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.

Bruce Jancin/Frontline Medical News

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.

bjancin@frontlinemedcom.com

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.

Bruce Jancin/Frontline Medical News

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.

bjancin@frontlinemedcom.com

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.

Bruce Jancin/Frontline Medical News

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.

bjancin@frontlinemedcom.com

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.”

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.

Malignant plasma cells

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.

Malignant plasma cells

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.

Malignant plasma cells

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.

Photo from Novartis

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.

Photo from Novartis

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.

Photo from Novartis

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.

HSCs in the bone marrow

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.

HSCs in the bone marrow

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.

HSCs in the bone marrow

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.

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.

Genetics appear to play a far more significant role than environment in the “atopic march” of sequential allergy and respiratory disorders in children, 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.”

aniaostudio/Thinkstock

SOURCE: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.

Genetics appear to play a far more significant role than environment in the “atopic march” of sequential allergy and respiratory disorders in children, 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.”

aniaostudio/Thinkstock

SOURCE: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.

Genetics appear to play a far more significant role than environment in the “atopic march” of sequential allergy and respiratory disorders in children, 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.”

aniaostudio/Thinkstock

SOURCE: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.

Non–vitamin K antagonist anticoagulants (NOACs, also called novel or direct oral anticoagulants) are commonly used to treat and prevent venous thromboembolism (VTE) and to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. These agents, which include the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa), and the competitive thrombin inhibitor dabigatran (Pradaxa), often are preferred over warfarin because of their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. However, the acute care of patients taking NOACS can be challenging, because only dabigatran has an approved reversal agent, and none have readily available, reliable measurement assays. The American Heart Association (AHA) published a statement on the periprocedural and acute care management of patients taking NOACs. Here are the findings and recommendations of the AHA that are most relevant to primary care physicians.

Measurement

While all NOACs affect coagulation tests, their effect on prothrombin time and activated partial thromboplastin time is neither predictable nor an accurate reflection of the degree of anticoagulation. Instead, use the time of last drug ingestion and the patient’s creatinine clearance to estimate the anticoagulation effect. Dabigatran takes 1 hour to reach peak effect, or 2 hours if taken with food. Its half-life is 12-17 hours, on the higher end in the elderly and in those with moderate renal impairment. In those with severe renal impairment, half-life can be 28 hours. Rivaroxaban’s time to peak is 2-4 hours, and its half-life is 5-9 hours or up to 13 in the elderly. Apixaban’s time to peak is 3-4 hours and its half-life is about 12 hours. An antifactor Xa activity assay does provide a quantitative assessment of the factor Xa inhibitors.

Kidney injury

Acute kidney injury increases risk of bleeding while taking a NOAC. Monitor these patients closely and consider temporarily switching to a different anticoagulant in the setting of kidney injury.

Bleeding

Lack of reversibility is a common concern. Use 5 g of IV idarucizumab (Praxbind) to reverse dabigatran within minutes in a patient experiencing major bleeding. Hemodialysis, which removes about half of dabigatran in 4 hours, is a suitable option in acute kidney injury or in patients with a creatinine clearance under 30mL/min.

Options are more limited for the Xa inhibitors, because there are no available reversal agents and hemodialysis does not clear these highly protein-bound drugs. While data are limited, prothrombin complex concentrate may be given for patients on rivaroxaban, apixaban, or edoxaban who are experiencing an intracranial hemorrhage or other form of severe bleeding. Simply holding the NOAC is acceptable for minor bleeding.
 

Overdose

Activated charcoal to induce vomiting will work within 1-2 hours of drug ingestion.

Intracranial hemorrhage

Assume that a patient taking a NOAC who displays any acute neurologic change is experiencing an intracranial hemorrhage until proven otherwise. After CT confirmation, reverse dabigatran with idarucizumab, or give prothrombin complex concentrate to patients on other NOACs.

Ischemic stroke

Patients who suffer an ischemic stroke despite NOAC therapy are not candidates for tissue plasminogen activators.

