids, but many can’t tell you where in the process these elements are failing,” said Kelly Barnes, Black Belt III, Joint Commission Center for Transforming Healthcare. “For instance, is the issue in ordering lactates, drawing lactates, or getting the results of lactates in a timely manner? The key is to understand where in the process things are breaking down to identify what solutions an organization needs to put in place.”
During the Joint Commission project, one organization found that patients had inadequate fluid resuscitation due to staff fear of fluid overload, while another organization found they had issues with fluids being disconnected when patients were taken for tests and then not reconnected – different problems that needed different solutions.
The Joint Commission Center for Transforming Healthcare is currently developing a Targeted Solutions Tool® (TST®), scheduled for release in 2019, to help organizations determine their issues with sepsis recognition and barriers to meeting sepsis bundle element requirements and implement targeted solutions to address their specific issues. The tool will be available free of charge to all Joint Commission-accredited customers.
Reference
1. “Hospital-Wide Sepsis Project Reduces Mortality by Nearly 25 Percent,” Kelly Barnes, The Joint Commission Center for Transforming Healthcare. 2018, Sep 25.
The CDC estimates that 1.7 million people in the United States acquire sepsis annually; sepsis accounts for nearly 270,000 patient deaths per year.
Decreasing mortality and improving patient outcomes requires early detection and appropriate timely treatment. The Joint Commission Center for Transforming Healthcare’s recent sepsis project demonstrated this by analyzing root causes and reducing sepsis mortality with five leading hospitals by an aggregate of nearly 25%.
“Most organizations can tell you how they are doing with regard to whether or not they are ordering lactates or fluids, but many can’t tell you where in the process these elements are failing,” said Kelly Barnes, Black Belt III, Joint Commission Center for Transforming Healthcare. “For instance, is the issue in ordering lactates, drawing lactates, or getting the results of lactates in a timely manner? The key is to understand where in the process things are breaking down to identify what solutions an organization needs to put in place.”
During the Joint Commission project, one organization found that patients had inadequate fluid resuscitation due to staff fear of fluid overload, while another organization found they had issues with fluids being disconnected when patients were taken for tests and then not reconnected – different problems that needed different solutions.
The Joint Commission Center for Transforming Healthcare is currently developing a Targeted Solutions Tool® (TST®), scheduled for release in 2019, to help organizations determine their issues with sepsis recognition and barriers to meeting sepsis bundle element requirements and implement targeted solutions to address their specific issues. The tool will be available free of charge to all Joint Commission-accredited customers.
Reference
1. “Hospital-Wide Sepsis Project Reduces Mortality by Nearly 25 Percent,” Kelly Barnes, The Joint Commission Center for Transforming Healthcare. 2018, Sep 25.
The CDC estimates that 1.7 million people in the United States acquire sepsis annually; sepsis accounts for nearly 270,000 patient deaths per year.
Decreasing mortality and improving patient outcomes requires early detection and appropriate timely treatment. The Joint Commission Center for Transforming Healthcare’s recent sepsis project demonstrated this by analyzing root causes and reducing sepsis mortality with five leading hospitals by an aggregate of nearly 25%.
“Most organizations can tell you how they are doing with regard to whether or not they are ordering lactates or fluids, but many can’t tell you where in the process these elements are failing,” said Kelly Barnes, Black Belt III, Joint Commission Center for Transforming Healthcare. “For instance, is the issue in ordering lactates, drawing lactates, or getting the results of lactates in a timely manner? The key is to understand where in the process things are breaking down to identify what solutions an organization needs to put in place.”
During the Joint Commission project, one organization found that patients had inadequate fluid resuscitation due to staff fear of fluid overload, while another organization found they had issues with fluids being disconnected when patients were taken for tests and then not reconnected – different problems that needed different solutions.
The Joint Commission Center for Transforming Healthcare is currently developing a Targeted Solutions Tool® (TST®), scheduled for release in 2019, to help organizations determine their issues with sepsis recognition and barriers to meeting sepsis bundle element requirements and implement targeted solutions to address their specific issues. The tool will be available free of charge to all Joint Commission-accredited customers.
