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Transcatheter aortic valve-in-ring for mitral disease a winner
DENVER – Transseptal mitral valve implantation of an off-the-shelf, commercially available TAVR valve in high-surgical-risk patients with a failing surgically implanted mitral ring prosthesis has become a reasonable treatment strategy in light of the interim findings of the ground-breaking MITRAL trial, Mayra E. Guerrero, MD, said at the Transcatheter Cardiovascular Therapeutics annual educational meeting.
Her presentation of the preliminary results of the MITRAL (Mitral Implantation of Transcatheter Valves) trial showed this valve-in-ring (ViR) treatment strategy using the Sapien 3 valve was associated with low 30-day morbidity and mortality rates and impressive symptomatic improvement.
In contrast, another arm of the MITRAL trial showed that placement of the Sapien 3 TAVR valve in high-surgical-risk patients with severe mitral stenosis due to mitral annular calcification (MAC) of their native valve is a treatment strategy that’s not yet ready for prime time, she added at the meeting, which was sponsored by the Cardiovascular Research Foundation.
“Transcatheter mitral valve replacement in MAC is a challenging procedure associated with complications,” Dr. Guerrero observed. “It may become a reasonable alternative for high-surgical-risk patients with favorable anatomy, but techniques require further refinement.”
The ViR arm of the observational multicenter prospective MITRAL trial included 30 patients with extremely high surgical risk and either severe mitral stenosis as defined by a mitral valve area of 1.5 cm2 or less or moderate mitral stenosis plus severe mitral regurgitation. The most common type of failing ring was the Edwards Physio, in nine patients. Access for transcatheter mitral valve replacement (TMVR) was transseptal in 100% of patients.
The technical success rate at exit from the catheterization lab was 70%. The procedural success rate at 30 days was 62%.
Six patients required a second valve. This was mainly because of malpositioning of the first valve with resultant mitral regurgitation; however, this problem became a nonissue as operator experience grew. All six affected patients were alive at 30 days, and four of the six were New York Heart Association (NYHA) functional class I or II.
In-hospital and 30-day mortality rates were low. There was a single cardiovascular death and one noncardiac death in hospital, with no additional deaths through 30 days. No cases of stroke, acute MI, or valve embolization or thrombosis occurred. The mean mitral valve area at 30 days was 2.1 cm2, although three patients still had a mitral valve area of less 1.5 cm2. Three patients experienced acute renal failure requiring hemodialysis. Seventy-five percent of patients had no or trace mitral regurgitation by echocardiography; the rest had mild regurgitation.
Although at baseline more than 60% of the patients were New York Heart Association class III, 10% were class IV, and the rest were class II, at 30 days more than 30% were New York Heart Association class I, 40% were class II, and the rest were class III.
The 30-day all-cause mortality rate of 6.8% in the MITRAL study is roughly half that reported for ViR patients in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Dr. Guerrero attributed this to refined procedural techniques and improved patient selection through the use of CT imaging and echocardiography.
Heart valve design changes, such as a longer inner skirt, might further improve the technical success rate for ViR, according to Dr. Guerrero, an interventional cardiologist at NorthShore University Health System in Evanston, Ill.
Picking the right ring
Given that studies show one-third of recipients of a surgical mitral ring or surgical mitral valve will require a repeat intervention within 10 years, she made a plea to surgeons: “If we are going to be treating patients with valve-in-ring TMVR, that means when surgeons do a repair they should pick a ring that is amenable to a ViR procedure. So don’t use flexible incomplete bands or very rigid rings because those are really difficult to treat later on. We should pick a ring thinking of the future. That ring is going to fail at some point, and when it fails it’s going to make our lives much easier if we’d picked the right ring.”
MAC TMVR needs more work
In the MAC arm of the MITRAL trial, 96 patients were screened so the researchers could find 30 candidates for TMVR. The 61 rejections were for high risk of left ventricular outflow tract obstruction (LVOTO), embolization, or both.
Fourteen patients underwent transseptal TMVR, and one with anatomy unsuitable for a transseptal procedure had a transapical approach. The other 15 patients had a transatrial surgical approach, which allows resection of the anterior leaflet to reduce the risk of LVOTO and placement of sutures to reduce the embolization risk. However, this came at the cost of increased mortality risk: Three of the five in-hospital deaths were in the transatrial TMVR group.
The technical success rate at exit from the cath lab in the MAC patients was 73%, with a 30-day procedural success rate of 46% and a 19% 30-day mortality. Three patients developed severe LVOTO with hemodynamic compromise.
One transseptal and one transapical TMVR were complicated by LVOTO, both treated by bailout alcohol septal ablation. This led Dr. Guerrero and her coinvestigators to the concept of preemptive alcohol septal ablation, which they used in seven patients deemed at high risk for LVOTO an average of 6 weeks prior to transseptal TMVR as a successful risk reduction strategy.
Survival climbing with operator experience
“In the early days of the TMVR MAC registry, the 30-day mortality rate was 37%. It came down to 22% in the middle third of the registry, then about 18% in the final third. Now we’ve got it down in MITRAL to 16.7%, but when you separate the rate in the transseptal versus the transatrial patients, it’s 13% versus 20%. The difference is not statistically significant, but it’s promising, and I think we are making great progress,” Dr. Guerrero said.
Safety and efficacy endpoints in MITRAL will be reported again at 1 year of follow-up.
The MITRAL trial was partially supported by Edwards Lifesciences. Dr. Guerrero reported receiving a research grant from that company and serving as a consultant to Tendyne Holdings/Abbott and on a speakers bureau for Abiomed.
SOURCE: Guerrero M. No abstract.
DENVER – Transseptal mitral valve implantation of an off-the-shelf, commercially available TAVR valve in high-surgical-risk patients with a failing surgically implanted mitral ring prosthesis has become a reasonable treatment strategy in light of the interim findings of the ground-breaking MITRAL trial, Mayra E. Guerrero, MD, said at the Transcatheter Cardiovascular Therapeutics annual educational meeting.
Her presentation of the preliminary results of the MITRAL (Mitral Implantation of Transcatheter Valves) trial showed this valve-in-ring (ViR) treatment strategy using the Sapien 3 valve was associated with low 30-day morbidity and mortality rates and impressive symptomatic improvement.
In contrast, another arm of the MITRAL trial showed that placement of the Sapien 3 TAVR valve in high-surgical-risk patients with severe mitral stenosis due to mitral annular calcification (MAC) of their native valve is a treatment strategy that’s not yet ready for prime time, she added at the meeting, which was sponsored by the Cardiovascular Research Foundation.
“Transcatheter mitral valve replacement in MAC is a challenging procedure associated with complications,” Dr. Guerrero observed. “It may become a reasonable alternative for high-surgical-risk patients with favorable anatomy, but techniques require further refinement.”
The ViR arm of the observational multicenter prospective MITRAL trial included 30 patients with extremely high surgical risk and either severe mitral stenosis as defined by a mitral valve area of 1.5 cm2 or less or moderate mitral stenosis plus severe mitral regurgitation. The most common type of failing ring was the Edwards Physio, in nine patients. Access for transcatheter mitral valve replacement (TMVR) was transseptal in 100% of patients.
The technical success rate at exit from the catheterization lab was 70%. The procedural success rate at 30 days was 62%.
Six patients required a second valve. This was mainly because of malpositioning of the first valve with resultant mitral regurgitation; however, this problem became a nonissue as operator experience grew. All six affected patients were alive at 30 days, and four of the six were New York Heart Association (NYHA) functional class I or II.
In-hospital and 30-day mortality rates were low. There was a single cardiovascular death and one noncardiac death in hospital, with no additional deaths through 30 days. No cases of stroke, acute MI, or valve embolization or thrombosis occurred. The mean mitral valve area at 30 days was 2.1 cm2, although three patients still had a mitral valve area of less 1.5 cm2. Three patients experienced acute renal failure requiring hemodialysis. Seventy-five percent of patients had no or trace mitral regurgitation by echocardiography; the rest had mild regurgitation.
Although at baseline more than 60% of the patients were New York Heart Association class III, 10% were class IV, and the rest were class II, at 30 days more than 30% were New York Heart Association class I, 40% were class II, and the rest were class III.
The 30-day all-cause mortality rate of 6.8% in the MITRAL study is roughly half that reported for ViR patients in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Dr. Guerrero attributed this to refined procedural techniques and improved patient selection through the use of CT imaging and echocardiography.
Heart valve design changes, such as a longer inner skirt, might further improve the technical success rate for ViR, according to Dr. Guerrero, an interventional cardiologist at NorthShore University Health System in Evanston, Ill.