The primary care physician is likely to be involved in the decision of whether, when, and for how long to resume anticoagulation therapy after a stroke. The statement says, “guidelines support withholding oral anticoagulation until 1-2 weeks after stroke among individuals with NVAF [nonvalvular atrial fibrillation], with shorter times for those with transient ischemic attack or small, nondisabling strokes and longer times for moderate to severe strokes.” In addition, it is worthwhile to consider medication nonadherence if no other etiology for the stroke is found; patients who miss doses may benefit more from warfarin because of its longer half-life.
 

Procedures and surgeries

Each year approximately 10% of patients on anticoagulation require surgery or other invasive procedures, and 20% require a minor procedure. To determine whether to interrupt NOAC therapy prior to a procedure, first determine the procedure’s bleeding risk. Patients undergoing procedures with low risk of bleeding, including minor dental, dermatologic, and ophthalmologic procedures, and endoscopies without biopsies, do not require interruption. For procedures with a moderate bleeding risk (including cardiac ablation, endoscopy with biopsies, radial artery catheterization) or high bleeding risk (including major surgery and cardiac catheterization via femoral artery), the patient’s thromboembolic risk should be evaluated using the medical history and the CHA2DS2 VASc score. NOACs should be stopped for 24-48 hours prior to the moderate to high-risk procedures. Dabigatran should be held for 72 hours for patients with creatinine clearance less than 50mL/min. Bridging therapy with heparin is not recommended for patients taking NOACS who are to have surgery. The decision about when to restart NOAC is based on the risk of thromboembolism and the bleeding risk of surgery.

Spinal or epidural anesthesia

Anesthesia guidelines recommend holding NOACs 3-5 days prior to the intervention, however, this increases risk of TE and studies have shown a very low incidence of hematoma in patients anticoagulated with a NOAC. For patients with a high risk of VTE, the NOAC can be resumed 12 hours post-procedure.

The bottom line

NOACS are commonly used for treatment and prophylaxis of VTE and atrial fibrillation and are often preferred over warfarin due to their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. The AHA scientific statement gives guidance on managing NOACS in the face of acute bleeding as well as during and after procedures. NOACS should be stopped 24-48 hours prior to major surgeries and may be restarted based on weighing the risk of bleeding and risk of thromboembolism.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Oh is a third-year resident in the family medicine residency program at Abington Jefferson Health.

Reference

Raval AN et al. Management of patients on non–vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the American Heart Association. Circulation. 2017 Feb 6;135[10]:e604-e33. doi: 10.1161/CIR.0000000000000477

Non–vitamin K antagonist anticoagulants (NOACs, also called novel or direct oral anticoagulants) are commonly used to treat and prevent venous thromboembolism (VTE) and to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. These agents, which include the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa), and the competitive thrombin inhibitor dabigatran (Pradaxa), often are preferred over warfarin because of their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. However, the acute care of patients taking NOACS can be challenging, because only dabigatran has an approved reversal agent, and none have readily available, reliable measurement assays. The American Heart Association (AHA) published a statement on the periprocedural and acute care management of patients taking NOACs. Here are the findings and recommendations of the AHA that are most relevant to primary care physicians.

Measurement

While all NOACs affect coagulation tests, their effect on prothrombin time and activated partial thromboplastin time is neither predictable nor an accurate reflection of the degree of anticoagulation. Instead, use the time of last drug ingestion and the patient’s creatinine clearance to estimate the anticoagulation effect. Dabigatran takes 1 hour to reach peak effect, or 2 hours if taken with food. Its half-life is 12-17 hours, on the higher end in the elderly and in those with moderate renal impairment. In those with severe renal impairment, half-life can be 28 hours. Rivaroxaban’s time to peak is 2-4 hours, and its half-life is 5-9 hours or up to 13 in the elderly. Apixaban’s time to peak is 3-4 hours and its half-life is about 12 hours. An antifactor Xa activity assay does provide a quantitative assessment of the factor Xa inhibitors.