Reference
1. “Hospital-Wide Sepsis Project Reduces Mortality by Nearly 25 Percent,” Kelly Barnes, The Joint Commission Center for Transforming Healthcare. 2018, Sep 25.
Plasma Metabolome Analysis in Migraine
In a large-scale plasma metabolome analysis, metabolic profiling of plasma yielded alterations in high-density lipoprotein (HDL) metabolism in patients with migraine and decreased omega-3 fatty acids only in male migraineurs, a new study found. Researchers sought to identify a plasma metabolomic biomarker signature for migraine. Plasma samples from 8 Dutch cohorts (n=10,153: 2800 migraine patients and 7353 controls) were profiled on a H-NMR-based metabolomics platform to quantify 146 individual metabolites and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Among the findings:
- Decreases in the level of apolipoprotein A1 and free cholesterol total lipid ratio present in small HDL subspecies were associated with migraine status.
- A decreased level of omega-3 fatty acids was associated with migraine in male participants only.
- Global test analysis supported that HDL traits were associated with migraine status.
Onderwater GLJ, Ligthart L, Bot M, et al. Large-scale metabolome analysis reveals alterations in HDL metabolism in migraine. [Published online ahead of print April 3, 2019]. Neurology. doi:10.1212/WNL.0000000000007313.
In a large-scale plasma metabolome analysis, metabolic profiling of plasma yielded alterations in high-density lipoprotein (HDL) metabolism in patients with migraine and decreased omega-3 fatty acids only in male migraineurs, a new study found. Researchers sought to identify a plasma metabolomic biomarker signature for migraine. Plasma samples from 8 Dutch cohorts (n=10,153: 2800 migraine patients and 7353 controls) were profiled on a H-NMR-based metabolomics platform to quantify 146 individual metabolites and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Among the findings:
- Decreases in the level of apolipoprotein A1 and free cholesterol total lipid ratio present in small HDL subspecies were associated with migraine status.
- A decreased level of omega-3 fatty acids was associated with migraine in male participants only.
- Global test analysis supported that HDL traits were associated with migraine status.
Onderwater GLJ, Ligthart L, Bot M, et al. Large-scale metabolome analysis reveals alterations in HDL metabolism in migraine. [Published online ahead of print April 3, 2019]. Neurology. doi:10.1212/WNL.0000000000007313.
In a large-scale plasma metabolome analysis, metabolic profiling of plasma yielded alterations in high-density lipoprotein (HDL) metabolism in patients with migraine and decreased omega-3 fatty acids only in male migraineurs, a new study found. Researchers sought to identify a plasma metabolomic biomarker signature for migraine. Plasma samples from 8 Dutch cohorts (n=10,153: 2800 migraine patients and 7353 controls) were profiled on a H-NMR-based metabolomics platform to quantify 146 individual metabolites and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Among the findings:
- Decreases in the level of apolipoprotein A1 and free cholesterol total lipid ratio present in small HDL subspecies were associated with migraine status.
- A decreased level of omega-3 fatty acids was associated with migraine in male participants only.
- Global test analysis supported that HDL traits were associated with migraine status.
Onderwater GLJ, Ligthart L, Bot M, et al. Large-scale metabolome analysis reveals alterations in HDL metabolism in migraine. [Published online ahead of print April 3, 2019]. Neurology. doi:10.1212/WNL.0000000000007313.
Hyperhidrosis: Survey of the Cutis Editorial Board
To improve patient care and outcomes, leading dermatologists from the Cutis Editorial Board answered 5 questions on hyperhidrosis. Here’s what we found.
In which areas do patients report hyperhidrosis most frequently?