Picking the right ring
Given that studies show one-third of recipients of a surgical mitral ring or surgical mitral valve will require a repeat intervention within 10 years, she made a plea to surgeons: “If we are going to be treating patients with valve-in-ring TMVR, that means when surgeons do a repair they should pick a ring that is amenable to a ViR procedure. So don’t use flexible incomplete bands or very rigid rings because those are really difficult to treat later on. We should pick a ring thinking of the future. That ring is going to fail at some point, and when it fails it’s going to make our lives much easier if we’d picked the right ring.”
MAC TMVR needs more work
In the MAC arm of the MITRAL trial, 96 patients were screened so the researchers could find 30 candidates for TMVR. The 61 rejections were for high risk of left ventricular outflow tract obstruction (LVOTO), embolization, or both.
Fourteen patients underwent transseptal TMVR, and one with anatomy unsuitable for a transseptal procedure had a transapical approach. The other 15 patients had a transatrial surgical approach, which allows resection of the anterior leaflet to reduce the risk of LVOTO and placement of sutures to reduce the embolization risk. However, this came at the cost of increased mortality risk: Three of the five in-hospital deaths were in the transatrial TMVR group.
The technical success rate at exit from the cath lab in the MAC patients was 73%, with a 30-day procedural success rate of 46% and a 19% 30-day mortality. Three patients developed severe LVOTO with hemodynamic compromise.
One transseptal and one transapical TMVR were complicated by LVOTO, both treated by bailout alcohol septal ablation. This led Dr. Guerrero and her coinvestigators to the concept of preemptive alcohol septal ablation, which they used in seven patients deemed at high risk for LVOTO an average of 6 weeks prior to transseptal TMVR as a successful risk reduction strategy.
Survival climbing with operator experience
“In the early days of the TMVR MAC registry, the 30-day mortality rate was 37%. It came down to 22% in the middle third of the registry, then about 18% in the final third. Now we’ve got it down in MITRAL to 16.7%, but when you separate the rate in the transseptal versus the transatrial patients, it’s 13% versus 20%. The difference is not statistically significant, but it’s promising, and I think we are making great progress,” Dr. Guerrero said.
Safety and efficacy endpoints in MITRAL will be reported again at 1 year of follow-up.
The MITRAL trial was partially supported by Edwards Lifesciences. Dr. Guerrero reported receiving a research grant from that company and serving as a consultant to Tendyne Holdings/Abbott and on a speakers bureau for Abiomed.
SOURCE: Guerrero M. No abstract.
DENVER – Transseptal mitral valve implantation of an off-the-shelf, commercially available TAVR valve in high-surgical-risk patients with a failing surgically implanted mitral ring prosthesis has become a reasonable treatment strategy in light of the interim findings of the ground-breaking MITRAL trial, Mayra E. Guerrero, MD, said at the Transcatheter Cardiovascular Therapeutics annual educational meeting.
Her presentation of the preliminary results of the MITRAL (Mitral Implantation of Transcatheter Valves) trial showed this valve-in-ring (ViR) treatment strategy using the Sapien 3 valve was associated with low 30-day morbidity and mortality rates and impressive symptomatic improvement.
In contrast, another arm of the MITRAL trial showed that placement of the Sapien 3 TAVR valve in high-surgical-risk patients with severe mitral stenosis due to mitral annular calcification (MAC) of their native valve is a treatment strategy that’s not yet ready for prime time, she added at the meeting, which was sponsored by the Cardiovascular Research Foundation.
“Transcatheter mitral valve replacement in MAC is a challenging procedure associated with complications,” Dr. Guerrero observed. “It may become a reasonable alternative for high-surgical-risk patients with favorable anatomy, but techniques require further refinement.”
The ViR arm of the observational multicenter prospective MITRAL trial included 30 patients with extremely high surgical risk and either severe mitral stenosis as defined by a mitral valve area of 1.5 cm2 or less or moderate mitral stenosis plus severe mitral regurgitation. The most common type of failing ring was the Edwards Physio, in nine patients. Access for transcatheter mitral valve replacement (TMVR) was transseptal in 100% of patients.
The technical success rate at exit from the catheterization lab was 70%. The procedural success rate at 30 days was 62%.
Six patients required a second valve. This was mainly because of malpositioning of the first valve with resultant mitral regurgitation; however, this problem became a nonissue as operator experience grew. All six affected patients were alive at 30 days, and four of the six were New York Heart Association (NYHA) functional class I or II.
In-hospital and 30-day mortality rates were low. There was a single cardiovascular death and one noncardiac death in hospital, with no additional deaths through 30 days. No cases of stroke, acute MI, or valve embolization or thrombosis occurred. The mean mitral valve area at 30 days was 2.1 cm2, although three patients still had a mitral valve area of less 1.5 cm2. Three patients experienced acute renal failure requiring hemodialysis. Seventy-five percent of patients had no or trace mitral regurgitation by echocardiography; the rest had mild regurgitation.
Although at baseline more than 60% of the patients were New York Heart Association class III, 10% were class IV, and the rest were class II, at 30 days more than 30% were New York Heart Association class I, 40% were class II, and the rest were class III.
The 30-day all-cause mortality rate of 6.8% in the MITRAL study is roughly half that reported for ViR patients in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Dr. Guerrero attributed this to refined procedural techniques and improved patient selection through the use of CT imaging and echocardiography.
Heart valve design changes, such as a longer inner skirt, might further improve the technical success rate for ViR, according to Dr. Guerrero, an interventional cardiologist at NorthShore University Health System in Evanston, Ill.
Picking the right ring
Given that studies show one-third of recipients of a surgical mitral ring or surgical mitral valve will require a repeat intervention within 10 years, she made a plea to surgeons: “If we are going to be treating patients with valve-in-ring TMVR, that means when surgeons do a repair they should pick a ring that is amenable to a ViR procedure. So don’t use flexible incomplete bands or very rigid rings because those are really difficult to treat later on. We should pick a ring thinking of the future. That ring is going to fail at some point, and when it fails it’s going to make our lives much easier if we’d picked the right ring.”
MAC TMVR needs more work
In the MAC arm of the MITRAL trial, 96 patients were screened so the researchers could find 30 candidates for TMVR. The 61 rejections were for high risk of left ventricular outflow tract obstruction (LVOTO), embolization, or both.
Fourteen patients underwent transseptal TMVR, and one with anatomy unsuitable for a transseptal procedure had a transapical approach. The other 15 patients had a transatrial surgical approach, which allows resection of the anterior leaflet to reduce the risk of LVOTO and placement of sutures to reduce the embolization risk. However, this came at the cost of increased mortality risk: Three of the five in-hospital deaths were in the transatrial TMVR group.
The technical success rate at exit from the cath lab in the MAC patients was 73%, with a 30-day procedural success rate of 46% and a 19% 30-day mortality. Three patients developed severe LVOTO with hemodynamic compromise.
One transseptal and one transapical TMVR were complicated by LVOTO, both treated by bailout alcohol septal ablation. This led Dr. Guerrero and her coinvestigators to the concept of preemptive alcohol septal ablation, which they used in seven patients deemed at high risk for LVOTO an average of 6 weeks prior to transseptal TMVR as a successful risk reduction strategy.
Survival climbing with operator experience
“In the early days of the TMVR MAC registry, the 30-day mortality rate was 37%. It came down to 22% in the middle third of the registry, then about 18% in the final third. Now we’ve got it down in MITRAL to 16.7%, but when you separate the rate in the transseptal versus the transatrial patients, it’s 13% versus 20%. The difference is not statistically significant, but it’s promising, and I think we are making great progress,” Dr. Guerrero said.
Safety and efficacy endpoints in MITRAL will be reported again at 1 year of follow-up.
The MITRAL trial was partially supported by Edwards Lifesciences. Dr. Guerrero reported receiving a research grant from that company and serving as a consultant to Tendyne Holdings/Abbott and on a speakers bureau for Abiomed.
SOURCE: Guerrero M. No abstract.
REPORTING FROM TCT 2017
Key clinical point: .
Major finding: Thirty-day all-cause mortality following a transcatheter valve-in-ring procedure in unacceptably high surgical-risk patients with severe mitral valve disease due to a failing annuloplasty ring was 6.8%.
Study details: This prospective observational study included 60 patients who underwent transcatheter mitral valve replacement for severe mitral valve disease, half due to a failed annuloplasty ring and half secondary to mitral annular calcification.
Disclosures: The MITRAL trial was partially supported by Edwards Lifesciences. The study presenter reported receiving a research grant from the company.
Source: Guerrero M. No abstract.
Atopic dermatitis linked to psychiatric disorders but not hospitalizations
Atopic dermatitis (AD) is associated with anxiety, depression, and suicidal thoughts but does not lead to increased psychiatric hospitalization or suicide, according to a Danish study.
While previous literature has indicated a connection between AD and depressive symptoms, these findings indicated the psychiatric burden is not severe.