Kidney injury

Acute kidney injury increases risk of bleeding while taking a NOAC. Monitor these patients closely and consider temporarily switching to a different anticoagulant in the setting of kidney injury.

Bleeding

Lack of reversibility is a common concern. Use 5 g of IV idarucizumab (Praxbind) to reverse dabigatran within minutes in a patient experiencing major bleeding. Hemodialysis, which removes about half of dabigatran in 4 hours, is a suitable option in acute kidney injury or in patients with a creatinine clearance under 30mL/min.

Options are more limited for the Xa inhibitors, because there are no available reversal agents and hemodialysis does not clear these highly protein-bound drugs. While data are limited, prothrombin complex concentrate may be given for patients on rivaroxaban, apixaban, or edoxaban who are experiencing an intracranial hemorrhage or other form of severe bleeding. Simply holding the NOAC is acceptable for minor bleeding.
 

Overdose

Activated charcoal to induce vomiting will work within 1-2 hours of drug ingestion.

Intracranial hemorrhage

Assume that a patient taking a NOAC who displays any acute neurologic change is experiencing an intracranial hemorrhage until proven otherwise. After CT confirmation, reverse dabigatran with idarucizumab, or give prothrombin complex concentrate to patients on other NOACs.

Ischemic stroke

Patients who suffer an ischemic stroke despite NOAC therapy are not candidates for tissue plasminogen activators.

The primary care physician is likely to be involved in the decision of whether, when, and for how long to resume anticoagulation therapy after a stroke. The statement says, “guidelines support withholding oral anticoagulation until 1-2 weeks after stroke among individuals with NVAF [nonvalvular atrial fibrillation], with shorter times for those with transient ischemic attack or small, nondisabling strokes and longer times for moderate to severe strokes.” In addition, it is worthwhile to consider medication nonadherence if no other etiology for the stroke is found; patients who miss doses may benefit more from warfarin because of its longer half-life.
 

Procedures and surgeries

Each year approximately 10% of patients on anticoagulation require surgery or other invasive procedures, and 20% require a minor procedure. To determine whether to interrupt NOAC therapy prior to a procedure, first determine the procedure’s bleeding risk. Patients undergoing procedures with low risk of bleeding, including minor dental, dermatologic, and ophthalmologic procedures, and endoscopies without biopsies, do not require interruption. For procedures with a moderate bleeding risk (including cardiac ablation, endoscopy with biopsies, radial artery catheterization) or high bleeding risk (including major surgery and cardiac catheterization via femoral artery), the patient’s thromboembolic risk should be evaluated using the medical history and the CHA2DS2 VASc score. NOACs should be stopped for 24-48 hours prior to the moderate to high-risk procedures. Dabigatran should be held for 72 hours for patients with creatinine clearance less than 50mL/min. Bridging therapy with heparin is not recommended for patients taking NOACS who are to have surgery. The decision about when to restart NOAC is based on the risk of thromboembolism and the bleeding risk of surgery.

Spinal or epidural anesthesia

Anesthesia guidelines recommend holding NOACs 3-5 days prior to the intervention, however, this increases risk of TE and studies have shown a very low incidence of hematoma in patients anticoagulated with a NOAC. For patients with a high risk of VTE, the NOAC can be resumed 12 hours post-procedure.

The bottom line

NOACS are commonly used for treatment and prophylaxis of VTE and atrial fibrillation and are often preferred over warfarin due to their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. The AHA scientific statement gives guidance on managing NOACS in the face of acute bleeding as well as during and after procedures. NOACS should be stopped 24-48 hours prior to major surgeries and may be restarted based on weighing the risk of bleeding and risk of thromboembolism.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Oh is a third-year resident in the family medicine residency program at Abington Jefferson Health.

