Looking for a research opportunity? Check our updated website for current programs in your area. If your institution has an opportunity to promote, let us know at [email protected].

Looking for a research opportunity? Check our updated website for current programs in your area. If your institution has an opportunity to promote, let us know at [email protected].

Looking for a research opportunity? Check our updated website for current programs in your area. If your institution has an opportunity to promote, let us know at [email protected].

Help build the Vascular Annual Meeting educational program for the new “Ask the Experts” sessions, to be held daily, Wednesday through Saturday. Topics are coding, aortic care for occlusive disease, hemodialysis and PAD. Learn more about case submission here.

And if you haven’t registered for VAM yet, do so! The premier meeting for vascular surgeons is just five weeks (and one day) away. Learn more and register here. And obtain a hotel room here.

Help build the Vascular Annual Meeting educational program for the new “Ask the Experts” sessions, to be held daily, Wednesday through Saturday. Topics are coding, aortic care for occlusive disease, hemodialysis and PAD. Learn more about case submission here.

And if you haven’t registered for VAM yet, do so! The premier meeting for vascular surgeons is just five weeks (and one day) away. Learn more and register here. And obtain a hotel room here.

Help build the Vascular Annual Meeting educational program for the new “Ask the Experts” sessions, to be held daily, Wednesday through Saturday. Topics are coding, aortic care for occlusive disease, hemodialysis and PAD. Learn more about case submission here.

And if you haven’t registered for VAM yet, do so! The premier meeting for vascular surgeons is just five weeks (and one day) away. Learn more and register here. And obtain a hotel room here.

Did you miss the April 30 webinar on "Negotiating Physician Employment Contracts," presented by the SVS and the SVS Community Practice Committee? Materials -- available only to SVS members -- can be viewed here. Topics include benefits, call pay, termination rights, non-compete clauses, tenure opportunities and more.

Did you miss the April 30 webinar on "Negotiating Physician Employment Contracts," presented by the SVS and the SVS Community Practice Committee? Materials -- available only to SVS members -- can be viewed here. Topics include benefits, call pay, termination rights, non-compete clauses, tenure opportunities and more.

Did you miss the April 30 webinar on "Negotiating Physician Employment Contracts," presented by the SVS and the SVS Community Practice Committee? Materials -- available only to SVS members -- can be viewed here. Topics include benefits, call pay, termination rights, non-compete clauses, tenure opportunities and more.

BOSTON – Device-related thrombus (DRT) does not occur often after left atrial appendage closure with the Watchman device. When it does, however, it is associated with a significantly higher rate of stroke and systemic embolism compared with that of patients with no DRT, according to a recent analysis presented at the annual scientific sessions of the Heart Rhythm Society.

Courtesy Boston Scientific

Given the negative implications of DRT, a judicious surveillance strategy should be considered, especially when DRT risk factors are present, investigators said in a report on the study, which was published simultaneously in Circulation.

“Certainly, DRT is associated with an increased risk of stroke, and therapeutic anticoagulation should be resumed when discovered with rigorous transesophageal echocardiography follow-up to ensure resolution,” noted senior investigator Vivek Y. Reddy, MD.

Despite the higher rates of all strokes, ischemic strokes, and hemorrhagic strokes linked with DRT, the complication did not link with a higher rate of all-cause mortality compared with patients who never had a DRT. The results also suggested a causal link between DRT and subsequent stroke in about half the patients with DRT because their strokes occurred within a month following DRT diagnosis.

Despite these findings, a majority – 74% – of patients with an identified DRT did not have a stroke, and 87% of the strokes that occurred in the patients who received the Watchman device occurred in the absence of a DRT, reported Dr. Reddy, who presented the findings at the meeting.

The most immediate implication of the findings is the strong case they make for rethinking the timing of planned follow-up transesophageal echocardiography (TEE) examinations of patients after they receive a Watchman device. The current, standard protocol schedules a TEE at 45 days after Watchman placement, when routine anticoagulation usually stops, and then a second TEE 12 months after placement. A better schedule might be to perform the first TEE 3-4 months after Watchman placement to give a potential DRT time to form once oral anticoagulant therapy stops, suggested Dr. Reddy, professor and director of the cardiac arrhythmia service at Mount Sinai Hospital and Health System in New York.

“Surveillance is very important. I don’t think DRT usually occurs unless anticoagulation is suboptimal or stops.” Dr. Reddy noted that he and his associates are analyzing the best time for TEE surveillance in other large databases of patients treated with left atrial appendage (LAA) closure. Newer models of LAA closure devices structurally modified to reduce thrombus formation are nearing clinical use, he added.

The analysis, believed to be the largest to date of DRT following left atrial appendage closure, was based on prospective data from four clinical trials. That included two randomized controlled trials, PROTECT AF and PREVAIL, as well as the CAP and CAP2 prospective registries.

Among 1,739 patients in those studies receiving an implant, 65 (3.74%) had DRT, the investigators found.

Over 1 year of follow-up, 25% of patients with DRT had an ischemic stroke or systemic embolism, versus 6.8% of patients without DRTs (P less than .001), they reported. That worked out to an event rate of 6.28 and 1.65 events per 100 patient years, respectively.

The strongest predictors of DRT in multivariable analysis included vascular disease, history of stroke or transient ischemic attack, permanent atrial fibrillation, and left atrial appendage diameter, according to the report. Conversely, increasing left ventricular ejection fraction was protective against DRT.

Taken together, these data support reevaluating the transesophageal echocardiography strategy, according to Dr. Reddy and his coauthors. Those approaches might include targeting patients with DRT risk factors, routine additional surveillance at 6 months, or delaying the first transesophageal echocardiography to 4 months.

“Importantly, none of these strategies have been rigorously compared, so these suggestions are subject to future studies,” the researchers wrote.

“DRT remains a problem despite increased operator experience with LAA occlusion and improved occluding devices,” commented David B. De Lurgio, MD, a cardiac electrophysiologist at Emory Healthcare in Atlanta. “What is a little alarming is that the risk for DRT extends beyond the period of prescribed anticoagulation. Although the risk from DRT mitigates the benefit of LAA closure compared with warfarin, it does not mitigate the benefit from occlusion compared with no treatment,” said Dr. De Lurgio, designated discussant for the report. “Prevention and management of DRT may require that each patient receive a tailored regimen of anticoagulation and surveillance.”

The Watchman studies were funded by Boston Scientific, the company that markets the device. Dr. Reddy has been a consultant to and has received research funding from Boston Scientific and from Abbott and Biosense-Webster, and he reported having an equity interest in Javelin and Surecor. Coauthors reported disclosures related to Boston Scientific, Johnson & Johnson, Abbott, and other medical device companies. Dr. De Lurgio has been a consultant to Boston Scientific.

Updated, 5/17/18: This article has been updated with reporting from Mitchel L. Zoler at the meeting, and has been revised for clarity and to reflect that the results were presented by Dr. Reddy.

SOURCE: Dukkipati SR et al. Circulation. 2018 May 11. doi: 10.1161/CIRCULATIONAHA.118.035090.

BOSTON – Device-related thrombus (DRT) does not occur often after left atrial appendage closure with the Watchman device. When it does, however, it is associated with a significantly higher rate of stroke and systemic embolism compared with that of patients with no DRT, according to a recent analysis presented at the annual scientific sessions of the Heart Rhythm Society.

Courtesy Boston Scientific

Given the negative implications of DRT, a judicious surveillance strategy should be considered, especially when DRT risk factors are present, investigators said in a report on the study, which was published simultaneously in Circulation.

“Certainly, DRT is associated with an increased risk of stroke, and therapeutic anticoagulation should be resumed when discovered with rigorous transesophageal echocardiography follow-up to ensure resolution,” noted senior investigator Vivek Y. Reddy, MD.

Despite the higher rates of all strokes, ischemic strokes, and hemorrhagic strokes linked with DRT, the complication did not link with a higher rate of all-cause mortality compared with patients who never had a DRT. The results also suggested a causal link between DRT and subsequent stroke in about half the patients with DRT because their strokes occurred within a month following DRT diagnosis.

Despite these findings, a majority – 74% – of patients with an identified DRT did not have a stroke, and 87% of the strokes that occurred in the patients who received the Watchman device occurred in the absence of a DRT, reported Dr. Reddy, who presented the findings at the meeting.

The most immediate implication of the findings is the strong case they make for rethinking the timing of planned follow-up transesophageal echocardiography (TEE) examinations of patients after they receive a Watchman device. The current, standard protocol schedules a TEE at 45 days after Watchman placement, when routine anticoagulation usually stops, and then a second TEE 12 months after placement. A better schedule might be to perform the first TEE 3-4 months after Watchman placement to give a potential DRT time to form once oral anticoagulant therapy stops, suggested Dr. Reddy, professor and director of the cardiac arrhythmia service at Mount Sinai Hospital and Health System in New York.

“Surveillance is very important. I don’t think DRT usually occurs unless anticoagulation is suboptimal or stops.” Dr. Reddy noted that he and his associates are analyzing the best time for TEE surveillance in other large databases of patients treated with left atrial appendage (LAA) closure. Newer models of LAA closure devices structurally modified to reduce thrombus formation are nearing clinical use, he added.

The analysis, believed to be the largest to date of DRT following left atrial appendage closure, was based on prospective data from four clinical trials. That included two randomized controlled trials, PROTECT AF and PREVAIL, as well as the CAP and CAP2 prospective registries.

Among 1,739 patients in those studies receiving an implant, 65 (3.74%) had DRT, the investigators found.

Over 1 year of follow-up, 25% of patients with DRT had an ischemic stroke or systemic embolism, versus 6.8% of patients without DRTs (P less than .001), they reported. That worked out to an event rate of 6.28 and 1.65 events per 100 patient years, respectively.

The strongest predictors of DRT in multivariable analysis included vascular disease, history of stroke or transient ischemic attack, permanent atrial fibrillation, and left atrial appendage diameter, according to the report. Conversely, increasing left ventricular ejection fraction was protective against DRT.

Taken together, these data support reevaluating the transesophageal echocardiography strategy, according to Dr. Reddy and his coauthors. Those approaches might include targeting patients with DRT risk factors, routine additional surveillance at 6 months, or delaying the first transesophageal echocardiography to 4 months.

“Importantly, none of these strategies have been rigorously compared, so these suggestions are subject to future studies,” the researchers wrote.

“DRT remains a problem despite increased operator experience with LAA occlusion and improved occluding devices,” commented David B. De Lurgio, MD, a cardiac electrophysiologist at Emory Healthcare in Atlanta. “What is a little alarming is that the risk for DRT extends beyond the period of prescribed anticoagulation. Although the risk from DRT mitigates the benefit of LAA closure compared with warfarin, it does not mitigate the benefit from occlusion compared with no treatment,” said Dr. De Lurgio, designated discussant for the report. “Prevention and management of DRT may require that each patient receive a tailored regimen of anticoagulation and surveillance.”

The Watchman studies were funded by Boston Scientific, the company that markets the device. Dr. Reddy has been a consultant to and has received research funding from Boston Scientific and from Abbott and Biosense-Webster, and he reported having an equity interest in Javelin and Surecor. Coauthors reported disclosures related to Boston Scientific, Johnson & Johnson, Abbott, and other medical device companies. Dr. De Lurgio has been a consultant to Boston Scientific.

Updated, 5/17/18: This article has been updated with reporting from Mitchel L. Zoler at the meeting, and has been revised for clarity and to reflect that the results were presented by Dr. Reddy.

SOURCE: Dukkipati SR et al. Circulation. 2018 May 11. doi: 10.1161/CIRCULATIONAHA.118.035090.

BOSTON – Device-related thrombus (DRT) does not occur often after left atrial appendage closure with the Watchman device. When it does, however, it is associated with a significantly higher rate of stroke and systemic embolism compared with that of patients with no DRT, according to a recent analysis presented at the annual scientific sessions of the Heart Rhythm Society.

Courtesy Boston Scientific

Given the negative implications of DRT, a judicious surveillance strategy should be considered, especially when DRT risk factors are present, investigators said in a report on the study, which was published simultaneously in Circulation.

“Certainly, DRT is associated with an increased risk of stroke, and therapeutic anticoagulation should be resumed when discovered with rigorous transesophageal echocardiography follow-up to ensure resolution,” noted senior investigator Vivek Y. Reddy, MD.

Despite the higher rates of all strokes, ischemic strokes, and hemorrhagic strokes linked with DRT, the complication did not link with a higher rate of all-cause mortality compared with patients who never had a DRT. The results also suggested a causal link between DRT and subsequent stroke in about half the patients with DRT because their strokes occurred within a month following DRT diagnosis.

Despite these findings, a majority – 74% – of patients with an identified DRT did not have a stroke, and 87% of the strokes that occurred in the patients who received the Watchman device occurred in the absence of a DRT, reported Dr. Reddy, who presented the findings at the meeting.