A total of 9,656 patients selected from the Danish study of Functional Disorders (DanFunD) during 2011-2015 were asked to fill out a questionnaire concerning clinical diagnoses and psychiatric symptoms.
Investigators also conducted an analysis of 4,259,457 patient records gathered the Danish National Patient Register.
The 1,044 AD patients from the DanFunD were slightly younger on average, at 50 years, compared with an average of 53 years in the 8,612-person control group; there were more women (65%) in the AD group, compared with a relatively even split (53%) in the control group.
Patients with AD were more likely to have clinically diagnosed depression (odds ratio, 1.76) or anxiety (OR, 1.61) than were those in the control group.
The report was published in the journal Allergy.
Among the 568 individuals with symptoms consistent of major depressive disorder, those with AD (112) were almost twice as likely to report these symptoms on the questionnaire (OR, 1.92) and more than twice as likely to report anxiety attacks (OR, 2.32), despite differences in psychiatric hospitalizations remaining insignificant.
The investigators hypothesized the treatment methods for AD patients may be part of the reason that suicide and hospitalization rates were not higher.
“These more severe outcomes of suicide and psychiatric hospitalization could be mitigated in AD patients due to their increased general health care and psychiatric health care utilization leading to, for example, earlier and more aggressive antidepressant therapy,” according to Dr. Thyssen and his fellow investigators.
In an analysis of the general Danish population, medication was most aggressive in patients with moderate-severe AD, who were significantly more likely to use antidepressants (hazard ratio,1.24) and anxiolytic drugs (HR, 1.66), while those with milder symptoms had only a slightly increased likelihood.
Because of the observational nature of the study, investigators could not determine what the specific cause of these psychiatric symptoms were.
The DanFunD Study was supported by TrygFonden and Lundbeck Foundation. Dr. Thyssen is supported by a grant from the Lundbeck Foundation. Some of the investigators received financial support from various pharmaceutical companies or their foundations. The remaining investigators reported no relevant financial disclosures.
SOURCE: Thyssen JP et al. Allergy. 2018 Jan;73(1):214-20.
Atopic dermatitis (AD) is associated with anxiety, depression, and suicidal thoughts but does not lead to increased psychiatric hospitalization or suicide, according to a Danish study.
While previous literature has indicated a connection between AD and depressive symptoms, these findings indicated the psychiatric burden is not severe.
A total of 9,656 patients selected from the Danish study of Functional Disorders (DanFunD) during 2011-2015 were asked to fill out a questionnaire concerning clinical diagnoses and psychiatric symptoms.
Investigators also conducted an analysis of 4,259,457 patient records gathered the Danish National Patient Register.
The 1,044 AD patients from the DanFunD were slightly younger on average, at 50 years, compared with an average of 53 years in the 8,612-person control group; there were more women (65%) in the AD group, compared with a relatively even split (53%) in the control group.
Patients with AD were more likely to have clinically diagnosed depression (odds ratio, 1.76) or anxiety (OR, 1.61) than were those in the control group.
The report was published in the journal Allergy.
Among the 568 individuals with symptoms consistent of major depressive disorder, those with AD (112) were almost twice as likely to report these symptoms on the questionnaire (OR, 1.92) and more than twice as likely to report anxiety attacks (OR, 2.32), despite differences in psychiatric hospitalizations remaining insignificant.
The investigators hypothesized the treatment methods for AD patients may be part of the reason that suicide and hospitalization rates were not higher.
“These more severe outcomes of suicide and psychiatric hospitalization could be mitigated in AD patients due to their increased general health care and psychiatric health care utilization leading to, for example, earlier and more aggressive antidepressant therapy,” according to Dr. Thyssen and his fellow investigators.
In an analysis of the general Danish population, medication was most aggressive in patients with moderate-severe AD, who were significantly more likely to use antidepressants (hazard ratio,1.24) and anxiolytic drugs (HR, 1.66), while those with milder symptoms had only a slightly increased likelihood.
Because of the observational nature of the study, investigators could not determine what the specific cause of these psychiatric symptoms were.
The DanFunD Study was supported by TrygFonden and Lundbeck Foundation. Dr. Thyssen is supported by a grant from the Lundbeck Foundation. Some of the investigators received financial support from various pharmaceutical companies or their foundations. The remaining investigators reported no relevant financial disclosures.
SOURCE: Thyssen JP et al. Allergy. 2018 Jan;73(1):214-20.
Atopic dermatitis (AD) is associated with anxiety, depression, and suicidal thoughts but does not lead to increased psychiatric hospitalization or suicide, according to a Danish study.
While previous literature has indicated a connection between AD and depressive symptoms, these findings indicated the psychiatric burden is not severe.
A total of 9,656 patients selected from the Danish study of Functional Disorders (DanFunD) during 2011-2015 were asked to fill out a questionnaire concerning clinical diagnoses and psychiatric symptoms.
Investigators also conducted an analysis of 4,259,457 patient records gathered the Danish National Patient Register.
The 1,044 AD patients from the DanFunD were slightly younger on average, at 50 years, compared with an average of 53 years in the 8,612-person control group; there were more women (65%) in the AD group, compared with a relatively even split (53%) in the control group.
Patients with AD were more likely to have clinically diagnosed depression (odds ratio, 1.76) or anxiety (OR, 1.61) than were those in the control group.
The report was published in the journal Allergy.
Among the 568 individuals with symptoms consistent of major depressive disorder, those with AD (112) were almost twice as likely to report these symptoms on the questionnaire (OR, 1.92) and more than twice as likely to report anxiety attacks (OR, 2.32), despite differences in psychiatric hospitalizations remaining insignificant.
The investigators hypothesized the treatment methods for AD patients may be part of the reason that suicide and hospitalization rates were not higher.
“These more severe outcomes of suicide and psychiatric hospitalization could be mitigated in AD patients due to their increased general health care and psychiatric health care utilization leading to, for example, earlier and more aggressive antidepressant therapy,” according to Dr. Thyssen and his fellow investigators.
In an analysis of the general Danish population, medication was most aggressive in patients with moderate-severe AD, who were significantly more likely to use antidepressants (hazard ratio,1.24) and anxiolytic drugs (HR, 1.66), while those with milder symptoms had only a slightly increased likelihood.
Because of the observational nature of the study, investigators could not determine what the specific cause of these psychiatric symptoms were.
The DanFunD Study was supported by TrygFonden and Lundbeck Foundation. Dr. Thyssen is supported by a grant from the Lundbeck Foundation. Some of the investigators received financial support from various pharmaceutical companies or their foundations. The remaining investigators reported no relevant financial disclosures.
SOURCE: Thyssen JP et al. Allergy. 2018 Jan;73(1):214-20.
FROM ALLERGY
Key clinical point:
Major finding: Atopic dermatitis patients were at greater risk for depression (OR, 1.76) and anxiety (OR, 1.61).
Study details: Observational, controlled study of 9,656 Danish residents collected from the Danish study of Functional Disorders between 2011 and 2015, and an analysis of 4,259,457 patient records gathered the Danish National Patient Register.
Disclosures: The DanFunD Study was supported by TrygFonden and Lundbeck Foundation. Dr. Thyssen is supported by a grant from the Lundbeck Foundation. Some of the investigators received financial support from various pharmaceutical companies or their foundations. The remaining investigators reported no relevant financial disclosures.
Source: Thyssen JP et al. Allergy. 2018 Jan;73(1):214-20.
Pendulum swings on mesenteric venous thrombosis treatment
CHICAGO – Treatment of isolated acute mesenteric venous thrombosis remains a topic of controversy, with no established guidelines available, Thomas S. Maldonado, MD, observed at a symposium on vascular surgery sponsored by Northwestern University.
“There has been a pendulum swing. Earlier on there was a lot of excitement about surgical thrombectomy, then we tended to become more nonoperative and conservative, using just anticoagulation. But in recent years endovascular therapy has been gaining some traction and shows good preliminary results,” according to Dr. Maldonado, professor of surgery at New York University.
Today MVT accounts for 1 in 1,000 emergency department visits and 6%-9% of cases of acute mesenteric ischemia. Dr. Maldonado cited two reasons for the increasing incidence. One is the widespread recognition that contrast-enhanced helical CT is the diagnostic imaging method of choice; it is being employed more liberally because of its ready availability and overall 95%-100% accuracy, which allows for rapid and reliable diagnosis with precise location of the thrombus.
The other factor is that bariatric surgery is booming. While the most common local etiologies of the hypercoagulable state predisposing to MVT remain cancer and intra-abdominal inflammatory diseases such as pancreatitis, there is no doubt that laparoscopic bariatric surgery is emerging as another contributing factor, according to the surgeon.
