Come on. Everyone knows the best part of any conference is meeting up with colleagues, mentors, and friends. So here’s how to do it at (or away from) the annual meeting of the American Association of Clinical Endocrinologists in Boston on May 16-20.

No one is immune from the pull of colleagues past, present, and even future, not even the program chair Vin Tangpricha, MD, who gave the lowdown in an interview on the best venues for getting in touch.

• Thursday Night Chapter Receptions: After the first full day of the meeting, start in the room for your home chapter, then jump to your home state’s chapter, then your training chapter, and so on. This is the easiest and most exciting way at the meeting to connect with your web of colleagues, Dr. Tangpricha suggested enthusiastically. And don’t forget about AACE members from across the globe in the International Chapter Reception, in the biggest (and most fun, by some reports) party room by far. The receptions for all 22 domestic chapters and international members representing 102 countries will be held in the Sheraton Boston Hotel at 6 p.m.
• Wine and Cheese Reception: A Friday night tradition at AACE, from 4:30 p.m. to 6:30 p.m. in the exhibit hall, this offers a needed break at the end of the second full day of sessions to chat with colleagues, see exhibits, and check out posters.
• Women’s Luncheon: Thursday from 12 p.m. to 2:00 p.m. on Level C. In its fifth year, this luncheon has practically outgrown the meeting, with women entering endocrinology outpacing men. Good luck getting tickets; it’s always popular, Dr. Tangpricha said.
  

  SeanPavonePhot/Thinkstock
• College Breakfast With the Masters: This first-time-ever event welcomes and celebrates all past Masters of the American College of Endocrinology (MACEs). In this free, ticketed event on Saturday morning from 6:30 a.m. to 8 a.m., the largest assembly of MACEs ever gathered in the same room will be introduced to newer AACE fellows, who will then have the opportunity to meet with Masters and gather their insights on how to further their own careers in endocrinology, Dr. Tangpricha said.
• President’s Gala: This ticketed event open to members and family is always a great finale to the meeting, held Saturday night after the convocation, is one Dr. Tangpricha always looks forward to. This family-friendly event features food, libations, and live music.
• Social networking: Stay in touch with attendees and endocrinologists following the events and news from the meeting at #AACE2018, and with a Boston Strong–inspired hashtag of #ClinicalEndoStrong.

[email protected]

Come on. Everyone knows the best part of any conference is meeting up with colleagues, mentors, and friends. So here’s how to do it at (or away from) the annual meeting of the American Association of Clinical Endocrinologists in Boston on May 16-20.

No one is immune from the pull of colleagues past, present, and even future, not even the program chair Vin Tangpricha, MD, who gave the lowdown in an interview on the best venues for getting in touch.

• Thursday Night Chapter Receptions: After the first full day of the meeting, start in the room for your home chapter, then jump to your home state’s chapter, then your training chapter, and so on. This is the easiest and most exciting way at the meeting to connect with your web of colleagues, Dr. Tangpricha suggested enthusiastically. And don’t forget about AACE members from across the globe in the International Chapter Reception, in the biggest (and most fun, by some reports) party room by far. The receptions for all 22 domestic chapters and international members representing 102 countries will be held in the Sheraton Boston Hotel at 6 p.m.
• Wine and Cheese Reception: A Friday night tradition at AACE, from 4:30 p.m. to 6:30 p.m. in the exhibit hall, this offers a needed break at the end of the second full day of sessions to chat with colleagues, see exhibits, and check out posters.
• Women’s Luncheon: Thursday from 12 p.m. to 2:00 p.m. on Level C. In its fifth year, this luncheon has practically outgrown the meeting, with women entering endocrinology outpacing men. Good luck getting tickets; it’s always popular, Dr. Tangpricha said.
  

  SeanPavonePhot/Thinkstock
• College Breakfast With the Masters: This first-time-ever event welcomes and celebrates all past Masters of the American College of Endocrinology (MACEs). In this free, ticketed event on Saturday morning from 6:30 a.m. to 8 a.m., the largest assembly of MACEs ever gathered in the same room will be introduced to newer AACE fellows, who will then have the opportunity to meet with Masters and gather their insights on how to further their own careers in endocrinology, Dr. Tangpricha said.
• President’s Gala: This ticketed event open to members and family is always a great finale to the meeting, held Saturday night after the convocation, is one Dr. Tangpricha always looks forward to. This family-friendly event features food, libations, and live music.
• Social networking: Stay in touch with attendees and endocrinologists following the events and news from the meeting at #AACE2018, and with a Boston Strong–inspired hashtag of #ClinicalEndoStrong.

[email protected]

Come on. Everyone knows the best part of any conference is meeting up with colleagues, mentors, and friends. So here’s how to do it at (or away from) the annual meeting of the American Association of Clinical Endocrinologists in Boston on May 16-20.