Nearly 70% of dermatologists see patients with hyperhidrosis of the axillae, followed by the palms and soles (27%). Only 4% of dermatologists indicated that they see hyperhidrosis all over the body.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Hyperhidrosis affects up to 5% of the US population and may remarkably affect quality of life. Primary hyperhidrosis accounts for 93% of cases. Before puberty, hyperhidrosis affects the palms and soles in up to 90% of patients. In adults, the axillae are most commonly affected (51%), followed by plantar (30%), palmar (24%), and facial (10%) areas (Strutton et al).
Next page: Topical treatment
Approximately what percentage of patients are satisfied with topical treatments for hyperhidrosis?
The majority of dermatologists (88%) reported that less than half of their patients are satisfied with topical treatments for hyperhidrosis. Only 12% indicated that 51% to 70% of their patients were satisfied, and none of the respondents indicated that >70% were satisfied.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
There is clearly a need for safe and effective treatments for hyperhidrosis. Treatment of hyperhidrosis should include lifestyle and behavioral modifications. It is helpful to try to avoid hot crowded rooms when feasible, as well as stress, tight clothing, occlusive shoes, alcohol, and spicy foods. Patients should be instructed on proper use of medications, as well as the need to continue therapy for maintenance. Patients should be encouraged to follow up for alternative treatment options in cases of therapy failure.
Next page: Botulinum toxin
On average, how long do the effects of botulinum toxin last in your axillary hyperhidrosis patients?
The effects of botulinum toxin last at least 4 months and up to 6 months in most patients, according to 58% of dermatologists surveyed. Thirty percent reported 2 to 4 months, and 13% reported more than 6 months.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
OnabotulinumtoxinA is approved by the US Food and Drug Administration for severe primary axillary hyperhidrosis. Injections are ideally placed at the dermal-subcutaneous junction, with 1 unit placed every 1 to 2 cm. Dosing is 50 to 100 U per axilla with higher dosing required for the palms and soles (off label). Reported efficacy for axillary hyperhidrosis is 82% to 87%; however, 50% of patients with plantar hyperhidrosis are dissatisfied with the treatment. Sweat reduction is most apparent after 2 weeks and typically persists 6 to 8 months in clinical trials (Botox package insert).
Next page: Systemic anticholinergics
When prescribing systemic anticholinergics for hyperhidrosis, what side effect is most common among your patients?
More than three-quarters of dermatologists (81%) reported that dry mouth is the most common side effect of systemic anticholinergics. Dry eyes is the second most common side effect (15%).
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Systemic anticholinergics are commonly used off label for the treatment of hyperhidrosis. Adverse effects include dry mouth, blurred vision, dry eyes, orthostatic hypotension, gastrointestinal, urinary retention, tachycardia, and drowsiness. Unfortunately, these side effects cause one-third of patients to discontinue treatment (Bajaj and Langtry). A slow escalation of the dose may increase tolerability and reduce these side effects. These anticholinergics should not be taken with other medications with anticholinergic activity to avoid exacerbating these side effects.
Next page: Surgical treatment
What percentage of patients require surgery for treatment of hyperhidrosis after topical, injectable, systemic options and devices have failed?
According to 62% of dermatologists, 10% or less of patients require surgery for treatment of hyperhidrosis after other therapies have failed. Almost one-third indicated that none of their patients require surgical treatment. None of the dermatologists surveyed reported that more than 60% of patients need surgery.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Surgery is an option to treat hyperhidrosis when conservative methods have failed. Surgical therapies include curettage, liposuction, and excision. A last resort is considered sympathectomy. Endoscopic thoracic sympathectomy is employed for palmar, facial, and axillary hyperhidrosis, while endoscopic lumbar sympathectomy is indicated for plantar hyperhidrosis.