Reference

Raval AN et al. Management of patients on non–vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the American Heart Association. Circulation. 2017 Feb 6;135[10]:e604-e33. doi: 10.1161/CIR.0000000000000477

Non–vitamin K antagonist anticoagulants (NOACs, also called novel or direct oral anticoagulants) are commonly used to treat and prevent venous thromboembolism (VTE) and to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. These agents, which include the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa), and the competitive thrombin inhibitor dabigatran (Pradaxa), often are preferred over warfarin because of their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. However, the acute care of patients taking NOACS can be challenging, because only dabigatran has an approved reversal agent, and none have readily available, reliable measurement assays. The American Heart Association (AHA) published a statement on the periprocedural and acute care management of patients taking NOACs. Here are the findings and recommendations of the AHA that are most relevant to primary care physicians.

Measurement

While all NOACs affect coagulation tests, their effect on prothrombin time and activated partial thromboplastin time is neither predictable nor an accurate reflection of the degree of anticoagulation. Instead, use the time of last drug ingestion and the patient’s creatinine clearance to estimate the anticoagulation effect. Dabigatran takes 1 hour to reach peak effect, or 2 hours if taken with food. Its half-life is 12-17 hours, on the higher end in the elderly and in those with moderate renal impairment. In those with severe renal impairment, half-life can be 28 hours. Rivaroxaban’s time to peak is 2-4 hours, and its half-life is 5-9 hours or up to 13 in the elderly. Apixaban’s time to peak is 3-4 hours and its half-life is about 12 hours. An antifactor Xa activity assay does provide a quantitative assessment of the factor Xa inhibitors.

Kidney injury

Acute kidney injury increases risk of bleeding while taking a NOAC. Monitor these patients closely and consider temporarily switching to a different anticoagulant in the setting of kidney injury.

Bleeding

Lack of reversibility is a common concern. Use 5 g of IV idarucizumab (Praxbind) to reverse dabigatran within minutes in a patient experiencing major bleeding. Hemodialysis, which removes about half of dabigatran in 4 hours, is a suitable option in acute kidney injury or in patients with a creatinine clearance under 30mL/min.

Options are more limited for the Xa inhibitors, because there are no available reversal agents and hemodialysis does not clear these highly protein-bound drugs. While data are limited, prothrombin complex concentrate may be given for patients on rivaroxaban, apixaban, or edoxaban who are experiencing an intracranial hemorrhage or other form of severe bleeding. Simply holding the NOAC is acceptable for minor bleeding.
 

Overdose

Activated charcoal to induce vomiting will work within 1-2 hours of drug ingestion.

Intracranial hemorrhage

Assume that a patient taking a NOAC who displays any acute neurologic change is experiencing an intracranial hemorrhage until proven otherwise. After CT confirmation, reverse dabigatran with idarucizumab, or give prothrombin complex concentrate to patients on other NOACs.

Ischemic stroke

Patients who suffer an ischemic stroke despite NOAC therapy are not candidates for tissue plasminogen activators.

The primary care physician is likely to be involved in the decision of whether, when, and for how long to resume anticoagulation therapy after a stroke. The statement says, “guidelines support withholding oral anticoagulation until 1-2 weeks after stroke among individuals with NVAF [nonvalvular atrial fibrillation], with shorter times for those with transient ischemic attack or small, nondisabling strokes and longer times for moderate to severe strokes.” In addition, it is worthwhile to consider medication nonadherence if no other etiology for the stroke is found; patients who miss doses may benefit more from warfarin because of its longer half-life.
 