No one is immune from the pull of colleagues past, present, and even future, not even the program chair Vin Tangpricha, MD, who gave the lowdown in an interview on the best venues for getting in touch.

• Thursday Night Chapter Receptions: After the first full day of the meeting, start in the room for your home chapter, then jump to your home state’s chapter, then your training chapter, and so on. This is the easiest and most exciting way at the meeting to connect with your web of colleagues, Dr. Tangpricha suggested enthusiastically. And don’t forget about AACE members from across the globe in the International Chapter Reception, in the biggest (and most fun, by some reports) party room by far. The receptions for all 22 domestic chapters and international members representing 102 countries will be held in the Sheraton Boston Hotel at 6 p.m.
• Wine and Cheese Reception: A Friday night tradition at AACE, from 4:30 p.m. to 6:30 p.m. in the exhibit hall, this offers a needed break at the end of the second full day of sessions to chat with colleagues, see exhibits, and check out posters.
• Women’s Luncheon: Thursday from 12 p.m. to 2:00 p.m. on Level C. In its fifth year, this luncheon has practically outgrown the meeting, with women entering endocrinology outpacing men. Good luck getting tickets; it’s always popular, Dr. Tangpricha said.
  

  SeanPavonePhot/Thinkstock
• College Breakfast With the Masters: This first-time-ever event welcomes and celebrates all past Masters of the American College of Endocrinology (MACEs). In this free, ticketed event on Saturday morning from 6:30 a.m. to 8 a.m., the largest assembly of MACEs ever gathered in the same room will be introduced to newer AACE fellows, who will then have the opportunity to meet with Masters and gather their insights on how to further their own careers in endocrinology, Dr. Tangpricha said.
• President’s Gala: This ticketed event open to members and family is always a great finale to the meeting, held Saturday night after the convocation, is one Dr. Tangpricha always looks forward to. This family-friendly event features food, libations, and live music.
• Social networking: Stay in touch with attendees and endocrinologists following the events and news from the meeting at #AACE2018, and with a Boston Strong–inspired hashtag of #ClinicalEndoStrong.

[email protected]

Suicide prevention gets ‘standard care’ recommendations Also in today’s edition of the Daily News Podcast, fremanezumab may be an effective episodic migraine treatment, e-cigarette usage has changed, and there is evidence that marketing perks increased opioid prescriptions. Listen to the MDedge Daily News Podcast for all the details ons today’s top news.

Suicide prevention gets ‘standard care’ recommendations Also in today’s edition of the Daily News Podcast, fremanezumab may be an effective episodic migraine treatment, e-cigarette usage has changed, and there is evidence that marketing perks increased opioid prescriptions. Listen to the MDedge Daily News Podcast for all the details ons today’s top news.

Suicide prevention gets ‘standard care’ recommendations Also in today’s edition of the Daily News Podcast, fremanezumab may be an effective episodic migraine treatment, e-cigarette usage has changed, and there is evidence that marketing perks increased opioid prescriptions. Listen to the MDedge Daily News Podcast for all the details ons today’s top news.

Lorenzo Norris, MD, editor in chief of MDedge Psychiatry, sits down with Igor Galynker, MD, PhD, to talk about an evaluation model he and his team created aimed at assessing the risk of imminent suicide. Dr. Galynker also discusses ways clinicians can assess their own personal emotional responses to patients who are at risk.

Lorenzo Norris, MD, editor in chief of MDedge Psychiatry, sits down with Igor Galynker, MD, PhD, to talk about an evaluation model he and his team created aimed at assessing the risk of imminent suicide. Dr. Galynker also discusses ways clinicians can assess their own personal emotional responses to patients who are at risk.

Lorenzo Norris, MD, editor in chief of MDedge Psychiatry, sits down with Igor Galynker, MD, PhD, to talk about an evaluation model he and his team created aimed at assessing the risk of imminent suicide. Dr. Galynker also discusses ways clinicians can assess their own personal emotional responses to patients who are at risk.

Purulent pericarditis is an infection within the pericardial space rarely seen in the modern antibiotic era. Most cases are secondary to another infectious process of bacterial, viral, fungal, or parasitic origin.^1,2 Predisposing factors include malignancy, chronic kidney disease, immunosuppression, diabetes mellitus, and alcohol misuse disorder.¹ Although purulent pericarditis has been described extensively in the literature, it is a challenging diagnosis if it is not initially considered within the differential diagnosis repertoire.^1-4 Most authors agree that this may be because it has become an infrequent diagnosis.^1,2 In addition, purulent pericarditis may have an atypical presentation when compared with a classic case of pericarditis.^2,3 The authors believe that this forgotten entity will be revisited through this case.