The most immediate implication of the findings is the strong case they make for rethinking the timing of planned follow-up transesophageal echocardiography (TEE) examinations of patients after they receive a Watchman device. The current, standard protocol schedules a TEE at 45 days after Watchman placement, when routine anticoagulation usually stops, and then a second TEE 12 months after placement. A better schedule might be to perform the first TEE 3-4 months after Watchman placement to give a potential DRT time to form once oral anticoagulant therapy stops, suggested Dr. Reddy, professor and director of the cardiac arrhythmia service at Mount Sinai Hospital and Health System in New York.

“Surveillance is very important. I don’t think DRT usually occurs unless anticoagulation is suboptimal or stops.” Dr. Reddy noted that he and his associates are analyzing the best time for TEE surveillance in other large databases of patients treated with left atrial appendage (LAA) closure. Newer models of LAA closure devices structurally modified to reduce thrombus formation are nearing clinical use, he added.

The analysis, believed to be the largest to date of DRT following left atrial appendage closure, was based on prospective data from four clinical trials. That included two randomized controlled trials, PROTECT AF and PREVAIL, as well as the CAP and CAP2 prospective registries.

Among 1,739 patients in those studies receiving an implant, 65 (3.74%) had DRT, the investigators found.

Over 1 year of follow-up, 25% of patients with DRT had an ischemic stroke or systemic embolism, versus 6.8% of patients without DRTs (P less than .001), they reported. That worked out to an event rate of 6.28 and 1.65 events per 100 patient years, respectively.

The strongest predictors of DRT in multivariable analysis included vascular disease, history of stroke or transient ischemic attack, permanent atrial fibrillation, and left atrial appendage diameter, according to the report. Conversely, increasing left ventricular ejection fraction was protective against DRT.

Taken together, these data support reevaluating the transesophageal echocardiography strategy, according to Dr. Reddy and his coauthors. Those approaches might include targeting patients with DRT risk factors, routine additional surveillance at 6 months, or delaying the first transesophageal echocardiography to 4 months.

“Importantly, none of these strategies have been rigorously compared, so these suggestions are subject to future studies,” the researchers wrote.

“DRT remains a problem despite increased operator experience with LAA occlusion and improved occluding devices,” commented David B. De Lurgio, MD, a cardiac electrophysiologist at Emory Healthcare in Atlanta. “What is a little alarming is that the risk for DRT extends beyond the period of prescribed anticoagulation. Although the risk from DRT mitigates the benefit of LAA closure compared with warfarin, it does not mitigate the benefit from occlusion compared with no treatment,” said Dr. De Lurgio, designated discussant for the report. “Prevention and management of DRT may require that each patient receive a tailored regimen of anticoagulation and surveillance.”

The Watchman studies were funded by Boston Scientific, the company that markets the device. Dr. Reddy has been a consultant to and has received research funding from Boston Scientific and from Abbott and Biosense-Webster, and he reported having an equity interest in Javelin and Surecor. Coauthors reported disclosures related to Boston Scientific, Johnson & Johnson, Abbott, and other medical device companies. Dr. De Lurgio has been a consultant to Boston Scientific.

Updated, 5/17/18: This article has been updated with reporting from Mitchel L. Zoler at the meeting, and has been revised for clarity and to reflect that the results were presented by Dr. Reddy.

SOURCE: Dukkipati SR et al. Circulation. 2018 May 11. doi: 10.1161/CIRCULATIONAHA.118.035090.

Third-trimester exposure to airborne particulate matter (PM) smaller than 2.5 mcm in size (PM_2.5) has been linked to higher levels of systolic blood pressure during childhood.

Mingyu Zhang of Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates found that the highest tertile exposure was tied to an increased likelihood of childhood elevated BP, defined as systolic blood pressure higher than the 90^th percentile, compared with those in the lowest tertile (relative risk, 1.60; 95% confidence interval, 1.12-2.27).

Previous studies have shown a relationship between exposure to PM_2.5and elevated BP in children and adults. Mouse models suggest that PM_2.5 may interfere with in utero development of the cardiovascular system. One previous study found evidence that third-trimester exposure to PM_2.5was linked to heightened BP in newborns, while a retrospective analysis showed no association with BP in adolescents.

Copyright fotolia

Further analysis suggested that 35% of the association between exposure and elevated BP risk was mediated by birth weight and BMI z score during childhood. When these factors were added to the models, the association between PM exposure and BP risk was no longer significant.

Although the findings are intriguing, they cannot prove causation, according to the researchers.

The study was funded by the National Institutes of Health and the Maternal and Child Health Bureau. Dr. Gold and Dr. Zanobetti have received funding from NIH.

SOURCE: Zhang et al. 2018 Jul. doi: 10.1161/hypertensionaha.117.10944.

Third-trimester exposure to airborne particulate matter (PM) smaller than 2.5 mcm in size (PM_2.5) has been linked to higher levels of systolic blood pressure during childhood.

Mingyu Zhang of Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates found that the highest tertile exposure was tied to an increased likelihood of childhood elevated BP, defined as systolic blood pressure higher than the 90^th percentile, compared with those in the lowest tertile (relative risk, 1.60; 95% confidence interval, 1.12-2.27).

Previous studies have shown a relationship between exposure to PM_2.5and elevated BP in children and adults. Mouse models suggest that PM_2.5 may interfere with in utero development of the cardiovascular system. One previous study found evidence that third-trimester exposure to PM_2.5was linked to heightened BP in newborns, while a retrospective analysis showed no association with BP in adolescents.

Copyright fotolia

Further analysis suggested that 35% of the association between exposure and elevated BP risk was mediated by birth weight and BMI z score during childhood. When these factors were added to the models, the association between PM exposure and BP risk was no longer significant.

Although the findings are intriguing, they cannot prove causation, according to the researchers.

The study was funded by the National Institutes of Health and the Maternal and Child Health Bureau. Dr. Gold and Dr. Zanobetti have received funding from NIH.

SOURCE: Zhang et al. 2018 Jul. doi: 10.1161/hypertensionaha.117.10944.

Third-trimester exposure to airborne particulate matter (PM) smaller than 2.5 mcm in size (PM_2.5) has been linked to higher levels of systolic blood pressure during childhood.

Mingyu Zhang of Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates found that the highest tertile exposure was tied to an increased likelihood of childhood elevated BP, defined as systolic blood pressure higher than the 90^th percentile, compared with those in the lowest tertile (relative risk, 1.60; 95% confidence interval, 1.12-2.27).

Previous studies have shown a relationship between exposure to PM_2.5and elevated BP in children and adults. Mouse models suggest that PM_2.5 may interfere with in utero development of the cardiovascular system. One previous study found evidence that third-trimester exposure to PM_2.5was linked to heightened BP in newborns, while a retrospective analysis showed no association with BP in adolescents.

Copyright fotolia

Further analysis suggested that 35% of the association between exposure and elevated BP risk was mediated by birth weight and BMI z score during childhood. When these factors were added to the models, the association between PM exposure and BP risk was no longer significant.

Although the findings are intriguing, they cannot prove causation, according to the researchers.

The study was funded by the National Institutes of Health and the Maternal and Child Health Bureau. Dr. Gold and Dr. Zanobetti have received funding from NIH.

SOURCE: Zhang et al. 2018 Jul. doi: 10.1161/hypertensionaha.117.10944.

Phlegmasia cerulea dolens (PCD), a life-threatening complication of deep venous thrombosis (DVT), is characterized by massive iliofemoral thrombus that extends to the collateral veins, leading to fluid sequestration and elevated compartment pressures that ultimately compromise arterial flow. Phlegmasia cerulea dolens can rapidly progress to compartment syndrome and gangrene.^1,2 The affected limbs of patients with PCD can be hypoxic and appear purple in color due to substantial lack of blood flow, with diminished or absent pulses. Risk factors for PCD include malignancy, hypercoagulable states, venous stasis, contraceptive agents, inferior vena cava (IVC) filter, aneurysm, history of DVT, trauma, heparin-induced thrombocytopenia, femoral vein catheterization, antiphospholipid syndrome, or pregnancy.^3-6 Failure to treat PCD early and aggressively carries an amputation rate of up to 50% and a mortality rate of up to 40%.⁴

We present the case of a patient with PCD, whose condition rapidly deteriorated despite prompt diagnosis and treatment.

Case

A 58-year-old woman presented to the ED with a 1-day history of back and leg pain and difficulty walking. When asked about the severity of her pain, she rated her leg pain at 10 on a scale of 0 to 10. The patient’s history was significant for DVT and pulmonary embolism (PE), for which a Greenfield IVC had been placed and for which she was on prophylactic warfarin therapy. The patient stated that she had been taken off warfarin several weeks prior to presentation in preparation for an elective colonoscopy and dental procedure, but had restarted the warfarin therapy 2 days prior to presentation. She had no history of diabetes mellitus or renal disease.

Initial vital signs at presentation were: blood pressure, 120/91 mm Hg; heart rate, 110 beats/min; respiratory rate, 24 breaths/min; and temperature, 96.6°F. Oxygen saturation was 100% on a nonrebreather mask.

On examination, the patient was alert and oriented to person, time, and place, but appeared dyspneic. An electrocardiogram revealed sinus tachycardia. On physical examination, lung sounds were clear to auscultation bilaterally with good air movement, and the abdomen was soft and nontender with normal bowel sounds. The dorsalis pedis and posterior tibial pulses were absent bilaterally, lower extremity capillary refill was 3 seconds, and the legs appeared mildly erythematous and cool to touch. No speech or neurological deficits were present.

Laboratory evaluation was remarkable for metabolic acidosis, venous pH, 7.11; bicarbonate, 11.7; partial pressure of carbon dioxide, 37.6; lactic acid, 8.8 mEq/L leukocytosis, 24,900 u/L; glucose, 296 mg/dL; creatinine, 2.41 mg/dL; and international normalized ratio, 1.36.

Before additional laboratory studies and imaging could be obtained, the patient developed altered mental status, hypotension, and paralysis of the lower extremities. She was orally intubated for airway protection and was given a total of 4 L of normal saline intravenously (IV) for hypotension and acidosis; sodium bicarbonate for metabolic acidosis; norepinephrine for hypotension; fentanyl for pain; and ondansetron for nausea. A central line and arterial line were placed for administering medication and hemodynamic monitoring.

Discussion

This case illustrates the severity and complications of PCD and the rapidity with which this condition can deteriorate. At the time of ED presentation, the patient had already developed bilateral PCD, metabolic acidosis, and bilateral PE. Unfortunately, due to decreased venous return, decreased cardiac output, and severe shock, she quickly became unstable and progressed rapidly to multisystem organ failure leading to death.

Risk Factors

A prior patient history DVT and an IVC filter are both significant risk factors for the progression of DVT to PCD;^3,6 however, in this case, IVC filter failed to prevent emboli from reaching the lungs. Extensive thrombi led to severely decreased venous return and cardiac output, causing life-threatening shock, ischemia, and metabolic acidosis. A lactic acid level taken on hospital day 2 was elevated at 19 mEq/L, demonstrating the severity, morbidity, and progression of PCD.

Signs and Symptoms

The three cardinal signs that lead to a clinical diagnosis of PCD are edema, pain, and violaceous discoloration or skin mottling.³ Although most commonly found in the lower extremity, PCD can occur in any limb due to occlusion of venous outflow.⁷ Unfortunately, a clinical diagnosis of PCD is not often made until the venous occlusion becomes severe enough to impair arterial flow and cause venous gangrene, tissue ischemia, shock, and death.⁸

Although IVC filters are designed to prevent life-threatening PE, there are risk factors associated with their use. Whether placed recently or decades prior, urgent investigation, such as immediate CT scan, should be undertaken in patients presenting with DVT-like symptoms who have a history of an IVC filter, to ensure the filter has not shifted from its original placement and is not occluding the IVC.

Conclusion

Phlegmasia cerulea dolens is an uncommon vascular emergency, but one that has a high-morbidity and high-mortality rate. This case demonstrates the importance of early diagnosis, aggressive treatment, and the severe complications that can develop in PCD.

There are cases in the literature where patients diagnosed with PCD had a successful outcome with pharmacological or surgical intervention such as thrombectomy. Treatment for PCD is most effective when instituted early in onset. As seen in our patient, the tendency for rapid deterioration in PCD can limit potentially lifesaving therapeutic options, decreasing the chances of a successful outcome. Emergency physicians, therefore, must be aware of the high-mortality rate associated with this disorder and the possibility of rapid progression from stable to critical condition.