Procedures and surgeries

Each year approximately 10% of patients on anticoagulation require surgery or other invasive procedures, and 20% require a minor procedure. To determine whether to interrupt NOAC therapy prior to a procedure, first determine the procedure’s bleeding risk. Patients undergoing procedures with low risk of bleeding, including minor dental, dermatologic, and ophthalmologic procedures, and endoscopies without biopsies, do not require interruption. For procedures with a moderate bleeding risk (including cardiac ablation, endoscopy with biopsies, radial artery catheterization) or high bleeding risk (including major surgery and cardiac catheterization via femoral artery), the patient’s thromboembolic risk should be evaluated using the medical history and the CHA2DS2 VASc score. NOACs should be stopped for 24-48 hours prior to the moderate to high-risk procedures. Dabigatran should be held for 72 hours for patients with creatinine clearance less than 50mL/min. Bridging therapy with heparin is not recommended for patients taking NOACS who are to have surgery. The decision about when to restart NOAC is based on the risk of thromboembolism and the bleeding risk of surgery.

Spinal or epidural anesthesia

Anesthesia guidelines recommend holding NOACs 3-5 days prior to the intervention, however, this increases risk of TE and studies have shown a very low incidence of hematoma in patients anticoagulated with a NOAC. For patients with a high risk of VTE, the NOAC can be resumed 12 hours post-procedure.

The bottom line

NOACS are commonly used for treatment and prophylaxis of VTE and atrial fibrillation and are often preferred over warfarin due to their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. The AHA scientific statement gives guidance on managing NOACS in the face of acute bleeding as well as during and after procedures. NOACS should be stopped 24-48 hours prior to major surgeries and may be restarted based on weighing the risk of bleeding and risk of thromboembolism.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Oh is a third-year resident in the family medicine residency program at Abington Jefferson Health.

Reference

Raval AN et al. Management of patients on non–vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the American Heart Association. Circulation. 2017 Feb 6;135[10]:e604-e33. doi: 10.1161/CIR.0000000000000477

Patients with newly diagnosed advanced-stage ovarian cancer who were referred to receive three cycles of neoadjuvant chemotherapy experienced statistically significant improved recurrence-free survival and overall survival from hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery, results of a phase 3 trial showed.

After 4.7 years’ median follow-up, 89% of patients who received surgery with no HIPEC had disease recurrence or death, compared with 81% of patients treated with HIPEC (hazard ratio, 0.66; P = .003). Patients in the HIPEC cohort experienced recurrence-free survival a median of 3.5 months longer than patients who received surgery alone (10.7 months vs. 14.2 months), Willemien J. van Driel, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and her colleagues reported in the New England Journal of Medicine.

Dr. van Driel and her coauthors also reported a median 11.8 months increased overall survival (33.9 months vs. 45.7 months) for HIPEC, compared with surgery alone.

Both recurrence-free survival and overall survival remained consistently beneficial for patients in the HIPEC group across prespecified stratification factors and subgroups, including age, histology type, regional involvement, and previous surgery, according to the researchers.

They also reported that no significant differences between the two groups were noted in the incidence of adverse events of any grade. In total, grade 3 or 4 adverse events were reported by 32 patients (27%) who received HIPEC and 30 patients (25%) who received surgery (P = .76); the most common were abdominal pain, infection, and ileus.

Combination treatment with intravenous and intraperitoneal chemotherapy has been shown to prolong overall survival after primary cytoreductive surgery, according to the authors.

“Catheter-related problems, increased demands on the patient, and gastrointestinal and renal side effects have hampered the adoption of this approach in most countries,” the researchers wrote. “Hyperthermia increases the penetration of chemotherapy at the peritoneal surface and increases the sensitivity of the cancer to chemotherapy by impairing DNA repair [and] … can circumvent most of these drawbacks while maintaining its advantages.”

This research was supported by the Dutch Cancer Society. Dr. van Driel reported no relevant financial disclosures. Two other researchers reported funding from various pharmaceutical companies as well as the KFW–Dutch Cancer Foundation.

op@frontlinemedcom.com

SOURCE: van Driel WJ et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMoa1708618.
 

Patients with newly diagnosed advanced-stage ovarian cancer who were referred to receive three cycles of neoadjuvant chemotherapy experienced statistically significant improved recurrence-free survival and overall survival from hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery, results of a phase 3 trial showed.