Case Presentation

A 66-year-old-man was transferred to Veterans Affairs Caribbean Healthcare System (VACHS) from a community hospital with a diagnosis of community-acquired pneumonia (CAP) and bilateral pleural effusions. Four days prior to arrival at the community hospital, the patient had developed diffuse, watery diarrhea, which resolved in 3 days. After resolution of diarrhea, he began experiencing shortness of breath on exertion that progressed to onset at rest. The patient reported no fever, chills, nausea, vomiting, cough, or contact with others who were not healthy. He had a history of alcohol misuse without liver cirrhosis and reported no chronic diseases or use of medications. The patient had no history of tuberculosis exposure or pneumococcal vaccination, and had a negative interferon gamma release assay.

On admission to the community hospital, the patient was treated for CAP with ceftriaxone and azithromycin. On hospital day 3, the patient developed hypoxemia and an altered mental status. He was started on supplemental oxygen and transferred to the intensive care unit (ICU). Antibiotic therapy consequently was changed to levofloxacin and meropenem. However, no clinical improvement was noted on the following days.

On hospital day 7, the patient developed acute respiratory failure that required mechanical ventilation while being transferred to VACHS via air ambulance. His vital signs on arrival were the following: temperature, 97° F; heart rate, 86 beats/min; blood pressure, 103/61 mm Hg; respiratory rate, 14 breaths/min and SaO₂ of 97%, measured while he breathed supplemental oxygen at an FiO₂ of 0.4. 

Hours after arrival, the patient developed sinus tachycardia and hypotension. A bedside 2D echocardiogram demonstrated a large pericardial effusion with diastolic collapse of the right atrium (Figure 2). 

The patient’s clinical condition improved following drainage of pericardial fluid, with no further need for inotropic support. Antibiotic therapy was changed to vancomycin and meropenem. Initial microbiologic samples from pericardial fluid demonstrated Gram-positive diplococci, suggestive of Streptococcus pneumoniae (S pneumoniae) (Figure 4). Other diagnostic pericardial fluid test results included: WBC count 25,330 cmm, with 99% neutrophils and 1% lymphocytes; total protein, 3.8 mg/dL; glucose, < 2.0 mg/dL,LDH, > 2,500 U/L, potassium hydroxide preparation. The tests found no fungus, and the acid fast bacilli smear revealed no Bacillus. However, the pericardial fluid culture failed to demonstrate growth of any organism. Blood cultures also were negative.

The patient underwent anterior thoracotomy with partial pericardiectomy, and a pericardial tube was left in place connected to drainage. During the procedure, an abundant amount of fibrinous tissue was evacuated from the pericardial space (Figure 5). 

The patient was extubated, pericardial and pleural tubes were removed, and he was transferred to the internal medicine ward 24 days after admission to the ICU. He received in-patient physical rehabilitation while completing a 6-week course of IV antibiotics (vancomycin and meropenem). After completion of therapy, the patient received the pneumococcal polysaccharide vaccination, and an echocardiography was repeated. No significant re-accumulation of pericardial effusion or constrictive pattern was evidenced. The patient was discharged to his out-of-state home, and follow-up was consequently lost.

Discussion

Purulent pericarditis is an infection localized within the pericardial space. Most cases are secondary to an infectious process elsewhere, which could be of bacterial, viral, fungal, or parasitic etiology.¹ Five mechanisms could lead the infecting organism to infect the pericardial space; contiguous spread from intrathoracic site, hematogenous spread, extension from myocardial site, perforating injury or surgery, and extension from a subdiaphragmatic site.¹ Predisposing factors for the development of this condition include malignancy, chronic kidney disease, immunosuppression, diabetes mellitus, and alcohol misuse. Pericarditis is an infection localized within the pericardial space.

Purulent pericarditis has become a rare entity in the antibiotic era.² Prior to the development of antibiotics, most cases were secondary to S pneumoniae.^1,2,5,6 As per Cilloniz and colleagues, about 40% to 50% of all cases of purulent pericarditis are caused by Gram-positive bacteria, mostly S pneumoniae.⁵ In this case study, bacterial culture did not reveal growth of an organism—most likely because the patient had received antibiotics elsewhere. However, Gram-positive cocci were seen within the initial pericardial aspirate. This organism was suspected to have spread contiguously from a pulmonary focus, which also led to pleural effusions.