Diagnosis
MVT is an insidious and lethal disease. In most series, it has a mortality of at least 25%, and it doesn’t appear to be going down in recent years. This is probably because of difficulty in making a prompt diagnosis before bowel ischemia occurs. Multiple studies show that onset of symptoms typically occurs 6-14 days before patients present for care.
“I think this is really the Achilles heel of this diagnosis – that it can be delayed. The diagnosis can be elusive. There is no constellation of signs or symptoms that is pathognomonic for MVT. This is where prompt recognition and a CT scan can really play an important role,” Dr. Maldonado said.
He and a coworker conducted a review of 37 studies on MVT published in 1997-2016 which underscored the challenges in making a prompt diagnosis. The most common presenting symptom was nonspecific abdominal pain out of proportion to findings on physical exam. Other possible symptoms included anorexia, nausea, vomiting, constipation, and/or passage of blood through the anus. The disease occurred most often in men aged 40-60. A history of unprovoked venous thromboembolism was often present (J Vasc Surg Venous Lymphat Disord. 2016 Oct;4[4]:501-7).
The three-phase CT scan – arterial, venous, and delayed venous – not only locates the thrombus with precision, it also shows whether the occlusion is partial or complete, which is important information prognostically (see below). The scan also provides information on bowel ischemia with at least 90% sensitivity and specificity. Bowel compromise shows up on CT as a thickened bowel wall with dilated lumen, mesenteric fat stranding, and ascites.
CT imaging has become so useful for rapid diagnosis of MVT that duplex ultrasound, although considerably less costly and radiation-free, has become relegated to a secondary role. At most centers its use is restricted to follow-up surveillance to assess for thrombus resolution and vascular recanalization after the acute episode has been treated. Duplex ultrasound simply can’t match CT in the crucial task of assessment for bowel ischemia.
Treatment
The mainstay of treatment in patients with MVT without bowel ischemia is medical management: immediate anticoagulation with unfractionated or low-molecular-weight heparin bridging to warfarin, bowel rest, aggressive fluid resuscitation, and correction of electrolyte imbalances. Most patients with nonocclusive MVT and no ischemic bowel can be managed in this way without surgical intervention. The newer oral anticoagulants haven’t yet been studied in patients with MVT.
How long to continue oral anticoagulation is an unresolved issue. In Dr. Maldonado’s literature review, the median duration was 90 days. In his own practice, anticoagulants aren’t stopped until duplex ultrasound demonstrates recanalization of the mesenteric venous system. If residual thrombus is present or a patient has an underlying hypercoagulable state, treatment continues indefinitely.
In a series of 50 noncirrhotic MVT patients treated at New York University using various strategies, 19, or 38%, were completely recanalized. Recurrence of MVT after successful treatment occurred in only 2 of these 19 patients, in both cases upon discontinuation of anticoagulation.
“It speaks to the issue of length of treatment – or should it be discontinued at all?” the surgeon said.
Open surgical thrombectomy has fallen into disfavor because the thrombus tends to recur within 7 days post surgery. It is now best reserved for patients with acute MVT with a contraindication to thrombolytic therapy, such as cirrhosis or recent major surgery, according to Dr. Maldonado.
Multiple patient series using endovascular catheter-directed thrombolytic therapy with a transhepatic, transvenous, transarterial, or combined approach have reported high rates of successful recanalization – even in the 90% range – with low recurrence rates and fewer bowel resections than with anticoagulation alone.
Indeed, Dr. Maldonado and his fellow vascular surgeons at New York University have recently developed a management algorithm whereby patients with occlusive MVT and no bowel ischemia undergo catheter-directed thrombolysis provided there are no contraindications, such as uncontrolled hypertension or a recent hemorrhagic stroke. The surgeons will also seriously consider catheter-directed lytic therapy in MVT patients with bowel ischemia who show no improvement after laparotomy, bowel resection, and open thrombectomy.
Prognosis
A retrospective review by Dr. Maldonado and coinvestigators of 80 noncirrhotic patients with MVT managed at New York University raised a red flag regarding the high risk of portal hypertension as a long-term sequela. At a median follow-up of 480 days, fully half of patients with imaging results available displayed radiographic features of portal hypertension, although as yet none had developed frank clinical manifestations of cirrhosis.
The investigators identified two predictors of portal hypertension. One was complete as opposed to partial thrombosis at the initial event. Complete thrombosis was present in 73% of patients who eventually developed portal hypertension, compared with 43% of those who didn’t. The other predictor was lack of successful recanalization: only 37% of patients who developed portal hypertension were successfully recanalized, compared with a 65% recanalization rate in those who remained free of this long-term complication (J Vasc Surg Venous Lymphat Disord. 2016 Oct;4[4]:400-6).
These observations raise the possibility that initial complete thrombosis of the mesenteric vein and nonrecanalization with medical therapy might tip the balance in favor of endovascular lytic therapy as a potential means of preventing later portal hypertension.
“I don’t think we know the answer, but there’s certainly room for research,” Dr. Maldonado observed.
He reported having no financial conflicts regarding his presentation.
CHICAGO – Treatment of isolated acute mesenteric venous thrombosis remains a topic of controversy, with no established guidelines available, Thomas S. Maldonado, MD, observed at a symposium on vascular surgery sponsored by Northwestern University.
“There has been a pendulum swing. Earlier on there was a lot of excitement about surgical thrombectomy, then we tended to become more nonoperative and conservative, using just anticoagulation. But in recent years endovascular therapy has been gaining some traction and shows good preliminary results,” according to Dr. Maldonado, professor of surgery at New York University.
Today MVT accounts for 1 in 1,000 emergency department visits and 6%-9% of cases of acute mesenteric ischemia. Dr. Maldonado cited two reasons for the increasing incidence. One is the widespread recognition that contrast-enhanced helical CT is the diagnostic imaging method of choice; it is being employed more liberally because of its ready availability and overall 95%-100% accuracy, which allows for rapid and reliable diagnosis with precise location of the thrombus.
The other factor is that bariatric surgery is booming. While the most common local etiologies of the hypercoagulable state predisposing to MVT remain cancer and intra-abdominal inflammatory diseases such as pancreatitis, there is no doubt that laparoscopic bariatric surgery is emerging as another contributing factor, according to the surgeon.
Diagnosis
MVT is an insidious and lethal disease. In most series, it has a mortality of at least 25%, and it doesn’t appear to be going down in recent years. This is probably because of difficulty in making a prompt diagnosis before bowel ischemia occurs. Multiple studies show that onset of symptoms typically occurs 6-14 days before patients present for care.
“I think this is really the Achilles heel of this diagnosis – that it can be delayed. The diagnosis can be elusive. There is no constellation of signs or symptoms that is pathognomonic for MVT. This is where prompt recognition and a CT scan can really play an important role,” Dr. Maldonado said.
He and a coworker conducted a review of 37 studies on MVT published in 1997-2016 which underscored the challenges in making a prompt diagnosis. The most common presenting symptom was nonspecific abdominal pain out of proportion to findings on physical exam. Other possible symptoms included anorexia, nausea, vomiting, constipation, and/or passage of blood through the anus. The disease occurred most often in men aged 40-60. A history of unprovoked venous thromboembolism was often present (J Vasc Surg Venous Lymphat Disord. 2016 Oct;4[4]:501-7).
The three-phase CT scan – arterial, venous, and delayed venous – not only locates the thrombus with precision, it also shows whether the occlusion is partial or complete, which is important information prognostically (see below). The scan also provides information on bowel ischemia with at least 90% sensitivity and specificity. Bowel compromise shows up on CT as a thickened bowel wall with dilated lumen, mesenteric fat stranding, and ascites.
CT imaging has become so useful for rapid diagnosis of MVT that duplex ultrasound, although considerably less costly and radiation-free, has become relegated to a secondary role. At most centers its use is restricted to follow-up surveillance to assess for thrombus resolution and vascular recanalization after the acute episode has been treated. Duplex ultrasound simply can’t match CT in the crucial task of assessment for bowel ischemia.
Treatment
The mainstay of treatment in patients with MVT without bowel ischemia is medical management: immediate anticoagulation with unfractionated or low-molecular-weight heparin bridging to warfarin, bowel rest, aggressive fluid resuscitation, and correction of electrolyte imbalances. Most patients with nonocclusive MVT and no ischemic bowel can be managed in this way without surgical intervention. The newer oral anticoagulants haven’t yet been studied in patients with MVT.
How long to continue oral anticoagulation is an unresolved issue. In Dr. Maldonado’s literature review, the median duration was 90 days. In his own practice, anticoagulants aren’t stopped until duplex ultrasound demonstrates recanalization of the mesenteric venous system. If residual thrombus is present or a patient has an underlying hypercoagulable state, treatment continues indefinitely.