Phlegmasia cerulea dolens (PCD), a life-threatening complication of deep venous thrombosis (DVT), is characterized by massive iliofemoral thrombus that extends to the collateral veins, leading to fluid sequestration and elevated compartment pressures that ultimately compromise arterial flow. Phlegmasia cerulea dolens can rapidly progress to compartment syndrome and gangrene.^1,2 The affected limbs of patients with PCD can be hypoxic and appear purple in color due to substantial lack of blood flow, with diminished or absent pulses. Risk factors for PCD include malignancy, hypercoagulable states, venous stasis, contraceptive agents, inferior vena cava (IVC) filter, aneurysm, history of DVT, trauma, heparin-induced thrombocytopenia, femoral vein catheterization, antiphospholipid syndrome, or pregnancy.^3-6 Failure to treat PCD early and aggressively carries an amputation rate of up to 50% and a mortality rate of up to 40%.⁴

We present the case of a patient with PCD, whose condition rapidly deteriorated despite prompt diagnosis and treatment.

Case

A 58-year-old woman presented to the ED with a 1-day history of back and leg pain and difficulty walking. When asked about the severity of her pain, she rated her leg pain at 10 on a scale of 0 to 10. The patient’s history was significant for DVT and pulmonary embolism (PE), for which a Greenfield IVC had been placed and for which she was on prophylactic warfarin therapy. The patient stated that she had been taken off warfarin several weeks prior to presentation in preparation for an elective colonoscopy and dental procedure, but had restarted the warfarin therapy 2 days prior to presentation. She had no history of diabetes mellitus or renal disease.

Initial vital signs at presentation were: blood pressure, 120/91 mm Hg; heart rate, 110 beats/min; respiratory rate, 24 breaths/min; and temperature, 96.6°F. Oxygen saturation was 100% on a nonrebreather mask.

On examination, the patient was alert and oriented to person, time, and place, but appeared dyspneic. An electrocardiogram revealed sinus tachycardia. On physical examination, lung sounds were clear to auscultation bilaterally with good air movement, and the abdomen was soft and nontender with normal bowel sounds. The dorsalis pedis and posterior tibial pulses were absent bilaterally, lower extremity capillary refill was 3 seconds, and the legs appeared mildly erythematous and cool to touch. No speech or neurological deficits were present.

Laboratory evaluation was remarkable for metabolic acidosis, venous pH, 7.11; bicarbonate, 11.7; partial pressure of carbon dioxide, 37.6; lactic acid, 8.8 mEq/L leukocytosis, 24,900 u/L; glucose, 296 mg/dL; creatinine, 2.41 mg/dL; and international normalized ratio, 1.36.

Before additional laboratory studies and imaging could be obtained, the patient developed altered mental status, hypotension, and paralysis of the lower extremities. She was orally intubated for airway protection and was given a total of 4 L of normal saline intravenously (IV) for hypotension and acidosis; sodium bicarbonate for metabolic acidosis; norepinephrine for hypotension; fentanyl for pain; and ondansetron for nausea. A central line and arterial line were placed for administering medication and hemodynamic monitoring.

Discussion

This case illustrates the severity and complications of PCD and the rapidity with which this condition can deteriorate. At the time of ED presentation, the patient had already developed bilateral PCD, metabolic acidosis, and bilateral PE. Unfortunately, due to decreased venous return, decreased cardiac output, and severe shock, she quickly became unstable and progressed rapidly to multisystem organ failure leading to death.

Risk Factors

A prior patient history DVT and an IVC filter are both significant risk factors for the progression of DVT to PCD;^3,6 however, in this case, IVC filter failed to prevent emboli from reaching the lungs. Extensive thrombi led to severely decreased venous return and cardiac output, causing life-threatening shock, ischemia, and metabolic acidosis. A lactic acid level taken on hospital day 2 was elevated at 19 mEq/L, demonstrating the severity, morbidity, and progression of PCD.

Signs and Symptoms

The three cardinal signs that lead to a clinical diagnosis of PCD are edema, pain, and violaceous discoloration or skin mottling.³ Although most commonly found in the lower extremity, PCD can occur in any limb due to occlusion of venous outflow.⁷ Unfortunately, a clinical diagnosis of PCD is not often made until the venous occlusion becomes severe enough to impair arterial flow and cause venous gangrene, tissue ischemia, shock, and death.⁸

Although IVC filters are designed to prevent life-threatening PE, there are risk factors associated with their use. Whether placed recently or decades prior, urgent investigation, such as immediate CT scan, should be undertaken in patients presenting with DVT-like symptoms who have a history of an IVC filter, to ensure the filter has not shifted from its original placement and is not occluding the IVC.

Conclusion

Phlegmasia cerulea dolens is an uncommon vascular emergency, but one that has a high-morbidity and high-mortality rate. This case demonstrates the importance of early diagnosis, aggressive treatment, and the severe complications that can develop in PCD.

There are cases in the literature where patients diagnosed with PCD had a successful outcome with pharmacological or surgical intervention such as thrombectomy. Treatment for PCD is most effective when instituted early in onset. As seen in our patient, the tendency for rapid deterioration in PCD can limit potentially lifesaving therapeutic options, decreasing the chances of a successful outcome. Emergency physicians, therefore, must be aware of the high-mortality rate associated with this disorder and the possibility of rapid progression from stable to critical condition.

Phlegmasia cerulea dolens (PCD), a life-threatening complication of deep venous thrombosis (DVT), is characterized by massive iliofemoral thrombus that extends to the collateral veins, leading to fluid sequestration and elevated compartment pressures that ultimately compromise arterial flow. Phlegmasia cerulea dolens can rapidly progress to compartment syndrome and gangrene.^1,2 The affected limbs of patients with PCD can be hypoxic and appear purple in color due to substantial lack of blood flow, with diminished or absent pulses. Risk factors for PCD include malignancy, hypercoagulable states, venous stasis, contraceptive agents, inferior vena cava (IVC) filter, aneurysm, history of DVT, trauma, heparin-induced thrombocytopenia, femoral vein catheterization, antiphospholipid syndrome, or pregnancy.^3-6 Failure to treat PCD early and aggressively carries an amputation rate of up to 50% and a mortality rate of up to 40%.⁴

We present the case of a patient with PCD, whose condition rapidly deteriorated despite prompt diagnosis and treatment.

Case

A 58-year-old woman presented to the ED with a 1-day history of back and leg pain and difficulty walking. When asked about the severity of her pain, she rated her leg pain at 10 on a scale of 0 to 10. The patient’s history was significant for DVT and pulmonary embolism (PE), for which a Greenfield IVC had been placed and for which she was on prophylactic warfarin therapy. The patient stated that she had been taken off warfarin several weeks prior to presentation in preparation for an elective colonoscopy and dental procedure, but had restarted the warfarin therapy 2 days prior to presentation. She had no history of diabetes mellitus or renal disease.

Initial vital signs at presentation were: blood pressure, 120/91 mm Hg; heart rate, 110 beats/min; respiratory rate, 24 breaths/min; and temperature, 96.6°F. Oxygen saturation was 100% on a nonrebreather mask.

On examination, the patient was alert and oriented to person, time, and place, but appeared dyspneic. An electrocardiogram revealed sinus tachycardia. On physical examination, lung sounds were clear to auscultation bilaterally with good air movement, and the abdomen was soft and nontender with normal bowel sounds. The dorsalis pedis and posterior tibial pulses were absent bilaterally, lower extremity capillary refill was 3 seconds, and the legs appeared mildly erythematous and cool to touch. No speech or neurological deficits were present.

Laboratory evaluation was remarkable for metabolic acidosis, venous pH, 7.11; bicarbonate, 11.7; partial pressure of carbon dioxide, 37.6; lactic acid, 8.8 mEq/L leukocytosis, 24,900 u/L; glucose, 296 mg/dL; creatinine, 2.41 mg/dL; and international normalized ratio, 1.36.

Before additional laboratory studies and imaging could be obtained, the patient developed altered mental status, hypotension, and paralysis of the lower extremities. She was orally intubated for airway protection and was given a total of 4 L of normal saline intravenously (IV) for hypotension and acidosis; sodium bicarbonate for metabolic acidosis; norepinephrine for hypotension; fentanyl for pain; and ondansetron for nausea. A central line and arterial line were placed for administering medication and hemodynamic monitoring.

Discussion

This case illustrates the severity and complications of PCD and the rapidity with which this condition can deteriorate. At the time of ED presentation, the patient had already developed bilateral PCD, metabolic acidosis, and bilateral PE. Unfortunately, due to decreased venous return, decreased cardiac output, and severe shock, she quickly became unstable and progressed rapidly to multisystem organ failure leading to death.

Risk Factors

A prior patient history DVT and an IVC filter are both significant risk factors for the progression of DVT to PCD;^3,6 however, in this case, IVC filter failed to prevent emboli from reaching the lungs. Extensive thrombi led to severely decreased venous return and cardiac output, causing life-threatening shock, ischemia, and metabolic acidosis. A lactic acid level taken on hospital day 2 was elevated at 19 mEq/L, demonstrating the severity, morbidity, and progression of PCD.

Signs and Symptoms

The three cardinal signs that lead to a clinical diagnosis of PCD are edema, pain, and violaceous discoloration or skin mottling.³ Although most commonly found in the lower extremity, PCD can occur in any limb due to occlusion of venous outflow.⁷ Unfortunately, a clinical diagnosis of PCD is not often made until the venous occlusion becomes severe enough to impair arterial flow and cause venous gangrene, tissue ischemia, shock, and death.⁸

Although IVC filters are designed to prevent life-threatening PE, there are risk factors associated with their use. Whether placed recently or decades prior, urgent investigation, such as immediate CT scan, should be undertaken in patients presenting with DVT-like symptoms who have a history of an IVC filter, to ensure the filter has not shifted from its original placement and is not occluding the IVC.

Conclusion

Phlegmasia cerulea dolens is an uncommon vascular emergency, but one that has a high-morbidity and high-mortality rate. This case demonstrates the importance of early diagnosis, aggressive treatment, and the severe complications that can develop in PCD.

There are cases in the literature where patients diagnosed with PCD had a successful outcome with pharmacological or surgical intervention such as thrombectomy. Treatment for PCD is most effective when instituted early in onset. As seen in our patient, the tendency for rapid deterioration in PCD can limit potentially lifesaving therapeutic options, decreasing the chances of a successful outcome. Emergency physicians, therefore, must be aware of the high-mortality rate associated with this disorder and the possibility of rapid progression from stable to critical condition.

Facial paralysis is a common medical complaint—one that has fascinated ancient and contemporary physicians alike.¹ An idiopathic facial nerve paresis involving the lower motor neuron was described in 1821 by Sir Charles Bell. This entity became known as a Bell’s palsy, the hallmark of which was weakness or complete paralysis of the muscles of one side of the face, with no sparing of the muscles of the forehead. However, not all facial paralysis is due to Bell’s palsy.

We present a case of a patient with a Bell’s palsy mimic to facilitate and guide the differential diagnosis and distinguish conditions from the classical presentation that Bell first described to the more concerning symptoms that may not be immediately obvious. Our case further underscores the importance of performing a thorough assessment to determine the presence of other neurological findings.

Case

A 61-year-old woman presented to the ED for evaluation of right facial droop and sensation of “room spinning.” The patient stated both symptoms began approximately 36 hours prior to presentation, upon awakening. She further noted that the right side of her face felt “funny” and numb.

The patient denied any headache, neck or chest pain, extremity numbness, or weakness, but stated that she felt like she was going to fall toward her right side whenever she attempted to walk. The patient’s medical history was significant for hypertension, for which she was taking losartan. Her surgical history was notable for a left oophorectomy secondary to an ovarian cyst. Regarding the social history, the patient admitted to smoking 90 packs of cigarettes per year, but denied alcohol or illicit drug use.

Upon arrival at the ED, the patient’s vital signs were: blood pressure, 164/86 mm Hg: pulse, 89 beats/min; respiratory rate, 18 breaths/min; and temperature, 98.6°F. Oxygen saturation was 98% on room air.

Physical examination revealed the patient had a right facial droop consistent with right facial palsy. She was unable to wrinkle her right forehead or fully close her right eye. There were no field cuts on confrontation. The patient’s speech was noticeable for a mild dysarthria. The motor examination revealed mild weakness of the left upper extremity and impaired right facial sensation. There were no rashes noted on the face, head, or ears. The patient had slightly impaired hearing in the right ear, which was new in onset. The remainder of the physical examination was unremarkable.

Although the patient exhibited the classic signs of Bell’s palsy, including complete paralysis of the muscles of one side of the face, inability to wrinkle the muscle of the right forehead, and inability to fully close the right eye, she also had concerning symptoms of vertigo, dysarthria, and contralateral upper extremity weakness.

A computed tomography (CT) scan of the head was ordered, which revealed a large mass lesion centered in the right petrous apex, with an associated large component extending medially into the right cerebellopontine angle (CPA) that caused a mass effect on the adjacent brainstem (Figures 1a and 1b).