Since the patient in this case study had no history of thoracic surgery, malignancy, or other immunosuppression, the patient’s history of alcohol misuse was the only predisposing factor for development of purulent pericarditis. Contrary to the common presentation of pericarditis, purulent pericarditis may not have the common clinical findings, such as chest pain, pericardial friction rub, and distended neck veins.^2,3 Furthermore, according to Parikh and colleagues, about 35% of affected patients may have a normal electrocardiogram.² Hence, the diagnosis of purulent pericarditis often is missed because the classic signs of pericarditis are often absent, and other nonspecific symptoms are attributed to initial underlying infection.⁷

A high index of suspicion is needed to diagnose purulent pericarditis. Once a diagnosis is made, initial treatment should consist of prompt drainage of pericardial fluid combined with systemic antibiotic therapy. Vancomycin and a third-generation cephalosporin may be started empirically until results of pericardial fluid cultures become available.³ Drainage can be achieved by pericardiocentesis, pericardiotomy, or pericardiectomy (partial or total).¹ In cases of hemodynamic instability due to cardiac tamponade, sonographically guided pericardiocentesis should be undertaken and an indwelling pericardial catheter left in place.¹ Although this is the simplest and fastest method of evacuation, it may not be effective when dealing with thick, fibrinous fluid. In such cases, intrapericardial fibrinolysis may be considered. This approach may be undertaken early in the process, after drainage insertion, or as salvage therapy, when there has been incomplete evacuation of purulent material or open surgical drainage is not available.

Streptokinase, urokinase, and tissue plasminogen activator have been used for intrapericadial fibrinolysis.¹ However, there is no definite data on dosage or frequency at which these medications should be administered. No matter the therapeutic approach, effective drainage of the pericardial fluid is crucial to avoid the development of pericardial constriction. Constrictive pericarditis occurs when fibrosis and adhesions create a dense pericardium that encases the heart. This causes impaired ventricular filling that can lead eventually to heart failure.⁴ Pericardiectomy is the definitive treatment for constrictive pericarditis.

Conclusion

Although purulent pericarditis has become a rare diagnosis since the development of antibiotics, knowledge of how to identify it is essential since mortality reaches 100% if the diagnosis is missed.⁴ Even when the condition is promptly diagnosed and treated, mortality is 40%, mainly due to cardiac tamponade, septic shock, or constriction.¹ The case presented here illustrates the clinical features associated with this condition. Knowing these features can translate in a successful patient outcome.

Purulent pericarditis is an infection within the pericardial space rarely seen in the modern antibiotic era. Most cases are secondary to another infectious process of bacterial, viral, fungal, or parasitic origin.^1,2 Predisposing factors include malignancy, chronic kidney disease, immunosuppression, diabetes mellitus, and alcohol misuse disorder.¹ Although purulent pericarditis has been described extensively in the literature, it is a challenging diagnosis if it is not initially considered within the differential diagnosis repertoire.^1-4 Most authors agree that this may be because it has become an infrequent diagnosis.^1,2 In addition, purulent pericarditis may have an atypical presentation when compared with a classic case of pericarditis.^2,3 The authors believe that this forgotten entity will be revisited through this case.

Case Presentation

A 66-year-old-man was transferred to Veterans Affairs Caribbean Healthcare System (VACHS) from a community hospital with a diagnosis of community-acquired pneumonia (CAP) and bilateral pleural effusions. Four days prior to arrival at the community hospital, the patient had developed diffuse, watery diarrhea, which resolved in 3 days. After resolution of diarrhea, he began experiencing shortness of breath on exertion that progressed to onset at rest. The patient reported no fever, chills, nausea, vomiting, cough, or contact with others who were not healthy. He had a history of alcohol misuse without liver cirrhosis and reported no chronic diseases or use of medications. The patient had no history of tuberculosis exposure or pneumococcal vaccination, and had a negative interferon gamma release assay.

On admission to the community hospital, the patient was treated for CAP with ceftriaxone and azithromycin. On hospital day 3, the patient developed hypoxemia and an altered mental status. He was started on supplemental oxygen and transferred to the intensive care unit (ICU). Antibiotic therapy consequently was changed to levofloxacin and meropenem. However, no clinical improvement was noted on the following days.

On hospital day 7, the patient developed acute respiratory failure that required mechanical ventilation while being transferred to VACHS via air ambulance. His vital signs on arrival were the following: temperature, 97° F; heart rate, 86 beats/min; blood pressure, 103/61 mm Hg; respiratory rate, 14 breaths/min and SaO₂ of 97%, measured while he breathed supplemental oxygen at an FiO₂ of 0.4. 

Hours after arrival, the patient developed sinus tachycardia and hypotension. A bedside 2D echocardiogram demonstrated a large pericardial effusion with diastolic collapse of the right atrium (Figure 2). 