Next page: More tips from derms
More Tips From Dermatologists
The dermatologists we polled had the following advice for their peers:
Patients with focal idiopathic hyperhidrosis of the axillae as well as palms/soles report that this condition interferes with the quality of life in major ways, from social interactions to professional interactions. They often don't even know they have a problem and internalize that they must be overly anxious about things. I have patients that buy 3 of the same shirts and change a few times a day, costing a great deal of money (plus cleaning bills for 3 shirts as well) and costing a great deal of wasted time when they could be doing something more productive. It's great that not only botulinum toxins can be helpful for the underarms but also even less-invasive topical anticholinergics (easy to use, no discomfort, predictable, and helping make treatment for axillary hyperhidrosis much more on the radar).—Joel L. Cohen, MD (Denver, Colorado)
More and more patients are presenting to request relief from hyperhidrosis, and increasingly in nontraditional areas (ie, areas other than the axilla and forehead). These include the palms and scalp most commonly, and then the breast, chest, and back. Patients with hyperhidrosis of the feet often present requesting help for their malodorous or smelly feet and shoes.—Fran E. Cook-Bolden, MD (New York, New York)
I have found that systemic hyperhidrosis has usually been responsive to oral glycopyrrolate. But localized hyperhidrosis is more difficult to treat. Glycopyrronium has made life so much easier for my axillary hyperhidrosis patients. Now I am waiting for some game changer for palms and soles.—Lawrence J. Green, MD (Washington, DC)
About This Survey
The survey was fielded electronically to Cutis Editorial Board Members within the United States from March 11, 2019, to April 8, 2019. A total of 26 usable responses were received.
Bajaj V, Langtry JA. Use of oral glycopyrronium bromide in hyperhidrosis. Br J Dermatol. 2007;157:118-121.
Botox [package insert]. Madison, NJ: Allergan, Inc; 2018.
Strutton DR, Kowalski JW, Glaser DA, et al. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: Results from a national survey. J Am Acad Dermatol. 2004;51:241-248.
To improve patient care and outcomes, leading dermatologists from the Cutis Editorial Board answered 5 questions on hyperhidrosis. Here’s what we found.
In which areas do patients report hyperhidrosis most frequently?
Nearly 70% of dermatologists see patients with hyperhidrosis of the axillae, followed by the palms and soles (27%). Only 4% of dermatologists indicated that they see hyperhidrosis all over the body.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Hyperhidrosis affects up to 5% of the US population and may remarkably affect quality of life. Primary hyperhidrosis accounts for 93% of cases. Before puberty, hyperhidrosis affects the palms and soles in up to 90% of patients. In adults, the axillae are most commonly affected (51%), followed by plantar (30%), palmar (24%), and facial (10%) areas (Strutton et al).
Next page: Topical treatment
Approximately what percentage of patients are satisfied with topical treatments for hyperhidrosis?
The majority of dermatologists (88%) reported that less than half of their patients are satisfied with topical treatments for hyperhidrosis. Only 12% indicated that 51% to 70% of their patients were satisfied, and none of the respondents indicated that >70% were satisfied.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
There is clearly a need for safe and effective treatments for hyperhidrosis. Treatment of hyperhidrosis should include lifestyle and behavioral modifications. It is helpful to try to avoid hot crowded rooms when feasible, as well as stress, tight clothing, occlusive shoes, alcohol, and spicy foods. Patients should be instructed on proper use of medications, as well as the need to continue therapy for maintenance. Patients should be encouraged to follow up for alternative treatment options in cases of therapy failure.
Next page: Botulinum toxin
On average, how long do the effects of botulinum toxin last in your axillary hyperhidrosis patients?
The effects of botulinum toxin last at least 4 months and up to 6 months in most patients, according to 58% of dermatologists surveyed. Thirty percent reported 2 to 4 months, and 13% reported more than 6 months.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
OnabotulinumtoxinA is approved by the US Food and Drug Administration for severe primary axillary hyperhidrosis. Injections are ideally placed at the dermal-subcutaneous junction, with 1 unit placed every 1 to 2 cm. Dosing is 50 to 100 U per axilla with higher dosing required for the palms and soles (off label). Reported efficacy for axillary hyperhidrosis is 82% to 87%; however, 50% of patients with plantar hyperhidrosis are dissatisfied with the treatment. Sweat reduction is most apparent after 2 weeks and typically persists 6 to 8 months in clinical trials (Botox package insert).