Discussion

Accounts of facial paralysis and facial nerve disorders have been noted throughout history and include accounts of the condition by Hippocrates.¹ Bell’s palsy was named after surgeon Sir Charles Bell, who described a peripheral-nerve paralysis of the facial nerve in 1821. Bell’s work helped to elucidate the anatomy and functional role of the facial nerve.^1,2

Signs and Symptoms

The classic presentation of Bell’s palsy is weakness or complete paralysis of the muscles of one side of the face, with no sparing of the muscles of the forehead. The eyelid on the affected side generally does not close, which can result in ocular irritation due to ineffective lubrication.

A scoring system has been developed by House and Brackmann which grades the degree impairment based on such characteristics as facial muscle function and eye closure.^3,4 Approximately 96% of patients with a Bell’s palsy will improve to a House-Brackmann score of 2 or better within 1 year from diagnosis,⁵ and 85% of patients with Bell’s palsy will show at least some improvement within 3 weeks of onset (Table).² Although the classic description of Bell’s palsy notes the condition as idiopathic, there is an increasing body of evidence in the literature showing a link to herpes simplex virus 1.^5-7

Ramsey-Hunt Syndrome

The relationship between Bell’s palsy and Ramsey-Hunt syndrome is complex and controversial. Ramsey-Hunt syndrome is a constellation of possible complications from varicella-virus infection. Symptoms of Ramsey-Hunt syndrome include facial paralysis, tinnitus, hearing loss, vertigo, hyperacusis (increased sensitivity to certain frequencies and volume ranges of sound), and decreased ocular tearing.⁸ Due to the nature of symptoms associated with Ramsey-Hunt syndrome, it is apparent that the condition involves more than the seventh cranial nerve. In fact, studies have shown that Ramsey-Hunt syndrome can affect the fifth, sixth, eighth, and ninth cranial nerves.⁸

Ramsey-Hunt syndrome, which can present in the absence of cutaneous rash (referred to as zoster sine herpete), is estimated to occur in 8% to 20% of unilateral facial nerve palsies in adult patients.^8,9 Regardless of the etiology of Bell’s palsy, a review of the literature makes it clear that facial nerve paralysis is not synonymous with Bell’s palsy.¹⁰ In one example, Yetter et al¹⁰ describe the case of a patient who, though initially diagnosed with Bell’s palsy, ultimately was found to have a facial palsy due to a parotid gland malignancy.

Likewise, Stomeo¹¹ describes a case of a patient with facial paralysis and profound ipsilateral hearing loss who ultimately was found to have a mucoepithelial carcinoma of the parotid gland. In their report, the authors note that approximately 80% of facial nerve paralysis is due to Bell’s palsy, while 5% is due to malignancy.

In another report, Clemis¹² describes a case in which a patient who initially was diagnosed with Bell’s palsy eventually was found to have an adenoid cystic carcinoma of the parotid. Thus, the authors appropriately emphasize in their report that “all that palsies is not Bell’s.”

Differential Diagnosis

Historical factors, including timing and duration of symptom onset, help to distinguish a Bell’s palsy from other disorders that can mimic this condition. In their study, Brach VanSwewaringen¹³ highlight the fact that “not all facial paralysis is Bell’s palsy.” In their review, the authors describe clues to help distinguish conditions that mimic Bell’s palsy. For example, maximal weakness from Bell’s Palsy typically occurs within 3 to 7 days from symptom onset, and that a more gradual onset of symptoms, with slow or negligible improvement over 6 to 12 months, is more indicative of a space-occupying lesion than Bell’s palsy.¹³It is, however, important to note that although the patient in our case had a central lesion, she experienced an acute onset of symptoms.

The presence of additional symptoms may also suggest an alternative diagnosis. Brach and VanSwearingen¹³ further noted that symptoms associated with the eighth nerve, such as vertigo, tinnitus, and hearing loss may be found in patients with a CPA tumor. In patients with larger tumors, ninth and 10th nerve symptoms, including the impaired hearing noted in our patient, may be present. Some patients with ninth and 10th nerve symptoms may perceive a sense of facial numbness, but actual sensory changes in the facial nerve distribution are unlikely in Bell’s palsy. Gustatory changes, however, are consistent with Bell’s palsy.

Ear pain is consistent with Bell’s palsy and is a signal to be vigilant for the possible emergence of an ear rash, which would suggest the diagnosis of herpes zoster oticus along the trajectory of Ramsey-Hunt syndrome. Facial pain in the area of the facial nerve is inconsistent with Bell’s palsy, while hyperacusis is consistent with Bell’s palsy. Hearing loss is an eighth nerve symptom that is inconsistent with Bell’s palsy.

Similarly, there are physical examination findings that can help distinguish a true Bell’s palsy from a mimic. Changes in tear production are consistent with Bell’s palsy, but imbalance and disequilibrium are not.¹⁴

As previously noted, the patient in this case had difficulty walking and felt as if she was falling toward her right side.

One way to organize the causes of facial paralysis has been proposed by Adour et al.¹⁵ In this system, etiologies are listed as either acute paralysis or chronic, progressive paralysis. Acute paralysis (ie, the sudden onset of symptoms with maximal severity within 2 weeks), of which Bell’s palsy is the most common, can be seen in cases of polyneuritis.

A new case of Bell’s palsy has been estimated to occur in the United States every 10 minutes.⁸ Guillain-Barré syndrome and Lyme disease are also in this category, as is Ramsey-Hunt syndrome. Patients with Lyme disease may have a history of a tick bite or rash.¹⁴

Trauma can also cause acute facial nerve paralysis (eg, blunt trauma-associated facial fracture, penetrating trauma, birth trauma). Unilateral central facial weakness can have a neurological cause, such as a lesion to the contralateral cortex, subcortical white matter, or internal capsule.^2,15 Otitis media can sometimes cause facial paralysis.¹⁶ A cholesteatoma can cause acute facial paralysis.² Malignancies cause 5% of all cases of facial paralysis. Primary parotid tumors of various types are in this category. Metastatic disease from breast, lung, skin, colon, and kidney may cause facial paralysis. As our case illustrates, CPA tumors can cause facial paralysis.¹⁵ It is important to also note that a patient can have both a Bell’s palsy and a concurrent disease. There are a number of case reports in the literature that describe acute onset of facial paralysis as a presenting symptom of malignancy.¹⁷ In addition, there are cases wherein a neurological finding on imaging, such as an acoustic neuroma, was presumed to be the cause of facial paralysis, yet the patient’s symptoms resolved in a manner consistent with Bell’s palsy.¹⁸

For example, Lagman et al¹⁹ described a patient in which a CPA lipoma was presumed to be the cause of the facial paralysis, but the eventual outcome showed the lipoma to have been an incidentaloma.

Conclusion

This case demonstrates a presenting symptom of facial palsy and the presence of a CPA tumor. The presence of vertigo along with other historical and physical examination findings inconsistent with Bell’s palsy prompted the CT scan of the head. A review of the literature suggests a number of important findings in patients with facial palsy to assist the clinician in distinguishing true Bell’s palsy from other diseases that can mimic this condition. This case serves as a reminder of the need to perform a thorough and diligent workup to determine the presence or absence of other neurologic findings prior to closing on the diagnosis of Bell’s palsy.

Facial paralysis is a common medical complaint—one that has fascinated ancient and contemporary physicians alike.¹ An idiopathic facial nerve paresis involving the lower motor neuron was described in 1821 by Sir Charles Bell. This entity became known as a Bell’s palsy, the hallmark of which was weakness or complete paralysis of the muscles of one side of the face, with no sparing of the muscles of the forehead. However, not all facial paralysis is due to Bell’s palsy.

We present a case of a patient with a Bell’s palsy mimic to facilitate and guide the differential diagnosis and distinguish conditions from the classical presentation that Bell first described to the more concerning symptoms that may not be immediately obvious. Our case further underscores the importance of performing a thorough assessment to determine the presence of other neurological findings.

Case

A 61-year-old woman presented to the ED for evaluation of right facial droop and sensation of “room spinning.” The patient stated both symptoms began approximately 36 hours prior to presentation, upon awakening. She further noted that the right side of her face felt “funny” and numb.

The patient denied any headache, neck or chest pain, extremity numbness, or weakness, but stated that she felt like she was going to fall toward her right side whenever she attempted to walk. The patient’s medical history was significant for hypertension, for which she was taking losartan. Her surgical history was notable for a left oophorectomy secondary to an ovarian cyst. Regarding the social history, the patient admitted to smoking 90 packs of cigarettes per year, but denied alcohol or illicit drug use.

Upon arrival at the ED, the patient’s vital signs were: blood pressure, 164/86 mm Hg: pulse, 89 beats/min; respiratory rate, 18 breaths/min; and temperature, 98.6°F. Oxygen saturation was 98% on room air.

Physical examination revealed the patient had a right facial droop consistent with right facial palsy. She was unable to wrinkle her right forehead or fully close her right eye. There were no field cuts on confrontation. The patient’s speech was noticeable for a mild dysarthria. The motor examination revealed mild weakness of the left upper extremity and impaired right facial sensation. There were no rashes noted on the face, head, or ears. The patient had slightly impaired hearing in the right ear, which was new in onset. The remainder of the physical examination was unremarkable.

Although the patient exhibited the classic signs of Bell’s palsy, including complete paralysis of the muscles of one side of the face, inability to wrinkle the muscle of the right forehead, and inability to fully close the right eye, she also had concerning symptoms of vertigo, dysarthria, and contralateral upper extremity weakness.

A computed tomography (CT) scan of the head was ordered, which revealed a large mass lesion centered in the right petrous apex, with an associated large component extending medially into the right cerebellopontine angle (CPA) that caused a mass effect on the adjacent brainstem (Figures 1a and 1b).

Discussion

Accounts of facial paralysis and facial nerve disorders have been noted throughout history and include accounts of the condition by Hippocrates.¹ Bell’s palsy was named after surgeon Sir Charles Bell, who described a peripheral-nerve paralysis of the facial nerve in 1821. Bell’s work helped to elucidate the anatomy and functional role of the facial nerve.^1,2

Signs and Symptoms

The classic presentation of Bell’s palsy is weakness or complete paralysis of the muscles of one side of the face, with no sparing of the muscles of the forehead. The eyelid on the affected side generally does not close, which can result in ocular irritation due to ineffective lubrication.

A scoring system has been developed by House and Brackmann which grades the degree impairment based on such characteristics as facial muscle function and eye closure.^3,4 Approximately 96% of patients with a Bell’s palsy will improve to a House-Brackmann score of 2 or better within 1 year from diagnosis,⁵ and 85% of patients with Bell’s palsy will show at least some improvement within 3 weeks of onset (Table).² Although the classic description of Bell’s palsy notes the condition as idiopathic, there is an increasing body of evidence in the literature showing a link to herpes simplex virus 1.^5-7

Ramsey-Hunt Syndrome

The relationship between Bell’s palsy and Ramsey-Hunt syndrome is complex and controversial. Ramsey-Hunt syndrome is a constellation of possible complications from varicella-virus infection. Symptoms of Ramsey-Hunt syndrome include facial paralysis, tinnitus, hearing loss, vertigo, hyperacusis (increased sensitivity to certain frequencies and volume ranges of sound), and decreased ocular tearing.⁸ Due to the nature of symptoms associated with Ramsey-Hunt syndrome, it is apparent that the condition involves more than the seventh cranial nerve. In fact, studies have shown that Ramsey-Hunt syndrome can affect the fifth, sixth, eighth, and ninth cranial nerves.⁸

Ramsey-Hunt syndrome, which can present in the absence of cutaneous rash (referred to as zoster sine herpete), is estimated to occur in 8% to 20% of unilateral facial nerve palsies in adult patients.^8,9 Regardless of the etiology of Bell’s palsy, a review of the literature makes it clear that facial nerve paralysis is not synonymous with Bell’s palsy.¹⁰ In one example, Yetter et al¹⁰ describe the case of a patient who, though initially diagnosed with Bell’s palsy, ultimately was found to have a facial palsy due to a parotid gland malignancy.

Likewise, Stomeo¹¹ describes a case of a patient with facial paralysis and profound ipsilateral hearing loss who ultimately was found to have a mucoepithelial carcinoma of the parotid gland. In their report, the authors note that approximately 80% of facial nerve paralysis is due to Bell’s palsy, while 5% is due to malignancy.

In another report, Clemis¹² describes a case in which a patient who initially was diagnosed with Bell’s palsy eventually was found to have an adenoid cystic carcinoma of the parotid. Thus, the authors appropriately emphasize in their report that “all that palsies is not Bell’s.”