The patient’s clinical condition improved following drainage of pericardial fluid, with no further need for inotropic support. Antibiotic therapy was changed to vancomycin and meropenem. Initial microbiologic samples from pericardial fluid demonstrated Gram-positive diplococci, suggestive of Streptococcus pneumoniae (S pneumoniae) (Figure 4). Other diagnostic pericardial fluid test results included: WBC count 25,330 cmm, with 99% neutrophils and 1% lymphocytes; total protein, 3.8 mg/dL; glucose, < 2.0 mg/dL,LDH, > 2,500 U/L, potassium hydroxide preparation. The tests found no fungus, and the acid fast bacilli smear revealed no Bacillus. However, the pericardial fluid culture failed to demonstrate growth of any organism. Blood cultures also were negative.

The patient underwent anterior thoracotomy with partial pericardiectomy, and a pericardial tube was left in place connected to drainage. During the procedure, an abundant amount of fibrinous tissue was evacuated from the pericardial space (Figure 5). 

The patient was extubated, pericardial and pleural tubes were removed, and he was transferred to the internal medicine ward 24 days after admission to the ICU. He received in-patient physical rehabilitation while completing a 6-week course of IV antibiotics (vancomycin and meropenem). After completion of therapy, the patient received the pneumococcal polysaccharide vaccination, and an echocardiography was repeated. No significant re-accumulation of pericardial effusion or constrictive pattern was evidenced. The patient was discharged to his out-of-state home, and follow-up was consequently lost.

Discussion

Purulent pericarditis is an infection localized within the pericardial space. Most cases are secondary to an infectious process elsewhere, which could be of bacterial, viral, fungal, or parasitic etiology.¹ Five mechanisms could lead the infecting organism to infect the pericardial space; contiguous spread from intrathoracic site, hematogenous spread, extension from myocardial site, perforating injury or surgery, and extension from a subdiaphragmatic site.¹ Predisposing factors for the development of this condition include malignancy, chronic kidney disease, immunosuppression, diabetes mellitus, and alcohol misuse. Pericarditis is an infection localized within the pericardial space.

Purulent pericarditis has become a rare entity in the antibiotic era.² Prior to the development of antibiotics, most cases were secondary to S pneumoniae.^1,2,5,6 As per Cilloniz and colleagues, about 40% to 50% of all cases of purulent pericarditis are caused by Gram-positive bacteria, mostly S pneumoniae.⁵ In this case study, bacterial culture did not reveal growth of an organism—most likely because the patient had received antibiotics elsewhere. However, Gram-positive cocci were seen within the initial pericardial aspirate. This organism was suspected to have spread contiguously from a pulmonary focus, which also led to pleural effusions.

Since the patient in this case study had no history of thoracic surgery, malignancy, or other immunosuppression, the patient’s history of alcohol misuse was the only predisposing factor for development of purulent pericarditis. Contrary to the common presentation of pericarditis, purulent pericarditis may not have the common clinical findings, such as chest pain, pericardial friction rub, and distended neck veins.^2,3 Furthermore, according to Parikh and colleagues, about 35% of affected patients may have a normal electrocardiogram.² Hence, the diagnosis of purulent pericarditis often is missed because the classic signs of pericarditis are often absent, and other nonspecific symptoms are attributed to initial underlying infection.⁷

A high index of suspicion is needed to diagnose purulent pericarditis. Once a diagnosis is made, initial treatment should consist of prompt drainage of pericardial fluid combined with systemic antibiotic therapy. Vancomycin and a third-generation cephalosporin may be started empirically until results of pericardial fluid cultures become available.³ Drainage can be achieved by pericardiocentesis, pericardiotomy, or pericardiectomy (partial or total).¹ In cases of hemodynamic instability due to cardiac tamponade, sonographically guided pericardiocentesis should be undertaken and an indwelling pericardial catheter left in place.¹ Although this is the simplest and fastest method of evacuation, it may not be effective when dealing with thick, fibrinous fluid. In such cases, intrapericardial fibrinolysis may be considered. This approach may be undertaken early in the process, after drainage insertion, or as salvage therapy, when there has been incomplete evacuation of purulent material or open surgical drainage is not available.

Streptokinase, urokinase, and tissue plasminogen activator have been used for intrapericadial fibrinolysis.¹ However, there is no definite data on dosage or frequency at which these medications should be administered. No matter the therapeutic approach, effective drainage of the pericardial fluid is crucial to avoid the development of pericardial constriction. Constrictive pericarditis occurs when fibrosis and adhesions create a dense pericardium that encases the heart. This causes impaired ventricular filling that can lead eventually to heart failure.⁴ Pericardiectomy is the definitive treatment for constrictive pericarditis.

Conclusion

Although purulent pericarditis has become a rare diagnosis since the development of antibiotics, knowledge of how to identify it is essential since mortality reaches 100% if the diagnosis is missed.⁴ Even when the condition is promptly diagnosed and treated, mortality is 40%, mainly due to cardiac tamponade, septic shock, or constriction.¹ The case presented here illustrates the clinical features associated with this condition. Knowing these features can translate in a successful patient outcome.