Next page: Systemic anticholinergics
When prescribing systemic anticholinergics for hyperhidrosis, what side effect is most common among your patients?
More than three-quarters of dermatologists (81%) reported that dry mouth is the most common side effect of systemic anticholinergics. Dry eyes is the second most common side effect (15%).
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Systemic anticholinergics are commonly used off label for the treatment of hyperhidrosis. Adverse effects include dry mouth, blurred vision, dry eyes, orthostatic hypotension, gastrointestinal, urinary retention, tachycardia, and drowsiness. Unfortunately, these side effects cause one-third of patients to discontinue treatment (Bajaj and Langtry). A slow escalation of the dose may increase tolerability and reduce these side effects. These anticholinergics should not be taken with other medications with anticholinergic activity to avoid exacerbating these side effects.
Next page: Surgical treatment
What percentage of patients require surgery for treatment of hyperhidrosis after topical, injectable, systemic options and devices have failed?
According to 62% of dermatologists, 10% or less of patients require surgery for treatment of hyperhidrosis after other therapies have failed. Almost one-third indicated that none of their patients require surgical treatment. None of the dermatologists surveyed reported that more than 60% of patients need surgery.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Surgery is an option to treat hyperhidrosis when conservative methods have failed. Surgical therapies include curettage, liposuction, and excision. A last resort is considered sympathectomy. Endoscopic thoracic sympathectomy is employed for palmar, facial, and axillary hyperhidrosis, while endoscopic lumbar sympathectomy is indicated for plantar hyperhidrosis.
Next page: More tips from derms
More Tips From Dermatologists
The dermatologists we polled had the following advice for their peers:
Patients with focal idiopathic hyperhidrosis of the axillae as well as palms/soles report that this condition interferes with the quality of life in major ways, from social interactions to professional interactions. They often don't even know they have a problem and internalize that they must be overly anxious about things. I have patients that buy 3 of the same shirts and change a few times a day, costing a great deal of money (plus cleaning bills for 3 shirts as well) and costing a great deal of wasted time when they could be doing something more productive. It's great that not only botulinum toxins can be helpful for the underarms but also even less-invasive topical anticholinergics (easy to use, no discomfort, predictable, and helping make treatment for axillary hyperhidrosis much more on the radar).—Joel L. Cohen, MD (Denver, Colorado)
More and more patients are presenting to request relief from hyperhidrosis, and increasingly in nontraditional areas (ie, areas other than the axilla and forehead). These include the palms and scalp most commonly, and then the breast, chest, and back. Patients with hyperhidrosis of the feet often present requesting help for their malodorous or smelly feet and shoes.—Fran E. Cook-Bolden, MD (New York, New York)
I have found that systemic hyperhidrosis has usually been responsive to oral glycopyrrolate. But localized hyperhidrosis is more difficult to treat. Glycopyrronium has made life so much easier for my axillary hyperhidrosis patients. Now I am waiting for some game changer for palms and soles.—Lawrence J. Green, MD (Washington, DC)
About This Survey
The survey was fielded electronically to Cutis Editorial Board Members within the United States from March 11, 2019, to April 8, 2019. A total of 26 usable responses were received.
To improve patient care and outcomes, leading dermatologists from the Cutis Editorial Board answered 5 questions on hyperhidrosis. Here’s what we found.
In which areas do patients report hyperhidrosis most frequently?
Nearly 70% of dermatologists see patients with hyperhidrosis of the axillae, followed by the palms and soles (27%). Only 4% of dermatologists indicated that they see hyperhidrosis all over the body.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Hyperhidrosis affects up to 5% of the US population and may remarkably affect quality of life. Primary hyperhidrosis accounts for 93% of cases. Before puberty, hyperhidrosis affects the palms and soles in up to 90% of patients. In adults, the axillae are most commonly affected (51%), followed by plantar (30%), palmar (24%), and facial (10%) areas (Strutton et al).
Next page: Topical treatment
Approximately what percentage of patients are satisfied with topical treatments for hyperhidrosis?