Differential Diagnosis

Historical factors, including timing and duration of symptom onset, help to distinguish a Bell’s palsy from other disorders that can mimic this condition. In their study, Brach VanSwewaringen¹³ highlight the fact that “not all facial paralysis is Bell’s palsy.” In their review, the authors describe clues to help distinguish conditions that mimic Bell’s palsy. For example, maximal weakness from Bell’s Palsy typically occurs within 3 to 7 days from symptom onset, and that a more gradual onset of symptoms, with slow or negligible improvement over 6 to 12 months, is more indicative of a space-occupying lesion than Bell’s palsy.¹³It is, however, important to note that although the patient in our case had a central lesion, she experienced an acute onset of symptoms.

The presence of additional symptoms may also suggest an alternative diagnosis. Brach and VanSwearingen¹³ further noted that symptoms associated with the eighth nerve, such as vertigo, tinnitus, and hearing loss may be found in patients with a CPA tumor. In patients with larger tumors, ninth and 10th nerve symptoms, including the impaired hearing noted in our patient, may be present. Some patients with ninth and 10th nerve symptoms may perceive a sense of facial numbness, but actual sensory changes in the facial nerve distribution are unlikely in Bell’s palsy. Gustatory changes, however, are consistent with Bell’s palsy.

Ear pain is consistent with Bell’s palsy and is a signal to be vigilant for the possible emergence of an ear rash, which would suggest the diagnosis of herpes zoster oticus along the trajectory of Ramsey-Hunt syndrome. Facial pain in the area of the facial nerve is inconsistent with Bell’s palsy, while hyperacusis is consistent with Bell’s palsy. Hearing loss is an eighth nerve symptom that is inconsistent with Bell’s palsy.

Similarly, there are physical examination findings that can help distinguish a true Bell’s palsy from a mimic. Changes in tear production are consistent with Bell’s palsy, but imbalance and disequilibrium are not.¹⁴

As previously noted, the patient in this case had difficulty walking and felt as if she was falling toward her right side.

One way to organize the causes of facial paralysis has been proposed by Adour et al.¹⁵ In this system, etiologies are listed as either acute paralysis or chronic, progressive paralysis. Acute paralysis (ie, the sudden onset of symptoms with maximal severity within 2 weeks), of which Bell’s palsy is the most common, can be seen in cases of polyneuritis.

A new case of Bell’s palsy has been estimated to occur in the United States every 10 minutes.⁸ Guillain-Barré syndrome and Lyme disease are also in this category, as is Ramsey-Hunt syndrome. Patients with Lyme disease may have a history of a tick bite or rash.¹⁴

Trauma can also cause acute facial nerve paralysis (eg, blunt trauma-associated facial fracture, penetrating trauma, birth trauma). Unilateral central facial weakness can have a neurological cause, such as a lesion to the contralateral cortex, subcortical white matter, or internal capsule.^2,15 Otitis media can sometimes cause facial paralysis.¹⁶ A cholesteatoma can cause acute facial paralysis.² Malignancies cause 5% of all cases of facial paralysis. Primary parotid tumors of various types are in this category. Metastatic disease from breast, lung, skin, colon, and kidney may cause facial paralysis. As our case illustrates, CPA tumors can cause facial paralysis.¹⁵ It is important to also note that a patient can have both a Bell’s palsy and a concurrent disease. There are a number of case reports in the literature that describe acute onset of facial paralysis as a presenting symptom of malignancy.¹⁷ In addition, there are cases wherein a neurological finding on imaging, such as an acoustic neuroma, was presumed to be the cause of facial paralysis, yet the patient’s symptoms resolved in a manner consistent with Bell’s palsy.¹⁸

For example, Lagman et al¹⁹ described a patient in which a CPA lipoma was presumed to be the cause of the facial paralysis, but the eventual outcome showed the lipoma to have been an incidentaloma.

Conclusion

This case demonstrates a presenting symptom of facial palsy and the presence of a CPA tumor. The presence of vertigo along with other historical and physical examination findings inconsistent with Bell’s palsy prompted the CT scan of the head. A review of the literature suggests a number of important findings in patients with facial palsy to assist the clinician in distinguishing true Bell’s palsy from other diseases that can mimic this condition. This case serves as a reminder of the need to perform a thorough and diligent workup to determine the presence or absence of other neurologic findings prior to closing on the diagnosis of Bell’s palsy.

Facial paralysis is a common medical complaint—one that has fascinated ancient and contemporary physicians alike.¹ An idiopathic facial nerve paresis involving the lower motor neuron was described in 1821 by Sir Charles Bell. This entity became known as a Bell’s palsy, the hallmark of which was weakness or complete paralysis of the muscles of one side of the face, with no sparing of the muscles of the forehead. However, not all facial paralysis is due to Bell’s palsy.

We present a case of a patient with a Bell’s palsy mimic to facilitate and guide the differential diagnosis and distinguish conditions from the classical presentation that Bell first described to the more concerning symptoms that may not be immediately obvious. Our case further underscores the importance of performing a thorough assessment to determine the presence of other neurological findings.

Case

A 61-year-old woman presented to the ED for evaluation of right facial droop and sensation of “room spinning.” The patient stated both symptoms began approximately 36 hours prior to presentation, upon awakening. She further noted that the right side of her face felt “funny” and numb.

The patient denied any headache, neck or chest pain, extremity numbness, or weakness, but stated that she felt like she was going to fall toward her right side whenever she attempted to walk. The patient’s medical history was significant for hypertension, for which she was taking losartan. Her surgical history was notable for a left oophorectomy secondary to an ovarian cyst. Regarding the social history, the patient admitted to smoking 90 packs of cigarettes per year, but denied alcohol or illicit drug use.

Upon arrival at the ED, the patient’s vital signs were: blood pressure, 164/86 mm Hg: pulse, 89 beats/min; respiratory rate, 18 breaths/min; and temperature, 98.6°F. Oxygen saturation was 98% on room air.

Physical examination revealed the patient had a right facial droop consistent with right facial palsy. She was unable to wrinkle her right forehead or fully close her right eye. There were no field cuts on confrontation. The patient’s speech was noticeable for a mild dysarthria. The motor examination revealed mild weakness of the left upper extremity and impaired right facial sensation. There were no rashes noted on the face, head, or ears. The patient had slightly impaired hearing in the right ear, which was new in onset. The remainder of the physical examination was unremarkable.

Although the patient exhibited the classic signs of Bell’s palsy, including complete paralysis of the muscles of one side of the face, inability to wrinkle the muscle of the right forehead, and inability to fully close the right eye, she also had concerning symptoms of vertigo, dysarthria, and contralateral upper extremity weakness.

A computed tomography (CT) scan of the head was ordered, which revealed a large mass lesion centered in the right petrous apex, with an associated large component extending medially into the right cerebellopontine angle (CPA) that caused a mass effect on the adjacent brainstem (Figures 1a and 1b).

Discussion

Accounts of facial paralysis and facial nerve disorders have been noted throughout history and include accounts of the condition by Hippocrates.¹ Bell’s palsy was named after surgeon Sir Charles Bell, who described a peripheral-nerve paralysis of the facial nerve in 1821. Bell’s work helped to elucidate the anatomy and functional role of the facial nerve.^1,2

Signs and Symptoms

The classic presentation of Bell’s palsy is weakness or complete paralysis of the muscles of one side of the face, with no sparing of the muscles of the forehead. The eyelid on the affected side generally does not close, which can result in ocular irritation due to ineffective lubrication.

A scoring system has been developed by House and Brackmann which grades the degree impairment based on such characteristics as facial muscle function and eye closure.^3,4 Approximately 96% of patients with a Bell’s palsy will improve to a House-Brackmann score of 2 or better within 1 year from diagnosis,⁵ and 85% of patients with Bell’s palsy will show at least some improvement within 3 weeks of onset (Table).² Although the classic description of Bell’s palsy notes the condition as idiopathic, there is an increasing body of evidence in the literature showing a link to herpes simplex virus 1.^5-7

Ramsey-Hunt Syndrome

The relationship between Bell’s palsy and Ramsey-Hunt syndrome is complex and controversial. Ramsey-Hunt syndrome is a constellation of possible complications from varicella-virus infection. Symptoms of Ramsey-Hunt syndrome include facial paralysis, tinnitus, hearing loss, vertigo, hyperacusis (increased sensitivity to certain frequencies and volume ranges of sound), and decreased ocular tearing.⁸ Due to the nature of symptoms associated with Ramsey-Hunt syndrome, it is apparent that the condition involves more than the seventh cranial nerve. In fact, studies have shown that Ramsey-Hunt syndrome can affect the fifth, sixth, eighth, and ninth cranial nerves.⁸

Ramsey-Hunt syndrome, which can present in the absence of cutaneous rash (referred to as zoster sine herpete), is estimated to occur in 8% to 20% of unilateral facial nerve palsies in adult patients.^8,9 Regardless of the etiology of Bell’s palsy, a review of the literature makes it clear that facial nerve paralysis is not synonymous with Bell’s palsy.¹⁰ In one example, Yetter et al¹⁰ describe the case of a patient who, though initially diagnosed with Bell’s palsy, ultimately was found to have a facial palsy due to a parotid gland malignancy.

Likewise, Stomeo¹¹ describes a case of a patient with facial paralysis and profound ipsilateral hearing loss who ultimately was found to have a mucoepithelial carcinoma of the parotid gland. In their report, the authors note that approximately 80% of facial nerve paralysis is due to Bell’s palsy, while 5% is due to malignancy.

In another report, Clemis¹² describes a case in which a patient who initially was diagnosed with Bell’s palsy eventually was found to have an adenoid cystic carcinoma of the parotid. Thus, the authors appropriately emphasize in their report that “all that palsies is not Bell’s.”

Differential Diagnosis

Historical factors, including timing and duration of symptom onset, help to distinguish a Bell’s palsy from other disorders that can mimic this condition. In their study, Brach VanSwewaringen¹³ highlight the fact that “not all facial paralysis is Bell’s palsy.” In their review, the authors describe clues to help distinguish conditions that mimic Bell’s palsy. For example, maximal weakness from Bell’s Palsy typically occurs within 3 to 7 days from symptom onset, and that a more gradual onset of symptoms, with slow or negligible improvement over 6 to 12 months, is more indicative of a space-occupying lesion than Bell’s palsy.¹³It is, however, important to note that although the patient in our case had a central lesion, she experienced an acute onset of symptoms.

The presence of additional symptoms may also suggest an alternative diagnosis. Brach and VanSwearingen¹³ further noted that symptoms associated with the eighth nerve, such as vertigo, tinnitus, and hearing loss may be found in patients with a CPA tumor. In patients with larger tumors, ninth and 10th nerve symptoms, including the impaired hearing noted in our patient, may be present. Some patients with ninth and 10th nerve symptoms may perceive a sense of facial numbness, but actual sensory changes in the facial nerve distribution are unlikely in Bell’s palsy. Gustatory changes, however, are consistent with Bell’s palsy.

Ear pain is consistent with Bell’s palsy and is a signal to be vigilant for the possible emergence of an ear rash, which would suggest the diagnosis of herpes zoster oticus along the trajectory of Ramsey-Hunt syndrome. Facial pain in the area of the facial nerve is inconsistent with Bell’s palsy, while hyperacusis is consistent with Bell’s palsy. Hearing loss is an eighth nerve symptom that is inconsistent with Bell’s palsy.

Similarly, there are physical examination findings that can help distinguish a true Bell’s palsy from a mimic. Changes in tear production are consistent with Bell’s palsy, but imbalance and disequilibrium are not.¹⁴

As previously noted, the patient in this case had difficulty walking and felt as if she was falling toward her right side.

One way to organize the causes of facial paralysis has been proposed by Adour et al.¹⁵ In this system, etiologies are listed as either acute paralysis or chronic, progressive paralysis. Acute paralysis (ie, the sudden onset of symptoms with maximal severity within 2 weeks), of which Bell’s palsy is the most common, can be seen in cases of polyneuritis.

A new case of Bell’s palsy has been estimated to occur in the United States every 10 minutes.⁸ Guillain-Barré syndrome and Lyme disease are also in this category, as is Ramsey-Hunt syndrome. Patients with Lyme disease may have a history of a tick bite or rash.¹⁴

Trauma can also cause acute facial nerve paralysis (eg, blunt trauma-associated facial fracture, penetrating trauma, birth trauma). Unilateral central facial weakness can have a neurological cause, such as a lesion to the contralateral cortex, subcortical white matter, or internal capsule.^2,15 Otitis media can sometimes cause facial paralysis.¹⁶ A cholesteatoma can cause acute facial paralysis.² Malignancies cause 5% of all cases of facial paralysis. Primary parotid tumors of various types are in this category. Metastatic disease from breast, lung, skin, colon, and kidney may cause facial paralysis. As our case illustrates, CPA tumors can cause facial paralysis.¹⁵ It is important to also note that a patient can have both a Bell’s palsy and a concurrent disease. There are a number of case reports in the literature that describe acute onset of facial paralysis as a presenting symptom of malignancy.¹⁷ In addition, there are cases wherein a neurological finding on imaging, such as an acoustic neuroma, was presumed to be the cause of facial paralysis, yet the patient’s symptoms resolved in a manner consistent with Bell’s palsy.¹⁸

For example, Lagman et al¹⁹ described a patient in which a CPA lipoma was presumed to be the cause of the facial paralysis, but the eventual outcome showed the lipoma to have been an incidentaloma.