Purulent pericarditis is an infection within the pericardial space rarely seen in the modern antibiotic era. Most cases are secondary to another infectious process of bacterial, viral, fungal, or parasitic origin.^1,2 Predisposing factors include malignancy, chronic kidney disease, immunosuppression, diabetes mellitus, and alcohol misuse disorder.¹ Although purulent pericarditis has been described extensively in the literature, it is a challenging diagnosis if it is not initially considered within the differential diagnosis repertoire.^1-4 Most authors agree that this may be because it has become an infrequent diagnosis.^1,2 In addition, purulent pericarditis may have an atypical presentation when compared with a classic case of pericarditis.^2,3 The authors believe that this forgotten entity will be revisited through this case.

Case Presentation

A 66-year-old-man was transferred to Veterans Affairs Caribbean Healthcare System (VACHS) from a community hospital with a diagnosis of community-acquired pneumonia (CAP) and bilateral pleural effusions. Four days prior to arrival at the community hospital, the patient had developed diffuse, watery diarrhea, which resolved in 3 days. After resolution of diarrhea, he began experiencing shortness of breath on exertion that progressed to onset at rest. The patient reported no fever, chills, nausea, vomiting, cough, or contact with others who were not healthy. He had a history of alcohol misuse without liver cirrhosis and reported no chronic diseases or use of medications. The patient had no history of tuberculosis exposure or pneumococcal vaccination, and had a negative interferon gamma release assay.

On admission to the community hospital, the patient was treated for CAP with ceftriaxone and azithromycin. On hospital day 3, the patient developed hypoxemia and an altered mental status. He was started on supplemental oxygen and transferred to the intensive care unit (ICU). Antibiotic therapy consequently was changed to levofloxacin and meropenem. However, no clinical improvement was noted on the following days.

On hospital day 7, the patient developed acute respiratory failure that required mechanical ventilation while being transferred to VACHS via air ambulance. His vital signs on arrival were the following: temperature, 97° F; heart rate, 86 beats/min; blood pressure, 103/61 mm Hg; respiratory rate, 14 breaths/min and SaO₂ of 97%, measured while he breathed supplemental oxygen at an FiO₂ of 0.4. 

Hours after arrival, the patient developed sinus tachycardia and hypotension. A bedside 2D echocardiogram demonstrated a large pericardial effusion with diastolic collapse of the right atrium (Figure 2). 

The patient’s clinical condition improved following drainage of pericardial fluid, with no further need for inotropic support. Antibiotic therapy was changed to vancomycin and meropenem. Initial microbiologic samples from pericardial fluid demonstrated Gram-positive diplococci, suggestive of Streptococcus pneumoniae (S pneumoniae) (Figure 4). Other diagnostic pericardial fluid test results included: WBC count 25,330 cmm, with 99% neutrophils and 1% lymphocytes; total protein, 3.8 mg/dL; glucose, < 2.0 mg/dL,LDH, > 2,500 U/L, potassium hydroxide preparation. The tests found no fungus, and the acid fast bacilli smear revealed no Bacillus. However, the pericardial fluid culture failed to demonstrate growth of any organism. Blood cultures also were negative.

The patient underwent anterior thoracotomy with partial pericardiectomy, and a pericardial tube was left in place connected to drainage. During the procedure, an abundant amount of fibrinous tissue was evacuated from the pericardial space (Figure 5). 

The patient was extubated, pericardial and pleural tubes were removed, and he was transferred to the internal medicine ward 24 days after admission to the ICU. He received in-patient physical rehabilitation while completing a 6-week course of IV antibiotics (vancomycin and meropenem). After completion of therapy, the patient received the pneumococcal polysaccharide vaccination, and an echocardiography was repeated. No significant re-accumulation of pericardial effusion or constrictive pattern was evidenced. The patient was discharged to his out-of-state home, and follow-up was consequently lost.

Discussion

Purulent pericarditis is an infection localized within the pericardial space. Most cases are secondary to an infectious process elsewhere, which could be of bacterial, viral, fungal, or parasitic etiology.¹ Five mechanisms could lead the infecting organism to infect the pericardial space; contiguous spread from intrathoracic site, hematogenous spread, extension from myocardial site, perforating injury or surgery, and extension from a subdiaphragmatic site.¹ Predisposing factors for the development of this condition include malignancy, chronic kidney disease, immunosuppression, diabetes mellitus, and alcohol misuse. Pericarditis is an infection localized within the pericardial space.