After 4.7 years’ median follow-up, 89% of patients who received surgery with no HIPEC had disease recurrence or death, compared with 81% of patients treated with HIPEC (hazard ratio, 0.66; P = .003). Patients in the HIPEC cohort experienced recurrence-free survival a median of 3.5 months longer than patients who received surgery alone (10.7 months vs. 14.2 months), Willemien J. van Driel, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and her colleagues reported in the New England Journal of Medicine.

Dr. van Driel and her coauthors also reported a median 11.8 months increased overall survival (33.9 months vs. 45.7 months) for HIPEC, compared with surgery alone.

Both recurrence-free survival and overall survival remained consistently beneficial for patients in the HIPEC group across prespecified stratification factors and subgroups, including age, histology type, regional involvement, and previous surgery, according to the researchers.

They also reported that no significant differences between the two groups were noted in the incidence of adverse events of any grade. In total, grade 3 or 4 adverse events were reported by 32 patients (27%) who received HIPEC and 30 patients (25%) who received surgery (P = .76); the most common were abdominal pain, infection, and ileus.

Combination treatment with intravenous and intraperitoneal chemotherapy has been shown to prolong overall survival after primary cytoreductive surgery, according to the authors.

“Catheter-related problems, increased demands on the patient, and gastrointestinal and renal side effects have hampered the adoption of this approach in most countries,” the researchers wrote. “Hyperthermia increases the penetration of chemotherapy at the peritoneal surface and increases the sensitivity of the cancer to chemotherapy by impairing DNA repair [and] … can circumvent most of these drawbacks while maintaining its advantages.”

This research was supported by the Dutch Cancer Society. Dr. van Driel reported no relevant financial disclosures. Two other researchers reported funding from various pharmaceutical companies as well as the KFW–Dutch Cancer Foundation.

op@frontlinemedcom.com

SOURCE: van Driel WJ et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMoa1708618.
 

Patients with newly diagnosed advanced-stage ovarian cancer who were referred to receive three cycles of neoadjuvant chemotherapy experienced statistically significant improved recurrence-free survival and overall survival from hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery, results of a phase 3 trial showed.

After 4.7 years’ median follow-up, 89% of patients who received surgery with no HIPEC had disease recurrence or death, compared with 81% of patients treated with HIPEC (hazard ratio, 0.66; P = .003). Patients in the HIPEC cohort experienced recurrence-free survival a median of 3.5 months longer than patients who received surgery alone (10.7 months vs. 14.2 months), Willemien J. van Driel, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and her colleagues reported in the New England Journal of Medicine.

Dr. van Driel and her coauthors also reported a median 11.8 months increased overall survival (33.9 months vs. 45.7 months) for HIPEC, compared with surgery alone.

Both recurrence-free survival and overall survival remained consistently beneficial for patients in the HIPEC group across prespecified stratification factors and subgroups, including age, histology type, regional involvement, and previous surgery, according to the researchers.

They also reported that no significant differences between the two groups were noted in the incidence of adverse events of any grade. In total, grade 3 or 4 adverse events were reported by 32 patients (27%) who received HIPEC and 30 patients (25%) who received surgery (P = .76); the most common were abdominal pain, infection, and ileus.

Combination treatment with intravenous and intraperitoneal chemotherapy has been shown to prolong overall survival after primary cytoreductive surgery, according to the authors.

“Catheter-related problems, increased demands on the patient, and gastrointestinal and renal side effects have hampered the adoption of this approach in most countries,” the researchers wrote. “Hyperthermia increases the penetration of chemotherapy at the peritoneal surface and increases the sensitivity of the cancer to chemotherapy by impairing DNA repair [and] … can circumvent most of these drawbacks while maintaining its advantages.”

This research was supported by the Dutch Cancer Society. Dr. van Driel reported no relevant financial disclosures. Two other researchers reported funding from various pharmaceutical companies as well as the KFW–Dutch Cancer Foundation.

op@frontlinemedcom.com

SOURCE: van Driel WJ et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMoa1708618.