In a series of 50 noncirrhotic MVT patients treated at New York University using various strategies, 19, or 38%, were completely recanalized. Recurrence of MVT after successful treatment occurred in only 2 of these 19 patients, in both cases upon discontinuation of anticoagulation.
“It speaks to the issue of length of treatment – or should it be discontinued at all?” the surgeon said.
Open surgical thrombectomy has fallen into disfavor because the thrombus tends to recur within 7 days post surgery. It is now best reserved for patients with acute MVT with a contraindication to thrombolytic therapy, such as cirrhosis or recent major surgery, according to Dr. Maldonado.
Multiple patient series using endovascular catheter-directed thrombolytic therapy with a transhepatic, transvenous, transarterial, or combined approach have reported high rates of successful recanalization – even in the 90% range – with low recurrence rates and fewer bowel resections than with anticoagulation alone.
Indeed, Dr. Maldonado and his fellow vascular surgeons at New York University have recently developed a management algorithm whereby patients with occlusive MVT and no bowel ischemia undergo catheter-directed thrombolysis provided there are no contraindications, such as uncontrolled hypertension or a recent hemorrhagic stroke. The surgeons will also seriously consider catheter-directed lytic therapy in MVT patients with bowel ischemia who show no improvement after laparotomy, bowel resection, and open thrombectomy.
Prognosis
A retrospective review by Dr. Maldonado and coinvestigators of 80 noncirrhotic patients with MVT managed at New York University raised a red flag regarding the high risk of portal hypertension as a long-term sequela. At a median follow-up of 480 days, fully half of patients with imaging results available displayed radiographic features of portal hypertension, although as yet none had developed frank clinical manifestations of cirrhosis.
The investigators identified two predictors of portal hypertension. One was complete as opposed to partial thrombosis at the initial event. Complete thrombosis was present in 73% of patients who eventually developed portal hypertension, compared with 43% of those who didn’t. The other predictor was lack of successful recanalization: only 37% of patients who developed portal hypertension were successfully recanalized, compared with a 65% recanalization rate in those who remained free of this long-term complication (J Vasc Surg Venous Lymphat Disord. 2016 Oct;4[4]:400-6).
These observations raise the possibility that initial complete thrombosis of the mesenteric vein and nonrecanalization with medical therapy might tip the balance in favor of endovascular lytic therapy as a potential means of preventing later portal hypertension.
“I don’t think we know the answer, but there’s certainly room for research,” Dr. Maldonado observed.
He reported having no financial conflicts regarding his presentation.
CHICAGO – Treatment of isolated acute mesenteric venous thrombosis remains a topic of controversy, with no established guidelines available, Thomas S. Maldonado, MD, observed at a symposium on vascular surgery sponsored by Northwestern University.
“There has been a pendulum swing. Earlier on there was a lot of excitement about surgical thrombectomy, then we tended to become more nonoperative and conservative, using just anticoagulation. But in recent years endovascular therapy has been gaining some traction and shows good preliminary results,” according to Dr. Maldonado, professor of surgery at New York University.
Today MVT accounts for 1 in 1,000 emergency department visits and 6%-9% of cases of acute mesenteric ischemia. Dr. Maldonado cited two reasons for the increasing incidence. One is the widespread recognition that contrast-enhanced helical CT is the diagnostic imaging method of choice; it is being employed more liberally because of its ready availability and overall 95%-100% accuracy, which allows for rapid and reliable diagnosis with precise location of the thrombus.
The other factor is that bariatric surgery is booming. While the most common local etiologies of the hypercoagulable state predisposing to MVT remain cancer and intra-abdominal inflammatory diseases such as pancreatitis, there is no doubt that laparoscopic bariatric surgery is emerging as another contributing factor, according to the surgeon.
Diagnosis
MVT is an insidious and lethal disease. In most series, it has a mortality of at least 25%, and it doesn’t appear to be going down in recent years. This is probably because of difficulty in making a prompt diagnosis before bowel ischemia occurs. Multiple studies show that onset of symptoms typically occurs 6-14 days before patients present for care.
“I think this is really the Achilles heel of this diagnosis – that it can be delayed. The diagnosis can be elusive. There is no constellation of signs or symptoms that is pathognomonic for MVT. This is where prompt recognition and a CT scan can really play an important role,” Dr. Maldonado said.
He and a coworker conducted a review of 37 studies on MVT published in 1997-2016 which underscored the challenges in making a prompt diagnosis. The most common presenting symptom was nonspecific abdominal pain out of proportion to findings on physical exam. Other possible symptoms included anorexia, nausea, vomiting, constipation, and/or passage of blood through the anus. The disease occurred most often in men aged 40-60. A history of unprovoked venous thromboembolism was often present (J Vasc Surg Venous Lymphat Disord. 2016 Oct;4[4]:501-7).
The three-phase CT scan – arterial, venous, and delayed venous – not only locates the thrombus with precision, it also shows whether the occlusion is partial or complete, which is important information prognostically (see below). The scan also provides information on bowel ischemia with at least 90% sensitivity and specificity. Bowel compromise shows up on CT as a thickened bowel wall with dilated lumen, mesenteric fat stranding, and ascites.
CT imaging has become so useful for rapid diagnosis of MVT that duplex ultrasound, although considerably less costly and radiation-free, has become relegated to a secondary role. At most centers its use is restricted to follow-up surveillance to assess for thrombus resolution and vascular recanalization after the acute episode has been treated. Duplex ultrasound simply can’t match CT in the crucial task of assessment for bowel ischemia.
Treatment
The mainstay of treatment in patients with MVT without bowel ischemia is medical management: immediate anticoagulation with unfractionated or low-molecular-weight heparin bridging to warfarin, bowel rest, aggressive fluid resuscitation, and correction of electrolyte imbalances. Most patients with nonocclusive MVT and no ischemic bowel can be managed in this way without surgical intervention. The newer oral anticoagulants haven’t yet been studied in patients with MVT.
How long to continue oral anticoagulation is an unresolved issue. In Dr. Maldonado’s literature review, the median duration was 90 days. In his own practice, anticoagulants aren’t stopped until duplex ultrasound demonstrates recanalization of the mesenteric venous system. If residual thrombus is present or a patient has an underlying hypercoagulable state, treatment continues indefinitely.
In a series of 50 noncirrhotic MVT patients treated at New York University using various strategies, 19, or 38%, were completely recanalized. Recurrence of MVT after successful treatment occurred in only 2 of these 19 patients, in both cases upon discontinuation of anticoagulation.
“It speaks to the issue of length of treatment – or should it be discontinued at all?” the surgeon said.
Open surgical thrombectomy has fallen into disfavor because the thrombus tends to recur within 7 days post surgery. It is now best reserved for patients with acute MVT with a contraindication to thrombolytic therapy, such as cirrhosis or recent major surgery, according to Dr. Maldonado.
Multiple patient series using endovascular catheter-directed thrombolytic therapy with a transhepatic, transvenous, transarterial, or combined approach have reported high rates of successful recanalization – even in the 90% range – with low recurrence rates and fewer bowel resections than with anticoagulation alone.
Indeed, Dr. Maldonado and his fellow vascular surgeons at New York University have recently developed a management algorithm whereby patients with occlusive MVT and no bowel ischemia undergo catheter-directed thrombolysis provided there are no contraindications, such as uncontrolled hypertension or a recent hemorrhagic stroke. The surgeons will also seriously consider catheter-directed lytic therapy in MVT patients with bowel ischemia who show no improvement after laparotomy, bowel resection, and open thrombectomy.
Prognosis
A retrospective review by Dr. Maldonado and coinvestigators of 80 noncirrhotic patients with MVT managed at New York University raised a red flag regarding the high risk of portal hypertension as a long-term sequela. At a median follow-up of 480 days, fully half of patients with imaging results available displayed radiographic features of portal hypertension, although as yet none had developed frank clinical manifestations of cirrhosis.
The investigators identified two predictors of portal hypertension. One was complete as opposed to partial thrombosis at the initial event. Complete thrombosis was present in 73% of patients who eventually developed portal hypertension, compared with 43% of those who didn’t. The other predictor was lack of successful recanalization: only 37% of patients who developed portal hypertension were successfully recanalized, compared with a 65% recanalization rate in those who remained free of this long-term complication (J Vasc Surg Venous Lymphat Disord. 2016 Oct;4[4]:400-6).
These observations raise the possibility that initial complete thrombosis of the mesenteric vein and nonrecanalization with medical therapy might tip the balance in favor of endovascular lytic therapy as a potential means of preventing later portal hypertension.
“I don’t think we know the answer, but there’s certainly room for research,” Dr. Maldonado observed.
He reported having no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM
NIOSH Survey: Adherence to Best Practices is Falling Short
The health care industry sees more nonfatal occupational injury and illness than other industry sectors. One reason may be that employers and employees are not adhering to health and safety best practices, according to a recent National Institute for Occupational Safety and Health (NIOSH) survey of nearly 11,000 workers in a wide range of professional, technical, and support occupations.