Conclusion

This case demonstrates a presenting symptom of facial palsy and the presence of a CPA tumor. The presence of vertigo along with other historical and physical examination findings inconsistent with Bell’s palsy prompted the CT scan of the head. A review of the literature suggests a number of important findings in patients with facial palsy to assist the clinician in distinguishing true Bell’s palsy from other diseases that can mimic this condition. This case serves as a reminder of the need to perform a thorough and diligent workup to determine the presence or absence of other neurologic findings prior to closing on the diagnosis of Bell’s palsy.

With advances in the understanding of cellular pathways, molecular genetics, and immunology, new drugs for cancer are being released at an increasing rate. A variety of novel agents have recently become available for use, generating excitement for patients and oncologists. Keeping track of all of these new agents is increasingly challenging. This brief review will summarize some of the newest drugs, their indications, and benefits (see related article).

Therapies by tumor

Breast cancer

CDK4/6 inhibitors. The CDK4/6 inhibitor palbociclib was approved in 2015 for the treatment of estrogen-positive, HER2-negative advanced breast cancer, and this year, two more drugs in this class – ribociclib and abemaciclib – were approved for the treatment of hormone receptor–positive breast cancer.

Ribociclib (Kisqali) 600 mg daily (3 weeks on, 1 week off) is approved for use in combination with an aromatase inhibitor. In the study on which the approval was based, there was a response rate of 53% for patients in the study group, compared with 37% for those who received aromatase inhibitor alone (progression-free survival (PFS), not reached vs 14.7 months for single-agent aromatase inhibitor).¹ The occurrence of neutropenia seemed to be similar to that in patients receiving palbociclib. However, unlike with palbociclib, ribociclib requires ECG monitoring for QTc prolongation as well as monitoring of liver function tests.

Abemaciclib (Verzenio) has been approved in combination with fulvestrant as well as a monotherapy.² PFS was 16.4 months for abemaciclib (150 mg bid in combination with fulvestrant), compared with 9.3 months for fulvestrant alone, with corresponding response rates of 48% and 21%. As monotherapy, abemaciclib 200 mg bid had a response rate of 20% with a duration of response of 8.6 months.

Tyrosine kinase inhibitors. The tyrosine kinase inhibitor neratinib (Nerlynx) was approved for extended adjuvant treatment of HER2-positive breast cancer after 1 year of adjuvant trastuzumab.³ Given at 240 mg (6 tablets) daily for a year, compared with a no-treatment control arm, it demonstrated an improvement in invasive disease-free survival (DFS) at 2 years from 91.9% to 94.2%, with no difference in overall survival yet noted. It is associated with diarrhea and also requires hepatic function monitoring.
 

Acute myelogenous leukemia

Multiple new agents were recently approved for use in acute myelogenous leukemia (AML), after decades of slow advance in new drug development.

Midostaurin (Rydapt) is an FLT3 inhibitor approved for use in combination with daunorubicin and Ara-C (cytosine arabinoside) for newly diagnosed AML with FLT3 mutations, which occur in about 30% of AML patients.⁴ It is given orally on days 8-21 at 50 mg bid with induction and consolidation.

In the study on which the approval was based, there was a 10% improvement in overall survival for this subset of AML patients who have a typically a worse prognosis. Event-free survival in patients in the study group was 8.2 months, compared with 3 months in the control arm patients, who did not receive the agent. The drug was also approved for aggressive systemic mastocytosis.

Enasidenib (Idhifa) has been approved for AML with an IDH2 mutation in the refractory/relapsed settings.⁵IDH2 mutations are present in about 20% of patients with AML. Given orally at 100 mg daily as a single agent, enasidenib was associated with a 19% complete remission rate. Patients need to be monitored for differentiation syndrome, somewhat similar to what is seen with ATRA with acute promyelocytic leukemia.

Liposomal daunorubicin and cytarabine (Vyxeos) was approved for newly diagnosed therapy- or myelodysplasia-related AML.⁶ This novel liposomal formulation combines two standard agents and is given intravenously on days 1, 3 and 5 over 90 minutes as daunorubicin 44 mg/m² and cytarabine 100 mg/ m². (For a second induction and in lower dose on consolidation cycles, it is given only on days 1 and 3). The liposomal formulation achieved a superior complete response rate compared with the standard 7+3 daunorubicin plus cytarabine regimen (38% vs 26%, respectively) and longer overall survival (9.6 versus 5.9 months) in these generally poor prognosis subsets.

Gemtuzumab ozogamicin (Mylotarg) was initially approved in 2000 but withdrawn from use in 2010 after trials failed to confirm benefit and demonstrated safety concerns. It has now been re-released in a lower dose and schedule from its original label.⁷ This immunoconjugate of an anti-CD33 bound to calicheamicin is approved for CD33-positive AML. Given at 3 mg/m² on days 1, 4, and 7 in combination with standard daunorubicin–cytarabine induction chemotherapy, it improved event-free survival from 9.5 to 17.3 months. When administered as a single agent (6 mg/m² on day 1 and 3 mg/m² on day 8) in patients who were unable or unwilling to tolerate standard chemotherapy, it improved overall survival (4.9 months versus 3.6 months for best supportive care). As a single agent in relapsed AML, given at 3 mg/m² days 1, 4, and 7 and followed by cytarabine consolidation, it was associated with a 26% complete response rate, with a median relapse-free survival of 11.6 months.
 

Ovarian/fallopian tube cancers

PARP inhibitors. For patients with ovarian/fallopian tube cancer, there are new indications and agents for PARP inhibition, including for patients with BRCA mutations (both somatic and germline) and those without BRCA mutations.

Olaparib (Lynparza) was previously approved only in a fourth-line setting for germline BRCA-mutated patients with advanced ovarian cancer, with a response rate of 34% with a median duration of 7.9 months. Given at 300 mg orally bid, it is now approved for use in maintenance in recurrence after response to platinum-based chemotherapy after 2 or more lines of therapy regardless of BRCA status. In this setting, progression-free survival increased to 8.4 months, compared with 4.8 months for placebo.⁸

Rubicarib (Rubraca) is approved for BRCA-mutated patients (either germline or somatic) with advanced ovarian cancer after two or more lines of chemotherapy.⁹ At 600 mg orally bid, results from phase 2 trials noted a 54% response rate, with a median duration of 9.2 months.

Niraparib (Zejula) is approved for use in maintenance in recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancers after platinum-based chemotherapy.¹⁰ In patients with germline BRCA mutations, niraparib at 300 mg orally daily resulted in a PFS of 21 months, compared with 5.5 months with placebo; PFS in patients with nongermline BRCA mutations was 9.3 versus 3.9 months, respectively.
 

Non-small cell lung cancer with EML-4 alk translocation

Crizotinib (Xalkori) has been the mainstay for treatment of for EML4-alk translocated non-small cell lung cancer. However, alectinib (Alcensa), previously for predominantly second-line use, seems more active than crizotinib in the first-line setting, particularly in the treatment and prevention of CNS metastases.

In addition, brigantinib (Alunbrig) has been approved for patients who are intolerant/refractory to crizotinib.¹¹ At 90 mg once daily for 7 days, then escalating to 180 mg daily, it was noted to have a 50% response rate in crizotinib failures, including in the CNS.
 

Ceritinib (Zykadia) was approved at 750 mg once daily for EML4 alk positive NSCLC.¹² In first line it had a response rate of 73% (versus 27% for chemotherapy) with a remission duration of 23.9 months (versus 11.1 months for chemotherapy).
 

Therapies by drug class

PD-1/PD-L1 antibodies

Anti-PD-1 antibodies nivolumab (Opdivo) and pembrolizumab (Keytruda) are widely used for a range of tumor types. Newer approvals for pembrolizumab are for adenocarcinoma of the stomach/gastro-esophageal junction with at least 1% PD-L1 expression, and in any tumor demonstrated to be MSI-high. Newer indications for nivolumab are for bladder cancer, MSI-high colon cancer, and for hepatoma previously treated with sorafenib. The anti-PD-L1 antibody atezolizumab (Tencentriq) is now approved for platinum-resistant metastatic lung cancer, in addition to platinum-ineligible and platinum-resistant urothelial cancer.

Avelumab (Bavencio) is an anti-PD-L1 approved for both Merkel cell and previously treated urothelial cancers at a dose of 10 mg/kg every 2 weeks.¹³ It demonstrated a 33% response rate for Merkel cell and a 16% response rate for urothelial cancer.

Durvalumab (Imfinzi) is another anti PD-L1 antibody approved at 10 mg/kg every 2 weeks for previously treated urothelial cancer with a 17% response rate (RR: PD-L1 high, 26%; low, 4%).¹⁴

PI3K kinase inhibitors

Copanlisib (Aliqopa) is a PI3K inhibitor approved for relapsed follicular lymphoma in patients who have progressed after two previous lines of therapy.¹⁵ It is a 60-mg, 1-hour infusion given on days 1, 8, and 15 every 28 days. In a phase 2 trial, it had a 59% response rate (14% complete response) and a median response duration of 12.2 months.

BTK inhibitors

Acalabruitnib (Calquence) is approved for adults with previously treated mantle cell lymphoma. In a phase 2 trial at 100 mg orally bid, it achieved an 80% overall and 40% complete response rate.¹⁶ These response rates are higher than were seen for ibrutinib in its original phase 2 trial. The spectrum of toxicities seems similar to ibruitinib and includes bleeding, cytopenias, infection, and atrial fibrillation.

CD19 CAR-T cells

Perhaps the most exciting and novel new agents are genetically engineered autologous T cells. Tisagenlecleucel (Kymriah), a chimeric antigen receptor T cell (CART) that targets CD19 is approved for refractory B cell precursor acute lymphoblastic leukemia (in patients under 25 years) where the complete response rate was 83% (including patients with incomplete blood count recovery).¹⁷



Axicabtagene ciloleucel (aci-cel; Yescarta), also CD19-directed CART, is approved for adults with relapsed or refractory non-Hodgkin lymphoma after two lines of previous therapy (specifically large-cell lymphoma, primary mediastinal large B-cell lymphoma, and transformed follicular lymphoma). Response rate was 72% (complete, 51%; partial, 21%), with a median duration of response of 9.2 months.¹⁸

With advances in the understanding of cellular pathways, molecular genetics, and immunology, new drugs for cancer are being released at an increasing rate. A variety of novel agents have recently become available for use, generating excitement for patients and oncologists. Keeping track of all of these new agents is increasingly challenging. This brief review will summarize some of the newest drugs, their indications, and benefits (see related article).

Therapies by tumor

Breast cancer

CDK4/6 inhibitors. The CDK4/6 inhibitor palbociclib was approved in 2015 for the treatment of estrogen-positive, HER2-negative advanced breast cancer, and this year, two more drugs in this class – ribociclib and abemaciclib – were approved for the treatment of hormone receptor–positive breast cancer.

Ribociclib (Kisqali) 600 mg daily (3 weeks on, 1 week off) is approved for use in combination with an aromatase inhibitor. In the study on which the approval was based, there was a response rate of 53% for patients in the study group, compared with 37% for those who received aromatase inhibitor alone (progression-free survival (PFS), not reached vs 14.7 months for single-agent aromatase inhibitor).¹ The occurrence of neutropenia seemed to be similar to that in patients receiving palbociclib. However, unlike with palbociclib, ribociclib requires ECG monitoring for QTc prolongation as well as monitoring of liver function tests.

Abemaciclib (Verzenio) has been approved in combination with fulvestrant as well as a monotherapy.² PFS was 16.4 months for abemaciclib (150 mg bid in combination with fulvestrant), compared with 9.3 months for fulvestrant alone, with corresponding response rates of 48% and 21%. As monotherapy, abemaciclib 200 mg bid had a response rate of 20% with a duration of response of 8.6 months.

Tyrosine kinase inhibitors. The tyrosine kinase inhibitor neratinib (Nerlynx) was approved for extended adjuvant treatment of HER2-positive breast cancer after 1 year of adjuvant trastuzumab.³ Given at 240 mg (6 tablets) daily for a year, compared with a no-treatment control arm, it demonstrated an improvement in invasive disease-free survival (DFS) at 2 years from 91.9% to 94.2%, with no difference in overall survival yet noted. It is associated with diarrhea and also requires hepatic function monitoring.
 

Acute myelogenous leukemia

Multiple new agents were recently approved for use in acute myelogenous leukemia (AML), after decades of slow advance in new drug development.