The majority of dermatologists (88%) reported that less than half of their patients are satisfied with topical treatments for hyperhidrosis. Only 12% indicated that 51% to 70% of their patients were satisfied, and none of the respondents indicated that >70% were satisfied.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
There is clearly a need for safe and effective treatments for hyperhidrosis. Treatment of hyperhidrosis should include lifestyle and behavioral modifications. It is helpful to try to avoid hot crowded rooms when feasible, as well as stress, tight clothing, occlusive shoes, alcohol, and spicy foods. Patients should be instructed on proper use of medications, as well as the need to continue therapy for maintenance. Patients should be encouraged to follow up for alternative treatment options in cases of therapy failure.
Next page: Botulinum toxin
On average, how long do the effects of botulinum toxin last in your axillary hyperhidrosis patients?
The effects of botulinum toxin last at least 4 months and up to 6 months in most patients, according to 58% of dermatologists surveyed. Thirty percent reported 2 to 4 months, and 13% reported more than 6 months.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
OnabotulinumtoxinA is approved by the US Food and Drug Administration for severe primary axillary hyperhidrosis. Injections are ideally placed at the dermal-subcutaneous junction, with 1 unit placed every 1 to 2 cm. Dosing is 50 to 100 U per axilla with higher dosing required for the palms and soles (off label). Reported efficacy for axillary hyperhidrosis is 82% to 87%; however, 50% of patients with plantar hyperhidrosis are dissatisfied with the treatment. Sweat reduction is most apparent after 2 weeks and typically persists 6 to 8 months in clinical trials (Botox package insert).
Next page: Systemic anticholinergics
When prescribing systemic anticholinergics for hyperhidrosis, what side effect is most common among your patients?
More than three-quarters of dermatologists (81%) reported that dry mouth is the most common side effect of systemic anticholinergics. Dry eyes is the second most common side effect (15%).
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Systemic anticholinergics are commonly used off label for the treatment of hyperhidrosis. Adverse effects include dry mouth, blurred vision, dry eyes, orthostatic hypotension, gastrointestinal, urinary retention, tachycardia, and drowsiness. Unfortunately, these side effects cause one-third of patients to discontinue treatment (Bajaj and Langtry). A slow escalation of the dose may increase tolerability and reduce these side effects. These anticholinergics should not be taken with other medications with anticholinergic activity to avoid exacerbating these side effects.
Next page: Surgical treatment
What percentage of patients require surgery for treatment of hyperhidrosis after topical, injectable, systemic options and devices have failed?
According to 62% of dermatologists, 10% or less of patients require surgery for treatment of hyperhidrosis after other therapies have failed. Almost one-third indicated that none of their patients require surgical treatment. None of the dermatologists surveyed reported that more than 60% of patients need surgery.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Surgery is an option to treat hyperhidrosis when conservative methods have failed. Surgical therapies include curettage, liposuction, and excision. A last resort is considered sympathectomy. Endoscopic thoracic sympathectomy is employed for palmar, facial, and axillary hyperhidrosis, while endoscopic lumbar sympathectomy is indicated for plantar hyperhidrosis.
Next page: More tips from derms
More Tips From Dermatologists
The dermatologists we polled had the following advice for their peers:
Patients with focal idiopathic hyperhidrosis of the axillae as well as palms/soles report that this condition interferes with the quality of life in major ways, from social interactions to professional interactions. They often don't even know they have a problem and internalize that they must be overly anxious about things. I have patients that buy 3 of the same shirts and change a few times a day, costing a great deal of money (plus cleaning bills for 3 shirts as well) and costing a great deal of wasted time when they could be doing something more productive. It's great that not only botulinum toxins can be helpful for the underarms but also even less-invasive topical anticholinergics (easy to use, no discomfort, predictable, and helping make treatment for axillary hyperhidrosis much more on the radar).—Joel L. Cohen, MD (Denver, Colorado)
More and more patients are presenting to request relief from hyperhidrosis, and increasingly in nontraditional areas (ie, areas other than the axilla and forehead). These include the palms and scalp most commonly, and then the breast, chest, and back. Patients with hyperhidrosis of the feet often present requesting help for their malodorous or smelly feet and shoes.—Fran E. Cook-Bolden, MD (New York, New York)
I have found that systemic hyperhidrosis has usually been responsive to oral glycopyrrolate. But localized hyperhidrosis is more difficult to treat. Glycopyrronium has made life so much easier for my axillary hyperhidrosis patients. Now I am waiting for some game changer for palms and soles.—Lawrence J. Green, MD (Washington, DC)
About This Survey
The survey was fielded electronically to Cutis Editorial Board Members within the United States from March 11, 2019, to April 8, 2019. A total of 26 usable responses were received.