The survey—the largest federally sponsored survey addressing chemical hazards in health care—found lapses everywhere. For instance, when administering aerosolized pentamidine, 69% of health care workers did not always wear protective gowns, 49% did not always wear respiratory protection, and 22% did not always wear protective gloves.
When NIOSH compared responses from respondents who administered pentamidine versus those who administered antibiotics, it found that those who administered pentamidine were more likely to be trained, familiar with employer standard procedures, and use eye/face protection and respirators. The major barrier to using personal protective equipment for those who administered either pentamidine or antibiotics include “the perception that aerosolized medications are not as dangerous as other chemicals.” Moreover, NIOSH concluded that there was “a belief” that employers do not fully appreciate the potential adverse health effects associated with exposure to the drugs, and thus do not prioritize adherence.
The survey also revealed that best practices to minimize exposure to high-level disinfectants are not universally implemented: 17% of respondents said they never received training. Of those who received training, 42% said it was > 12 months before, and 19% said employer safe handling procedures were unavailable. Nearly half of respondents did not always wear a protective gown when handling the products; 9% did not always wear protective gloves.
Among other findings: use of anesthesia machines with scavenging systems was “nearly universal.” However, adherence to other best practices was lacking. For instance, one third of health care workers who administered anesthetic gases to children and 14% of those with adult patients started the anesthetic gas flow before the delivery mask or airway mask was applied to the patient. And, 18% of respondents said they never received training. Of those who did receive training, 81% said it had been > 12 months before. Not surprisingly, NIOSH concludes that findings from the survey show that best practices have not been implemented and adherence is “not universal.”
The health care industry sees more nonfatal occupational injury and illness than other industry sectors. One reason may be that employers and employees are not adhering to health and safety best practices, according to a recent National Institute for Occupational Safety and Health (NIOSH) survey of nearly 11,000 workers in a wide range of professional, technical, and support occupations.
The survey—the largest federally sponsored survey addressing chemical hazards in health care—found lapses everywhere. For instance, when administering aerosolized pentamidine, 69% of health care workers did not always wear protective gowns, 49% did not always wear respiratory protection, and 22% did not always wear protective gloves.
When NIOSH compared responses from respondents who administered pentamidine versus those who administered antibiotics, it found that those who administered pentamidine were more likely to be trained, familiar with employer standard procedures, and use eye/face protection and respirators. The major barrier to using personal protective equipment for those who administered either pentamidine or antibiotics include “the perception that aerosolized medications are not as dangerous as other chemicals.” Moreover, NIOSH concluded that there was “a belief” that employers do not fully appreciate the potential adverse health effects associated with exposure to the drugs, and thus do not prioritize adherence.
The survey also revealed that best practices to minimize exposure to high-level disinfectants are not universally implemented: 17% of respondents said they never received training. Of those who received training, 42% said it was > 12 months before, and 19% said employer safe handling procedures were unavailable. Nearly half of respondents did not always wear a protective gown when handling the products; 9% did not always wear protective gloves.
Among other findings: use of anesthesia machines with scavenging systems was “nearly universal.” However, adherence to other best practices was lacking. For instance, one third of health care workers who administered anesthetic gases to children and 14% of those with adult patients started the anesthetic gas flow before the delivery mask or airway mask was applied to the patient. And, 18% of respondents said they never received training. Of those who did receive training, 81% said it had been > 12 months before. Not surprisingly, NIOSH concludes that findings from the survey show that best practices have not been implemented and adherence is “not universal.”
The health care industry sees more nonfatal occupational injury and illness than other industry sectors. One reason may be that employers and employees are not adhering to health and safety best practices, according to a recent National Institute for Occupational Safety and Health (NIOSH) survey of nearly 11,000 workers in a wide range of professional, technical, and support occupations.
The survey—the largest federally sponsored survey addressing chemical hazards in health care—found lapses everywhere. For instance, when administering aerosolized pentamidine, 69% of health care workers did not always wear protective gowns, 49% did not always wear respiratory protection, and 22% did not always wear protective gloves.
When NIOSH compared responses from respondents who administered pentamidine versus those who administered antibiotics, it found that those who administered pentamidine were more likely to be trained, familiar with employer standard procedures, and use eye/face protection and respirators. The major barrier to using personal protective equipment for those who administered either pentamidine or antibiotics include “the perception that aerosolized medications are not as dangerous as other chemicals.” Moreover, NIOSH concluded that there was “a belief” that employers do not fully appreciate the potential adverse health effects associated with exposure to the drugs, and thus do not prioritize adherence.
The survey also revealed that best practices to minimize exposure to high-level disinfectants are not universally implemented: 17% of respondents said they never received training. Of those who received training, 42% said it was > 12 months before, and 19% said employer safe handling procedures were unavailable. Nearly half of respondents did not always wear a protective gown when handling the products; 9% did not always wear protective gloves.
Among other findings: use of anesthesia machines with scavenging systems was “nearly universal.” However, adherence to other best practices was lacking. For instance, one third of health care workers who administered anesthetic gases to children and 14% of those with adult patients started the anesthetic gas flow before the delivery mask or airway mask was applied to the patient. And, 18% of respondents said they never received training. Of those who did receive training, 81% said it had been > 12 months before. Not surprisingly, NIOSH concludes that findings from the survey show that best practices have not been implemented and adherence is “not universal.”
Can Albumin/Globulin Levels Predict Digestive Cancer Prognosis?
Does the albumin/globulin ratio (AGR) predict prognosis in digestive system cancers? No convincing conclusions have been made, say researchers from Nan Chang University in China. They conducted a meta-analysis of 15 studies involving nearly 10,000 patients. The results indicated that a low pretreatment AGR was significantly related to worse survival outcomes for patients with colorectal and other cancers of the digestive system.
Of the analyzed studies, 13 explored the association of AGR with overall survival and found that a low AGR nearly doubled the risk of death. When the researchers adjusted for cancer type, region, sample size, treatment method, and other variables, a low AGR remained a predictor for worse overall survival in colorectal, esophageal, and gastric cancer; hazard ratios (HR) equal to 2.39, 1.35, and 1.56, respectively. Two studies explored the association of a low AGR with cancer-specific survival; again a low AGR was significantly related to worse outcome (HR = 1.61).
The researchers say effects of nutrition and inflammation may underlie the prognostic value of the AGR. They refer to the “mutual promotion effect” between cancer progression and inflammation, and to the fact that cancer patients are vulnerable to cachexia, which also contributes to tumor growth. Moreover, serum albumin reflects not only the body’s nutritional status, but also, according to recent research, the inflammatory status. The serum globulin level is closely associated with immune and inflammatory status and is easily affected by dehydration and fluid retention, common to cancer patients.
Thus, the AGR, which accounts for both levels concurrently, may mirror nutritional and inflammatory indexes more precisely, the researchers say, and could be a helpful biomarker.
Source:
Guo HW, Yuan TZ, Chen JX, Zheng Y. PLoS One. 2018;13(1):e0189839.
doi: 10.1371/journal.pone.0189839.
Does the albumin/globulin ratio (AGR) predict prognosis in digestive system cancers? No convincing conclusions have been made, say researchers from Nan Chang University in China. They conducted a meta-analysis of 15 studies involving nearly 10,000 patients. The results indicated that a low pretreatment AGR was significantly related to worse survival outcomes for patients with colorectal and other cancers of the digestive system.
Of the analyzed studies, 13 explored the association of AGR with overall survival and found that a low AGR nearly doubled the risk of death. When the researchers adjusted for cancer type, region, sample size, treatment method, and other variables, a low AGR remained a predictor for worse overall survival in colorectal, esophageal, and gastric cancer; hazard ratios (HR) equal to 2.39, 1.35, and 1.56, respectively. Two studies explored the association of a low AGR with cancer-specific survival; again a low AGR was significantly related to worse outcome (HR = 1.61).
The researchers say effects of nutrition and inflammation may underlie the prognostic value of the AGR. They refer to the “mutual promotion effect” between cancer progression and inflammation, and to the fact that cancer patients are vulnerable to cachexia, which also contributes to tumor growth. Moreover, serum albumin reflects not only the body’s nutritional status, but also, according to recent research, the inflammatory status. The serum globulin level is closely associated with immune and inflammatory status and is easily affected by dehydration and fluid retention, common to cancer patients.
Thus, the AGR, which accounts for both levels concurrently, may mirror nutritional and inflammatory indexes more precisely, the researchers say, and could be a helpful biomarker.
Source:
Guo HW, Yuan TZ, Chen JX, Zheng Y. PLoS One. 2018;13(1):e0189839.
doi: 10.1371/journal.pone.0189839.