Midostaurin (Rydapt) is an FLT3 inhibitor approved for use in combination with daunorubicin and Ara-C (cytosine arabinoside) for newly diagnosed AML with FLT3 mutations, which occur in about 30% of AML patients.⁴ It is given orally on days 8-21 at 50 mg bid with induction and consolidation.

In the study on which the approval was based, there was a 10% improvement in overall survival for this subset of AML patients who have a typically a worse prognosis. Event-free survival in patients in the study group was 8.2 months, compared with 3 months in the control arm patients, who did not receive the agent. The drug was also approved for aggressive systemic mastocytosis.

Enasidenib (Idhifa) has been approved for AML with an IDH2 mutation in the refractory/relapsed settings.⁵IDH2 mutations are present in about 20% of patients with AML. Given orally at 100 mg daily as a single agent, enasidenib was associated with a 19% complete remission rate. Patients need to be monitored for differentiation syndrome, somewhat similar to what is seen with ATRA with acute promyelocytic leukemia.

Liposomal daunorubicin and cytarabine (Vyxeos) was approved for newly diagnosed therapy- or myelodysplasia-related AML.⁶ This novel liposomal formulation combines two standard agents and is given intravenously on days 1, 3 and 5 over 90 minutes as daunorubicin 44 mg/m² and cytarabine 100 mg/ m². (For a second induction and in lower dose on consolidation cycles, it is given only on days 1 and 3). The liposomal formulation achieved a superior complete response rate compared with the standard 7+3 daunorubicin plus cytarabine regimen (38% vs 26%, respectively) and longer overall survival (9.6 versus 5.9 months) in these generally poor prognosis subsets.

Gemtuzumab ozogamicin (Mylotarg) was initially approved in 2000 but withdrawn from use in 2010 after trials failed to confirm benefit and demonstrated safety concerns. It has now been re-released in a lower dose and schedule from its original label.⁷ This immunoconjugate of an anti-CD33 bound to calicheamicin is approved for CD33-positive AML. Given at 3 mg/m² on days 1, 4, and 7 in combination with standard daunorubicin–cytarabine induction chemotherapy, it improved event-free survival from 9.5 to 17.3 months. When administered as a single agent (6 mg/m² on day 1 and 3 mg/m² on day 8) in patients who were unable or unwilling to tolerate standard chemotherapy, it improved overall survival (4.9 months versus 3.6 months for best supportive care). As a single agent in relapsed AML, given at 3 mg/m² days 1, 4, and 7 and followed by cytarabine consolidation, it was associated with a 26% complete response rate, with a median relapse-free survival of 11.6 months.
 

Ovarian/fallopian tube cancers

PARP inhibitors. For patients with ovarian/fallopian tube cancer, there are new indications and agents for PARP inhibition, including for patients with BRCA mutations (both somatic and germline) and those without BRCA mutations.

Olaparib (Lynparza) was previously approved only in a fourth-line setting for germline BRCA-mutated patients with advanced ovarian cancer, with a response rate of 34% with a median duration of 7.9 months. Given at 300 mg orally bid, it is now approved for use in maintenance in recurrence after response to platinum-based chemotherapy after 2 or more lines of therapy regardless of BRCA status. In this setting, progression-free survival increased to 8.4 months, compared with 4.8 months for placebo.⁸

Rubicarib (Rubraca) is approved for BRCA-mutated patients (either germline or somatic) with advanced ovarian cancer after two or more lines of chemotherapy.⁹ At 600 mg orally bid, results from phase 2 trials noted a 54% response rate, with a median duration of 9.2 months.

Niraparib (Zejula) is approved for use in maintenance in recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancers after platinum-based chemotherapy.¹⁰ In patients with germline BRCA mutations, niraparib at 300 mg orally daily resulted in a PFS of 21 months, compared with 5.5 months with placebo; PFS in patients with nongermline BRCA mutations was 9.3 versus 3.9 months, respectively.
 

Non-small cell lung cancer with EML-4 alk translocation

Crizotinib (Xalkori) has been the mainstay for treatment of for EML4-alk translocated non-small cell lung cancer. However, alectinib (Alcensa), previously for predominantly second-line use, seems more active than crizotinib in the first-line setting, particularly in the treatment and prevention of CNS metastases.

In addition, brigantinib (Alunbrig) has been approved for patients who are intolerant/refractory to crizotinib.¹¹ At 90 mg once daily for 7 days, then escalating to 180 mg daily, it was noted to have a 50% response rate in crizotinib failures, including in the CNS.
 

Ceritinib (Zykadia) was approved at 750 mg once daily for EML4 alk positive NSCLC.¹² In first line it had a response rate of 73% (versus 27% for chemotherapy) with a remission duration of 23.9 months (versus 11.1 months for chemotherapy).
 

Therapies by drug class

PD-1/PD-L1 antibodies

Anti-PD-1 antibodies nivolumab (Opdivo) and pembrolizumab (Keytruda) are widely used for a range of tumor types. Newer approvals for pembrolizumab are for adenocarcinoma of the stomach/gastro-esophageal junction with at least 1% PD-L1 expression, and in any tumor demonstrated to be MSI-high. Newer indications for nivolumab are for bladder cancer, MSI-high colon cancer, and for hepatoma previously treated with sorafenib. The anti-PD-L1 antibody atezolizumab (Tencentriq) is now approved for platinum-resistant metastatic lung cancer, in addition to platinum-ineligible and platinum-resistant urothelial cancer.

Avelumab (Bavencio) is an anti-PD-L1 approved for both Merkel cell and previously treated urothelial cancers at a dose of 10 mg/kg every 2 weeks.¹³ It demonstrated a 33% response rate for Merkel cell and a 16% response rate for urothelial cancer.

Durvalumab (Imfinzi) is another anti PD-L1 antibody approved at 10 mg/kg every 2 weeks for previously treated urothelial cancer with a 17% response rate (RR: PD-L1 high, 26%; low, 4%).¹⁴

PI3K kinase inhibitors

Copanlisib (Aliqopa) is a PI3K inhibitor approved for relapsed follicular lymphoma in patients who have progressed after two previous lines of therapy.¹⁵ It is a 60-mg, 1-hour infusion given on days 1, 8, and 15 every 28 days. In a phase 2 trial, it had a 59% response rate (14% complete response) and a median response duration of 12.2 months.

BTK inhibitors

Acalabruitnib (Calquence) is approved for adults with previously treated mantle cell lymphoma. In a phase 2 trial at 100 mg orally bid, it achieved an 80% overall and 40% complete response rate.¹⁶ These response rates are higher than were seen for ibrutinib in its original phase 2 trial. The spectrum of toxicities seems similar to ibruitinib and includes bleeding, cytopenias, infection, and atrial fibrillation.

CD19 CAR-T cells

Perhaps the most exciting and novel new agents are genetically engineered autologous T cells. Tisagenlecleucel (Kymriah), a chimeric antigen receptor T cell (CART) that targets CD19 is approved for refractory B cell precursor acute lymphoblastic leukemia (in patients under 25 years) where the complete response rate was 83% (including patients with incomplete blood count recovery).¹⁷



Axicabtagene ciloleucel (aci-cel; Yescarta), also CD19-directed CART, is approved for adults with relapsed or refractory non-Hodgkin lymphoma after two lines of previous therapy (specifically large-cell lymphoma, primary mediastinal large B-cell lymphoma, and transformed follicular lymphoma). Response rate was 72% (complete, 51%; partial, 21%), with a median duration of response of 9.2 months.¹⁸

With advances in the understanding of cellular pathways, molecular genetics, and immunology, new drugs for cancer are being released at an increasing rate. A variety of novel agents have recently become available for use, generating excitement for patients and oncologists. Keeping track of all of these new agents is increasingly challenging. This brief review will summarize some of the newest drugs, their indications, and benefits (see related article).

Therapies by tumor

Breast cancer

CDK4/6 inhibitors. The CDK4/6 inhibitor palbociclib was approved in 2015 for the treatment of estrogen-positive, HER2-negative advanced breast cancer, and this year, two more drugs in this class – ribociclib and abemaciclib – were approved for the treatment of hormone receptor–positive breast cancer.

Ribociclib (Kisqali) 600 mg daily (3 weeks on, 1 week off) is approved for use in combination with an aromatase inhibitor. In the study on which the approval was based, there was a response rate of 53% for patients in the study group, compared with 37% for those who received aromatase inhibitor alone (progression-free survival (PFS), not reached vs 14.7 months for single-agent aromatase inhibitor).¹ The occurrence of neutropenia seemed to be similar to that in patients receiving palbociclib. However, unlike with palbociclib, ribociclib requires ECG monitoring for QTc prolongation as well as monitoring of liver function tests.

Abemaciclib (Verzenio) has been approved in combination with fulvestrant as well as a monotherapy.² PFS was 16.4 months for abemaciclib (150 mg bid in combination with fulvestrant), compared with 9.3 months for fulvestrant alone, with corresponding response rates of 48% and 21%. As monotherapy, abemaciclib 200 mg bid had a response rate of 20% with a duration of response of 8.6 months.

Tyrosine kinase inhibitors. The tyrosine kinase inhibitor neratinib (Nerlynx) was approved for extended adjuvant treatment of HER2-positive breast cancer after 1 year of adjuvant trastuzumab.³ Given at 240 mg (6 tablets) daily for a year, compared with a no-treatment control arm, it demonstrated an improvement in invasive disease-free survival (DFS) at 2 years from 91.9% to 94.2%, with no difference in overall survival yet noted. It is associated with diarrhea and also requires hepatic function monitoring.
 

Acute myelogenous leukemia

Multiple new agents were recently approved for use in acute myelogenous leukemia (AML), after decades of slow advance in new drug development.

Midostaurin (Rydapt) is an FLT3 inhibitor approved for use in combination with daunorubicin and Ara-C (cytosine arabinoside) for newly diagnosed AML with FLT3 mutations, which occur in about 30% of AML patients.⁴ It is given orally on days 8-21 at 50 mg bid with induction and consolidation.

In the study on which the approval was based, there was a 10% improvement in overall survival for this subset of AML patients who have a typically a worse prognosis. Event-free survival in patients in the study group was 8.2 months, compared with 3 months in the control arm patients, who did not receive the agent. The drug was also approved for aggressive systemic mastocytosis.

Enasidenib (Idhifa) has been approved for AML with an IDH2 mutation in the refractory/relapsed settings.⁵IDH2 mutations are present in about 20% of patients with AML. Given orally at 100 mg daily as a single agent, enasidenib was associated with a 19% complete remission rate. Patients need to be monitored for differentiation syndrome, somewhat similar to what is seen with ATRA with acute promyelocytic leukemia.

Liposomal daunorubicin and cytarabine (Vyxeos) was approved for newly diagnosed therapy- or myelodysplasia-related AML.⁶ This novel liposomal formulation combines two standard agents and is given intravenously on days 1, 3 and 5 over 90 minutes as daunorubicin 44 mg/m² and cytarabine 100 mg/ m². (For a second induction and in lower dose on consolidation cycles, it is given only on days 1 and 3). The liposomal formulation achieved a superior complete response rate compared with the standard 7+3 daunorubicin plus cytarabine regimen (38% vs 26%, respectively) and longer overall survival (9.6 versus 5.9 months) in these generally poor prognosis subsets.

Gemtuzumab ozogamicin (Mylotarg) was initially approved in 2000 but withdrawn from use in 2010 after trials failed to confirm benefit and demonstrated safety concerns. It has now been re-released in a lower dose and schedule from its original label.⁷ This immunoconjugate of an anti-CD33 bound to calicheamicin is approved for CD33-positive AML. Given at 3 mg/m² on days 1, 4, and 7 in combination with standard daunorubicin–cytarabine induction chemotherapy, it improved event-free survival from 9.5 to 17.3 months. When administered as a single agent (6 mg/m² on day 1 and 3 mg/m² on day 8) in patients who were unable or unwilling to tolerate standard chemotherapy, it improved overall survival (4.9 months versus 3.6 months for best supportive care). As a single agent in relapsed AML, given at 3 mg/m² days 1, 4, and 7 and followed by cytarabine consolidation, it was associated with a 26% complete response rate, with a median relapse-free survival of 11.6 months.
 

Ovarian/fallopian tube cancers

PARP inhibitors. For patients with ovarian/fallopian tube cancer, there are new indications and agents for PARP inhibition, including for patients with BRCA mutations (both somatic and germline) and those without BRCA mutations.

Olaparib (Lynparza) was previously approved only in a fourth-line setting for germline BRCA-mutated patients with advanced ovarian cancer, with a response rate of 34% with a median duration of 7.9 months. Given at 300 mg orally bid, it is now approved for use in maintenance in recurrence after response to platinum-based chemotherapy after 2 or more lines of therapy regardless of BRCA status. In this setting, progression-free survival increased to 8.4 months, compared with 4.8 months for placebo.⁸

Rubicarib (Rubraca) is approved for BRCA-mutated patients (either germline or somatic) with advanced ovarian cancer after two or more lines of chemotherapy.⁹ At 600 mg orally bid, results from phase 2 trials noted a 54% response rate, with a median duration of 9.2 months.