Purulent pericarditis has become a rare entity in the antibiotic era.² Prior to the development of antibiotics, most cases were secondary to S pneumoniae.^1,2,5,6 As per Cilloniz and colleagues, about 40% to 50% of all cases of purulent pericarditis are caused by Gram-positive bacteria, mostly S pneumoniae.⁵ In this case study, bacterial culture did not reveal growth of an organism—most likely because the patient had received antibiotics elsewhere. However, Gram-positive cocci were seen within the initial pericardial aspirate. This organism was suspected to have spread contiguously from a pulmonary focus, which also led to pleural effusions.

Since the patient in this case study had no history of thoracic surgery, malignancy, or other immunosuppression, the patient’s history of alcohol misuse was the only predisposing factor for development of purulent pericarditis. Contrary to the common presentation of pericarditis, purulent pericarditis may not have the common clinical findings, such as chest pain, pericardial friction rub, and distended neck veins.^2,3 Furthermore, according to Parikh and colleagues, about 35% of affected patients may have a normal electrocardiogram.² Hence, the diagnosis of purulent pericarditis often is missed because the classic signs of pericarditis are often absent, and other nonspecific symptoms are attributed to initial underlying infection.⁷

A high index of suspicion is needed to diagnose purulent pericarditis. Once a diagnosis is made, initial treatment should consist of prompt drainage of pericardial fluid combined with systemic antibiotic therapy. Vancomycin and a third-generation cephalosporin may be started empirically until results of pericardial fluid cultures become available.³ Drainage can be achieved by pericardiocentesis, pericardiotomy, or pericardiectomy (partial or total).¹ In cases of hemodynamic instability due to cardiac tamponade, sonographically guided pericardiocentesis should be undertaken and an indwelling pericardial catheter left in place.¹ Although this is the simplest and fastest method of evacuation, it may not be effective when dealing with thick, fibrinous fluid. In such cases, intrapericardial fibrinolysis may be considered. This approach may be undertaken early in the process, after drainage insertion, or as salvage therapy, when there has been incomplete evacuation of purulent material or open surgical drainage is not available.

Streptokinase, urokinase, and tissue plasminogen activator have been used for intrapericadial fibrinolysis.¹ However, there is no definite data on dosage or frequency at which these medications should be administered. No matter the therapeutic approach, effective drainage of the pericardial fluid is crucial to avoid the development of pericardial constriction. Constrictive pericarditis occurs when fibrosis and adhesions create a dense pericardium that encases the heart. This causes impaired ventricular filling that can lead eventually to heart failure.⁴ Pericardiectomy is the definitive treatment for constrictive pericarditis.

Conclusion

Although purulent pericarditis has become a rare diagnosis since the development of antibiotics, knowledge of how to identify it is essential since mortality reaches 100% if the diagnosis is missed.⁴ Even when the condition is promptly diagnosed and treated, mortality is 40%, mainly due to cardiac tamponade, septic shock, or constriction.¹ The case presented here illustrates the clinical features associated with this condition. Knowing these features can translate in a successful patient outcome.

Red blood cells

The US Food and Drug Administration (FDA) has approved epoetin alfa-epbx (Retacrit), a biosimilar to epoetin alfa (Epogen/Procrit).

Epoetin alfa-epbx is approved for the treatment of anemia caused by chronic kidney disease, the use of zidovudine in patients with HIV infection, and myelosuppressive chemotherapy in patients who have a minimum of 2 additional months of planned chemotherapy.

Epoetin alfa-epbx is also approved for use before and after surgery to reduce the chance that red blood cell transfusions will be needed because of blood loss during elective, noncardiac, or nonvascular surgery.

As with epoetin alfa, the prescribing information for epoetin alfa-epbx contains a Boxed Warning noting that erythropoiesis-stimulating agents increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.

The FDA granted approval of epoetin alfa-epbx to Hospira Inc., a Pfizer company.

The agency’s approval is based on a review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

This evidence is available in an FDA briefing document on the biologics license application for epoetin alfa-epbx.

Red blood cells

The US Food and Drug Administration (FDA) has approved epoetin alfa-epbx (Retacrit), a biosimilar to epoetin alfa (Epogen/Procrit).

Epoetin alfa-epbx is approved for the treatment of anemia caused by chronic kidney disease, the use of zidovudine in patients with HIV infection, and myelosuppressive chemotherapy in patients who have a minimum of 2 additional months of planned chemotherapy.

Epoetin alfa-epbx is also approved for use before and after surgery to reduce the chance that red blood cell transfusions will be needed because of blood loss during elective, noncardiac, or nonvascular surgery.

As with epoetin alfa, the prescribing information for epoetin alfa-epbx contains a Boxed Warning noting that erythropoiesis-stimulating agents increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.

The FDA granted approval of epoetin alfa-epbx to Hospira Inc., a Pfizer company.

The agency’s approval is based on a review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

This evidence is available in an FDA briefing document on the biologics license application for epoetin alfa-epbx.