Does the albumin/globulin ratio (AGR) predict prognosis in digestive system cancers? No convincing conclusions have been made, say researchers from Nan Chang University in China. They conducted a meta-analysis of 15 studies involving nearly 10,000 patients. The results indicated that a low pretreatment AGR was significantly related to worse survival outcomes for patients with colorectal and other cancers of the digestive system.
Of the analyzed studies, 13 explored the association of AGR with overall survival and found that a low AGR nearly doubled the risk of death. When the researchers adjusted for cancer type, region, sample size, treatment method, and other variables, a low AGR remained a predictor for worse overall survival in colorectal, esophageal, and gastric cancer; hazard ratios (HR) equal to 2.39, 1.35, and 1.56, respectively. Two studies explored the association of a low AGR with cancer-specific survival; again a low AGR was significantly related to worse outcome (HR = 1.61).
The researchers say effects of nutrition and inflammation may underlie the prognostic value of the AGR. They refer to the “mutual promotion effect” between cancer progression and inflammation, and to the fact that cancer patients are vulnerable to cachexia, which also contributes to tumor growth. Moreover, serum albumin reflects not only the body’s nutritional status, but also, according to recent research, the inflammatory status. The serum globulin level is closely associated with immune and inflammatory status and is easily affected by dehydration and fluid retention, common to cancer patients.
Thus, the AGR, which accounts for both levels concurrently, may mirror nutritional and inflammatory indexes more precisely, the researchers say, and could be a helpful biomarker.
Source:
Guo HW, Yuan TZ, Chen JX, Zheng Y. PLoS One. 2018;13(1):e0189839.
doi: 10.1371/journal.pone.0189839.
Risks of MGUS persist beyond 30 years
A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.
The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.
Patients with MGUS also had a significantly shorter median survival than controls.
Researchers reported these findings in NEJM.
“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.
“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”
With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.
The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.
During that time, 147 patients progressed to another disorder, including:
- 97 to multiple myeloma
- 19 to non-Hodgkin lymphoma
- 14 to AL amyloidosis
- 13 to Waldenstrom’s macroglobulinemia
- 3 to chronic lymphocytic leukemia
- 1 to plasmacytoma.
The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.
The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.
“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.
The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).
Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed. 
A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.
The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.
Patients with MGUS also had a significantly shorter median survival than controls.
Researchers reported these findings in NEJM.
“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.
“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”
With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.
The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.
During that time, 147 patients progressed to another disorder, including:
- 97 to multiple myeloma
- 19 to non-Hodgkin lymphoma
- 14 to AL amyloidosis
- 13 to Waldenstrom’s macroglobulinemia
- 3 to chronic lymphocytic leukemia
- 1 to plasmacytoma.
The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.
The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.
“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.
The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).
Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed.
A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.
The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.
Patients with MGUS also had a significantly shorter median survival than controls.
Researchers reported these findings in NEJM.
“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.
“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”
With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.
The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.
During that time, 147 patients progressed to another disorder, including:
- 97 to multiple myeloma
- 19 to non-Hodgkin lymphoma
- 14 to AL amyloidosis
- 13 to Waldenstrom’s macroglobulinemia
- 3 to chronic lymphocytic leukemia
- 1 to plasmacytoma.
The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.
The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.
“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.
The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).
Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed.
CAR T-cell therapy on fast track in US, EU
The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).
Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.
If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.
Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.
Supporting data
The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.
Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.
Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.
About priority review, accelerated assessment
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).
Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.
If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.
Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.
Supporting data
The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.
Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.
Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.
About priority review, accelerated assessment
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).
Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.
If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.
Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.
Supporting data
The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.
Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.
Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.
About priority review, accelerated assessment
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
HLF proves ‘critical’ for HSC quiescence
Preclinical research suggests hepatic leukemia factor (HLF) protects hematopoietic stem cells (HSCs) by helping them maintain quiescence.
Researchers found that HLF-deficient HSCs were more sensitive than wild-type HSCs to chemotherapy and irradiation.
After transplantation in mice, HLF-deficient HSCs were less able than wild-type HSCs to reconstitute hematopoiesis.
These findings were published in Cell Reports.
“The study confirms several previous studies that show the HLF gene’s significance in blood formation,” said study author Mattias Magnusson, PhD, of Lund University in Sweden.
“Identifying the factors that control blood stem cells provides knowledge needed to be able to propagate the stem cells outside the body. This has long been one of the major goals in the blood stem cell field, as it would increase possibilities for blood stem cell transplantation when, for example, there is a shortage of stem cells or donors. In addition, we will increase our understanding of how leukemia arises.”
Previous research by Dr Magnusson and his colleagues suggested that HLF may regulate HSCs in both normal and malignant hematopoiesis.
With the current study, the researchers found that HLF was “dispensable for steady-state hematopoiesis.” In fact, HLF-knockout mice had “essentially normal hematopoietic parameters” in steady-state conditions.
However, when HLF-deficient HSCs were serially transplanted in mice, the cells showed a reduction in regenerative potential, when compared to wild-type HSCs.
Additionally, mice with HLF-deficient HSCs exhibited increased sensitivity to the myeloablative agent 5-fluorouracil and reduced survival after sublethal irradiation, as compared to control mice.
“It’s surprising that the mice [initially] lived a normal life without the HLF gene, but when they had an acute need for new blood after an external damage such as cytostatic treatment, the mice did not survive,” Dr Magnusson said.
“All the blood stem cells were eliminated by the treatment, as they were active rather than in a resting state. Without the HLF gene, the blood stem cells were no longer protected against cytostatic treatment or other types of stress such as transplantation.”
Taking their findings together, Dr Magnusson and his colleagues concluded that HLF is a “critical” regulator of HSC quiescence and “essential” for maintaining HSCs’ ability to produce new blood.
Preclinical research suggests hepatic leukemia factor (HLF) protects hematopoietic stem cells (HSCs) by helping them maintain quiescence.
Researchers found that HLF-deficient HSCs were more sensitive than wild-type HSCs to chemotherapy and irradiation.
After transplantation in mice, HLF-deficient HSCs were less able than wild-type HSCs to reconstitute hematopoiesis.
These findings were published in Cell Reports.
“The study confirms several previous studies that show the HLF gene’s significance in blood formation,” said study author Mattias Magnusson, PhD, of Lund University in Sweden.
“Identifying the factors that control blood stem cells provides knowledge needed to be able to propagate the stem cells outside the body. This has long been one of the major goals in the blood stem cell field, as it would increase possibilities for blood stem cell transplantation when, for example, there is a shortage of stem cells or donors. In addition, we will increase our understanding of how leukemia arises.”
Previous research by Dr Magnusson and his colleagues suggested that HLF may regulate HSCs in both normal and malignant hematopoiesis.
With the current study, the researchers found that HLF was “dispensable for steady-state hematopoiesis.” In fact, HLF-knockout mice had “essentially normal hematopoietic parameters” in steady-state conditions.
However, when HLF-deficient HSCs were serially transplanted in mice, the cells showed a reduction in regenerative potential, when compared to wild-type HSCs.
Additionally, mice with HLF-deficient HSCs exhibited increased sensitivity to the myeloablative agent 5-fluorouracil and reduced survival after sublethal irradiation, as compared to control mice.
“It’s surprising that the mice [initially] lived a normal life without the HLF gene, but when they had an acute need for new blood after an external damage such as cytostatic treatment, the mice did not survive,” Dr Magnusson said.
“All the blood stem cells were eliminated by the treatment, as they were active rather than in a resting state. Without the HLF gene, the blood stem cells were no longer protected against cytostatic treatment or other types of stress such as transplantation.”
Taking their findings together, Dr Magnusson and his colleagues concluded that HLF is a “critical” regulator of HSC quiescence and “essential” for maintaining HSCs’ ability to produce new blood.
Preclinical research suggests hepatic leukemia factor (HLF) protects hematopoietic stem cells (HSCs) by helping them maintain quiescence.
Researchers found that HLF-deficient HSCs were more sensitive than wild-type HSCs to chemotherapy and irradiation.
After transplantation in mice, HLF-deficient HSCs were less able than wild-type HSCs to reconstitute hematopoiesis.
These findings were published in Cell Reports.
“The study confirms several previous studies that show the HLF gene’s significance in blood formation,” said study author Mattias Magnusson, PhD, of Lund University in Sweden.
“Identifying the factors that control blood stem cells provides knowledge needed to be able to propagate the stem cells outside the body. This has long been one of the major goals in the blood stem cell field, as it would increase possibilities for blood stem cell transplantation when, for example, there is a shortage of stem cells or donors. In addition, we will increase our understanding of how leukemia arises.”
Previous research by Dr Magnusson and his colleagues suggested that HLF may regulate HSCs in both normal and malignant hematopoiesis.