Bajaj V, Langtry JA. Use of oral glycopyrronium bromide in hyperhidrosis. Br J Dermatol. 2007;157:118-121.
Botox [package insert]. Madison, NJ: Allergan, Inc; 2018.
Strutton DR, Kowalski JW, Glaser DA, et al. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: Results from a national survey. J Am Acad Dermatol. 2004;51:241-248.
Bajaj V, Langtry JA. Use of oral glycopyrronium bromide in hyperhidrosis. Br J Dermatol. 2007;157:118-121.
Botox [package insert]. Madison, NJ: Allergan, Inc; 2018.
Strutton DR, Kowalski JW, Glaser DA, et al. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: Results from a national survey. J Am Acad Dermatol. 2004;51:241-248.
Impact of Spinal Manipulation on Migraine Pain
A recent systematic review and meta-analysis found that spinal manipulation may be an effective therapeutic technique to reduce migraine days and pain intensity. Researchers identified 6 randomized clinical trials (pooled n=677; range of n=42-218) eligible for meta-analysis and evaluated spinal manipulation and migraine-related outcomes through 2017. They found:
- Intervention duration ranged from 2 to 6 months; outcomes included measures of migraine days (primary), migraine pain/intensity, and migraine disability.
- Methodological quality varied across the studies.
- Spinal manipulation reduced migraine days with an overall small effect size, as well as migraine pain/intensity.
Rist PM, Hernandez A, Bernstein C, et al. The impact of spinal manipulation on migraine pain and disability: A systematic review and meta-analysis. Headache. 2019;59(4):532-542. doi:10.1111/head.13501.
A recent systematic review and meta-analysis found that spinal manipulation may be an effective therapeutic technique to reduce migraine days and pain intensity. Researchers identified 6 randomized clinical trials (pooled n=677; range of n=42-218) eligible for meta-analysis and evaluated spinal manipulation and migraine-related outcomes through 2017. They found:
- Intervention duration ranged from 2 to 6 months; outcomes included measures of migraine days (primary), migraine pain/intensity, and migraine disability.
- Methodological quality varied across the studies.
- Spinal manipulation reduced migraine days with an overall small effect size, as well as migraine pain/intensity.
Rist PM, Hernandez A, Bernstein C, et al. The impact of spinal manipulation on migraine pain and disability: A systematic review and meta-analysis. Headache. 2019;59(4):532-542. doi:10.1111/head.13501.
A recent systematic review and meta-analysis found that spinal manipulation may be an effective therapeutic technique to reduce migraine days and pain intensity. Researchers identified 6 randomized clinical trials (pooled n=677; range of n=42-218) eligible for meta-analysis and evaluated spinal manipulation and migraine-related outcomes through 2017. They found:
- Intervention duration ranged from 2 to 6 months; outcomes included measures of migraine days (primary), migraine pain/intensity, and migraine disability.
- Methodological quality varied across the studies.
- Spinal manipulation reduced migraine days with an overall small effect size, as well as migraine pain/intensity.
Rist PM, Hernandez A, Bernstein C, et al. The impact of spinal manipulation on migraine pain and disability: A systematic review and meta-analysis. Headache. 2019;59(4):532-542. doi:10.1111/head.13501.