Niraparib (Zejula) is approved for use in maintenance in recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancers after platinum-based chemotherapy.¹⁰ In patients with germline BRCA mutations, niraparib at 300 mg orally daily resulted in a PFS of 21 months, compared with 5.5 months with placebo; PFS in patients with nongermline BRCA mutations was 9.3 versus 3.9 months, respectively.
 

Non-small cell lung cancer with EML-4 alk translocation

Crizotinib (Xalkori) has been the mainstay for treatment of for EML4-alk translocated non-small cell lung cancer. However, alectinib (Alcensa), previously for predominantly second-line use, seems more active than crizotinib in the first-line setting, particularly in the treatment and prevention of CNS metastases.

In addition, brigantinib (Alunbrig) has been approved for patients who are intolerant/refractory to crizotinib.¹¹ At 90 mg once daily for 7 days, then escalating to 180 mg daily, it was noted to have a 50% response rate in crizotinib failures, including in the CNS.
 

Ceritinib (Zykadia) was approved at 750 mg once daily for EML4 alk positive NSCLC.¹² In first line it had a response rate of 73% (versus 27% for chemotherapy) with a remission duration of 23.9 months (versus 11.1 months for chemotherapy).
 

Therapies by drug class

PD-1/PD-L1 antibodies

Anti-PD-1 antibodies nivolumab (Opdivo) and pembrolizumab (Keytruda) are widely used for a range of tumor types. Newer approvals for pembrolizumab are for adenocarcinoma of the stomach/gastro-esophageal junction with at least 1% PD-L1 expression, and in any tumor demonstrated to be MSI-high. Newer indications for nivolumab are for bladder cancer, MSI-high colon cancer, and for hepatoma previously treated with sorafenib. The anti-PD-L1 antibody atezolizumab (Tencentriq) is now approved for platinum-resistant metastatic lung cancer, in addition to platinum-ineligible and platinum-resistant urothelial cancer.

Avelumab (Bavencio) is an anti-PD-L1 approved for both Merkel cell and previously treated urothelial cancers at a dose of 10 mg/kg every 2 weeks.¹³ It demonstrated a 33% response rate for Merkel cell and a 16% response rate for urothelial cancer.

Durvalumab (Imfinzi) is another anti PD-L1 antibody approved at 10 mg/kg every 2 weeks for previously treated urothelial cancer with a 17% response rate (RR: PD-L1 high, 26%; low, 4%).¹⁴

PI3K kinase inhibitors

Copanlisib (Aliqopa) is a PI3K inhibitor approved for relapsed follicular lymphoma in patients who have progressed after two previous lines of therapy.¹⁵ It is a 60-mg, 1-hour infusion given on days 1, 8, and 15 every 28 days. In a phase 2 trial, it had a 59% response rate (14% complete response) and a median response duration of 12.2 months.

BTK inhibitors

Acalabruitnib (Calquence) is approved for adults with previously treated mantle cell lymphoma. In a phase 2 trial at 100 mg orally bid, it achieved an 80% overall and 40% complete response rate.¹⁶ These response rates are higher than were seen for ibrutinib in its original phase 2 trial. The spectrum of toxicities seems similar to ibruitinib and includes bleeding, cytopenias, infection, and atrial fibrillation.

CD19 CAR-T cells

Perhaps the most exciting and novel new agents are genetically engineered autologous T cells. Tisagenlecleucel (Kymriah), a chimeric antigen receptor T cell (CART) that targets CD19 is approved for refractory B cell precursor acute lymphoblastic leukemia (in patients under 25 years) where the complete response rate was 83% (including patients with incomplete blood count recovery).¹⁷



Axicabtagene ciloleucel (aci-cel; Yescarta), also CD19-directed CART, is approved for adults with relapsed or refractory non-Hodgkin lymphoma after two lines of previous therapy (specifically large-cell lymphoma, primary mediastinal large B-cell lymphoma, and transformed follicular lymphoma). Response rate was 72% (complete, 51%; partial, 21%), with a median duration of response of 9.2 months.¹⁸

Rivaroxaban

Rivaroxaban is a feasible alternative to low-molecular-weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) in cancer patients, according to researchers.

In the SELECT-D trial, cancer patients with VTE received 6 months of treatment with rivaroxaban or the LMWH dalteparin.

Patients who received rivaroxaban had a lower rate of VTE recurrence but higher rates of bleeding than those who received dalteparin.

These results were published in the Journal of Clinical Oncology. The research was supported by Bayer AG.

The trial enrolled 406 patients who had cancer and VTE. Sixty-nine percent of patients were receiving cancer treatment (83% chemotherapy) at baseline, and 58% had metastases.

Patients were randomized to receive dalteparin or rivaroxaban for 6 months. Dalteparin was given at 200 IU/kg daily for the first month, then at 150 IU/kg daily for months 2 to 6. Rivaroxaban was given at 15 mg twice daily for 3 weeks, then at 20 mg once daily for the rest of the treatment period.

The 6-month cumulative VTE recurrence rate was 11% in the dalteparin arm and 4% in the rivaroxaban arm (hazard ratio [HR]=0.43; 95% CI, 0.19 to 0.99).

The 6-month cumulative rate of major bleeding was 4% in the dalteparin arm and 6% in the rivaroxaban arm (HR=1.83; 95% CI, 0.68 to 4.96).

And the 6-month cumulative rate of clinically relevant non-major bleeding was 4% in the dalteparin arm and 13% in the rivaroxaban arm (HR=3.76; 95% CI, 1.63 to 8.69).

The researchers said these results suggest rivaroxaban can be an alternative to LMWH in cancer patients.

“Clinicians were already adopting [rivaroxaban] into practice for non-cancer patients, and now they have data from this study to indicate that this form of treatment is an alternative option for many cancer patients who have a clot,” said study author Annie Young, SRN, PhD, of Warwick Medical School at University of Warwick in Coventry, UK.

“We now need to be sitting down with each one of our cancer patients with VTE, discussing their preference alongside looking at all their clinical details—including whether the cancer lesion is still there, what other medications are being taken, and what other conditions the patient has—so that we can choose the optimal VTE treatment for each patient.”

Rivaroxaban

Rivaroxaban is a feasible alternative to low-molecular-weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) in cancer patients, according to researchers.

In the SELECT-D trial, cancer patients with VTE received 6 months of treatment with rivaroxaban or the LMWH dalteparin.

Patients who received rivaroxaban had a lower rate of VTE recurrence but higher rates of bleeding than those who received dalteparin.

These results were published in the Journal of Clinical Oncology. The research was supported by Bayer AG.

The trial enrolled 406 patients who had cancer and VTE. Sixty-nine percent of patients were receiving cancer treatment (83% chemotherapy) at baseline, and 58% had metastases.

Patients were randomized to receive dalteparin or rivaroxaban for 6 months. Dalteparin was given at 200 IU/kg daily for the first month, then at 150 IU/kg daily for months 2 to 6. Rivaroxaban was given at 15 mg twice daily for 3 weeks, then at 20 mg once daily for the rest of the treatment period.

The 6-month cumulative VTE recurrence rate was 11% in the dalteparin arm and 4% in the rivaroxaban arm (hazard ratio [HR]=0.43; 95% CI, 0.19 to 0.99).

The 6-month cumulative rate of major bleeding was 4% in the dalteparin arm and 6% in the rivaroxaban arm (HR=1.83; 95% CI, 0.68 to 4.96).

And the 6-month cumulative rate of clinically relevant non-major bleeding was 4% in the dalteparin arm and 13% in the rivaroxaban arm (HR=3.76; 95% CI, 1.63 to 8.69).

The researchers said these results suggest rivaroxaban can be an alternative to LMWH in cancer patients.

“Clinicians were already adopting [rivaroxaban] into practice for non-cancer patients, and now they have data from this study to indicate that this form of treatment is an alternative option for many cancer patients who have a clot,” said study author Annie Young, SRN, PhD, of Warwick Medical School at University of Warwick in Coventry, UK.

“We now need to be sitting down with each one of our cancer patients with VTE, discussing their preference alongside looking at all their clinical details—including whether the cancer lesion is still there, what other medications are being taken, and what other conditions the patient has—so that we can choose the optimal VTE treatment for each patient.”

Rivaroxaban

Rivaroxaban is a feasible alternative to low-molecular-weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) in cancer patients, according to researchers.

In the SELECT-D trial, cancer patients with VTE received 6 months of treatment with rivaroxaban or the LMWH dalteparin.

Patients who received rivaroxaban had a lower rate of VTE recurrence but higher rates of bleeding than those who received dalteparin.

These results were published in the Journal of Clinical Oncology. The research was supported by Bayer AG.

The trial enrolled 406 patients who had cancer and VTE. Sixty-nine percent of patients were receiving cancer treatment (83% chemotherapy) at baseline, and 58% had metastases.

Patients were randomized to receive dalteparin or rivaroxaban for 6 months. Dalteparin was given at 200 IU/kg daily for the first month, then at 150 IU/kg daily for months 2 to 6. Rivaroxaban was given at 15 mg twice daily for 3 weeks, then at 20 mg once daily for the rest of the treatment period.

The 6-month cumulative VTE recurrence rate was 11% in the dalteparin arm and 4% in the rivaroxaban arm (hazard ratio [HR]=0.43; 95% CI, 0.19 to 0.99).

The 6-month cumulative rate of major bleeding was 4% in the dalteparin arm and 6% in the rivaroxaban arm (HR=1.83; 95% CI, 0.68 to 4.96).

And the 6-month cumulative rate of clinically relevant non-major bleeding was 4% in the dalteparin arm and 13% in the rivaroxaban arm (HR=3.76; 95% CI, 1.63 to 8.69).

The researchers said these results suggest rivaroxaban can be an alternative to LMWH in cancer patients.

“Clinicians were already adopting [rivaroxaban] into practice for non-cancer patients, and now they have data from this study to indicate that this form of treatment is an alternative option for many cancer patients who have a clot,” said study author Annie Young, SRN, PhD, of Warwick Medical School at University of Warwick in Coventry, UK.

“We now need to be sitting down with each one of our cancer patients with VTE, discussing their preference alongside looking at all their clinical details—including whether the cancer lesion is still there, what other medications are being taken, and what other conditions the patient has—so that we can choose the optimal VTE treatment for each patient.”

Children are increasingly less likely to be exposed to secondhand cigarette smoke in the home, but cannabis seems to be picking up some of the slack, according to Renee D. Goodwin, PhD, and her associates.

Using a study population of 169,259 adults with data available from the National Survey on Drug Use and Health, the researchers found that from 2002 to 2015, the prevalence of parents with children in the home who were also current smokers dropped from 27.6% to 20.2%. By contrast, the rate of cannabis usage increased from 4.9% to 6.8% over the same time period. Overall, the rate of children living in a home with secondhand smoke fell from 29.7% to 23.5%.

Jozef Sedmak/thinkstockphotos.com

[email protected]

SOURCE: Goodwin RD et al. Pediatrics. 2018 May 14. doi: 10.1542/peds.2017-3506.

Children are increasingly less likely to be exposed to secondhand cigarette smoke in the home, but cannabis seems to be picking up some of the slack, according to Renee D. Goodwin, PhD, and her associates.

Using a study population of 169,259 adults with data available from the National Survey on Drug Use and Health, the researchers found that from 2002 to 2015, the prevalence of parents with children in the home who were also current smokers dropped from 27.6% to 20.2%. By contrast, the rate of cannabis usage increased from 4.9% to 6.8% over the same time period. Overall, the rate of children living in a home with secondhand smoke fell from 29.7% to 23.5%.

Jozef Sedmak/thinkstockphotos.com

[email protected]

SOURCE: Goodwin RD et al. Pediatrics. 2018 May 14. doi: 10.1542/peds.2017-3506.

Children are increasingly less likely to be exposed to secondhand cigarette smoke in the home, but cannabis seems to be picking up some of the slack, according to Renee D. Goodwin, PhD, and her associates.

Using a study population of 169,259 adults with data available from the National Survey on Drug Use and Health, the researchers found that from 2002 to 2015, the prevalence of parents with children in the home who were also current smokers dropped from 27.6% to 20.2%. By contrast, the rate of cannabis usage increased from 4.9% to 6.8% over the same time period. Overall, the rate of children living in a home with secondhand smoke fell from 29.7% to 23.5%.

Jozef Sedmak/thinkstockphotos.com

[email protected]

SOURCE: Goodwin RD et al. Pediatrics. 2018 May 14. doi: 10.1542/peds.2017-3506.