With the current study, the researchers found that HLF was “dispensable for steady-state hematopoiesis.” In fact, HLF-knockout mice had “essentially normal hematopoietic parameters” in steady-state conditions.
However, when HLF-deficient HSCs were serially transplanted in mice, the cells showed a reduction in regenerative potential, when compared to wild-type HSCs.
Additionally, mice with HLF-deficient HSCs exhibited increased sensitivity to the myeloablative agent 5-fluorouracil and reduced survival after sublethal irradiation, as compared to control mice.
“It’s surprising that the mice [initially] lived a normal life without the HLF gene, but when they had an acute need for new blood after an external damage such as cytostatic treatment, the mice did not survive,” Dr Magnusson said.
“All the blood stem cells were eliminated by the treatment, as they were active rather than in a resting state. Without the HLF gene, the blood stem cells were no longer protected against cytostatic treatment or other types of stress such as transplantation.”
Taking their findings together, Dr Magnusson and his colleagues concluded that HLF is a “critical” regulator of HSC quiescence and “essential” for maintaining HSCs’ ability to produce new blood.
Pearls in Dermatology: 2017
The Pearls in Dermatology collection consists of our popular pearls from the year in one convenient file. Topics include:
- Nail psoriasis and psoriasis on the hands and feet
- Genital wart treatment
- Isotretinoin for acne
- Cosmeceuticals for rosacea
- Surgical technique with the flexible scalpel blade
Editor’s Commentary provided by Vincent A. DeLeo, MD, Editor-in-Chief, Cutis.
Save this collection, print it, and/or share it with your colleagues. We hope this comprehensive collection will positively impact how you manage patients.
The Pearls in Dermatology collection consists of our popular pearls from the year in one convenient file. Topics include:
- Nail psoriasis and psoriasis on the hands and feet
- Genital wart treatment
- Isotretinoin for acne
- Cosmeceuticals for rosacea
- Surgical technique with the flexible scalpel blade
Editor’s Commentary provided by Vincent A. DeLeo, MD, Editor-in-Chief, Cutis.
Save this collection, print it, and/or share it with your colleagues. We hope this comprehensive collection will positively impact how you manage patients.
The Pearls in Dermatology collection consists of our popular pearls from the year in one convenient file. Topics include:
- Nail psoriasis and psoriasis on the hands and feet
- Genital wart treatment
- Isotretinoin for acne
- Cosmeceuticals for rosacea
- Surgical technique with the flexible scalpel blade
Editor’s Commentary provided by Vincent A. DeLeo, MD, Editor-in-Chief, Cutis.
Save this collection, print it, and/or share it with your colleagues. We hope this comprehensive collection will positively impact how you manage patients.
Atopic march largely attributed to genetic factors
according to a systematic review.
PhD candidate Sabria Khan and her colleagues at the Centre for Epidemiology and Biostatistics at the University of Melbourne said that the atopic march concept “asserts that allergic diseases start in early life with eczema, progress through food allergy, and culminate with hay fever and asthma.”
This systematic review of ten twin and sibling studies looked at known, measured environmental and genetic influences on the associations between the atopic phenotypes of the atopic march.
The studies of asthma and hay fever suggested that the prevalence of having both conditions was high (32%) and that they were more likely to occur together in monozygotic twins than they were in dizygotic twins. Similarly, other studies found a high phenotypic overlap between eczema and asthma and between eczema and hay fever, which was more pronounced in monozygotic twins than in dizygotic twins.
“Asthma is linked to hay fever and eczema through intermediate phenotypes like clinical measures of lung function, physiological measures of airway responsiveness and the biomarker exhaled nitric oxide, all of which are influenced by hereditary factors,” the authors said.
Overall, they concluded that genetic factors account for 75% of eczema cases, 70%-91% of asthma cases, and 72%-84% of hay fever cases, making them all highly heritable diseases.
“Our study found that the contribution of shared environmental factors to the proportion of correlation are very low (from 4% to 18%) and does not explain the familial patterns seen for asthma and hay fever,” they reported. “This finding contradicts various analyses where smoking behavior, indoor-outdoor pollution, and house dust mites were found to be significant risk factor for asthma and hay fever that are shared by siblings.”
The authors commented that preventing the onset of the atopic march, or arresting its development, could have significant public health implications. They suggested that interventions such as oral antihistamines could be introduced either before a child gets eczema or before a child with eczema goes on to develop asthma or hay fever. “Two randomized controlled trials showed moisturizing the skin can prevent mild to moderate eczema, and long-term studies are needed to see whether such intervention will prevent development of asthma and hay fever,” they said.
No conflicts of interest were declared.
SOURCE: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.
according to a systematic review.
PhD candidate Sabria Khan and her colleagues at the Centre for Epidemiology and Biostatistics at the University of Melbourne said that the atopic march concept “asserts that allergic diseases start in early life with eczema, progress through food allergy, and culminate with hay fever and asthma.”
This systematic review of ten twin and sibling studies looked at known, measured environmental and genetic influences on the associations between the atopic phenotypes of the atopic march.
The studies of asthma and hay fever suggested that the prevalence of having both conditions was high (32%) and that they were more likely to occur together in monozygotic twins than they were in dizygotic twins. Similarly, other studies found a high phenotypic overlap between eczema and asthma and between eczema and hay fever, which was more pronounced in monozygotic twins than in dizygotic twins.
“Asthma is linked to hay fever and eczema through intermediate phenotypes like clinical measures of lung function, physiological measures of airway responsiveness and the biomarker exhaled nitric oxide, all of which are influenced by hereditary factors,” the authors said.
Overall, they concluded that genetic factors account for 75% of eczema cases, 70%-91% of asthma cases, and 72%-84% of hay fever cases, making them all highly heritable diseases.
“Our study found that the contribution of shared environmental factors to the proportion of correlation are very low (from 4% to 18%) and does not explain the familial patterns seen for asthma and hay fever,” they reported. “This finding contradicts various analyses where smoking behavior, indoor-outdoor pollution, and house dust mites were found to be significant risk factor for asthma and hay fever that are shared by siblings.”
The authors commented that preventing the onset of the atopic march, or arresting its development, could have significant public health implications. They suggested that interventions such as oral antihistamines could be introduced either before a child gets eczema or before a child with eczema goes on to develop asthma or hay fever. “Two randomized controlled trials showed moisturizing the skin can prevent mild to moderate eczema, and long-term studies are needed to see whether such intervention will prevent development of asthma and hay fever,” they said.
No conflicts of interest were declared.
SOURCE: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.
according to a systematic review.
PhD candidate Sabria Khan and her colleagues at the Centre for Epidemiology and Biostatistics at the University of Melbourne said that the atopic march concept “asserts that allergic diseases start in early life with eczema, progress through food allergy, and culminate with hay fever and asthma.”
This systematic review of ten twin and sibling studies looked at known, measured environmental and genetic influences on the associations between the atopic phenotypes of the atopic march.
The studies of asthma and hay fever suggested that the prevalence of having both conditions was high (32%) and that they were more likely to occur together in monozygotic twins than they were in dizygotic twins. Similarly, other studies found a high phenotypic overlap between eczema and asthma and between eczema and hay fever, which was more pronounced in monozygotic twins than in dizygotic twins.
“Asthma is linked to hay fever and eczema through intermediate phenotypes like clinical measures of lung function, physiological measures of airway responsiveness and the biomarker exhaled nitric oxide, all of which are influenced by hereditary factors,” the authors said.
Overall, they concluded that genetic factors account for 75% of eczema cases, 70%-91% of asthma cases, and 72%-84% of hay fever cases, making them all highly heritable diseases.
“Our study found that the contribution of shared environmental factors to the proportion of correlation are very low (from 4% to 18%) and does not explain the familial patterns seen for asthma and hay fever,” they reported. “This finding contradicts various analyses where smoking behavior, indoor-outdoor pollution, and house dust mites were found to be significant risk factor for asthma and hay fever that are shared by siblings.”
The authors commented that preventing the onset of the atopic march, or arresting its development, could have significant public health implications. They suggested that interventions such as oral antihistamines could be introduced either before a child gets eczema or before a child with eczema goes on to develop asthma or hay fever. “Two randomized controlled trials showed moisturizing the skin can prevent mild to moderate eczema, and long-term studies are needed to see whether such intervention will prevent development of asthma and hay fever,” they said.
No conflicts of interest were declared.
SOURCE: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.
FROM ALLERGY
Key clinical point: Twin and sibling studies suggest that genetics play a far more significant role than environmental factors in the progression of atopic disease in childhood known as the “atopic march.”
Major finding: Genetic factors account for 75% of eczema, 70%-91% of asthma, and 72%-84% of hay fever.
Data source: Systematic review of ten twin and sibling studies.
Disclosures: No conflicts of interest were declared.
Source: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.