Red blood cells

The US Food and Drug Administration (FDA) has approved epoetin alfa-epbx (Retacrit), a biosimilar to epoetin alfa (Epogen/Procrit).

Epoetin alfa-epbx is approved for the treatment of anemia caused by chronic kidney disease, the use of zidovudine in patients with HIV infection, and myelosuppressive chemotherapy in patients who have a minimum of 2 additional months of planned chemotherapy.

Epoetin alfa-epbx is also approved for use before and after surgery to reduce the chance that red blood cell transfusions will be needed because of blood loss during elective, noncardiac, or nonvascular surgery.

As with epoetin alfa, the prescribing information for epoetin alfa-epbx contains a Boxed Warning noting that erythropoiesis-stimulating agents increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.

The FDA granted approval of epoetin alfa-epbx to Hospira Inc., a Pfizer company.

The agency’s approval is based on a review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

This evidence is available in an FDA briefing document on the biologics license application for epoetin alfa-epbx.

Photo by James Gathany

Changes in skin odor can reveal malaria infection in patients with no external symptoms, according to research published in PNAS.

Researchers examined chemical compounds released from the skin of Kenyan children and discovered characteristic patterns in these compounds that identified patients with acute and asymptomatic malaria infections.

“Our previous work in a mouse model found that malaria infection altered the odors of infected mice in ways that made them more attractive to mosquitoes, particularly at a stage of infection where the transmissible stage of the parasite was present at high levels,” said study author Consuelo De Moraes, PhD, of ETH Zurich in Switzerland.

“We also found long-term changes in the odor profiles of infected mice. [So] we had reason to hope that similar changes in human odors might provide biomarkers that could be used for diagnosis.”

To test this theory, Dr De Moraes and her colleagues studied more than 400 Kenyan school children. The researchers collected blood samples as well as samples of volatile substances released from the subjects’ skin.

The team used the blood samples to test for malaria, first via light microscopy and an SD Bioline Rapid Diagnostic Test, then using polymerase chain reaction (PCR) methods to confirm the initial results.

There were 330 subjects who were clearly positive or negative for malaria, and there were 66 subjects who were positive by PCR but negative by microscopy. The researchers compared these findings to results from the skin tests.

To assess the subjects’ skin, the researchers placed each child’s foot and arm into sealed Teflon bags and passed an air current over the skin for about 1 hour. The air was then channeled through special filters that collected the volatile compounds.

Using gas chromatography and mass spectrometry, the researchers then determined the identity and quantity of each compound to generate odor profiles for infected and uninfected children.

Further analysis of these profiles revealed volatile biomarkers that enabled the researchers to accurately identify whether a child was infected with the malaria parasite. Even for asymptomatic infections, the detection rate was close to 100%.

“This high detection rate was encouraging,” Dr De Moraes said. “Initially, we weren’t sure which chemical compounds we should be looking for.”

The researchers noted that malaria infection does not create new chemical compounds, but it alters the amounts of compounds that are already present in the odors of healthy people.

Odor profiles were different for malaria-infected and uninfected subjects, but profiles were also different for patients with acute and asymptomatic infections.

The researchers hope the biomarkers they identified could be used to develop a new tool for the early detection of malaria.

“These new volatile biomarkers are an important first step,” said Mark Mescher, of ETH Zurich. “Now, someone needs to develop an application that can be used cheaply and reliably in the field.”

“In the near-term, our goal is to refine the current findings to find the most reliable and effective biomarkers we can. There is still a lot more work to be done to develop a practical diagnostic assay.”

Photo by James Gathany

Changes in skin odor can reveal malaria infection in patients with no external symptoms, according to research published in PNAS.

Researchers examined chemical compounds released from the skin of Kenyan children and discovered characteristic patterns in these compounds that identified patients with acute and asymptomatic malaria infections.

“Our previous work in a mouse model found that malaria infection altered the odors of infected mice in ways that made them more attractive to mosquitoes, particularly at a stage of infection where the transmissible stage of the parasite was present at high levels,” said study author Consuelo De Moraes, PhD, of ETH Zurich in Switzerland.

“We also found long-term changes in the odor profiles of infected mice. [So] we had reason to hope that similar changes in human odors might provide biomarkers that could be used for diagnosis.”

To test this theory, Dr De Moraes and her colleagues studied more than 400 Kenyan school children. The researchers collected blood samples as well as samples of volatile substances released from the subjects’ skin.

The team used the blood samples to test for malaria, first via light microscopy and an SD Bioline Rapid Diagnostic Test, then using polymerase chain reaction (PCR) methods to confirm the initial results.

There were 330 subjects who were clearly positive or negative for malaria, and there were 66 subjects who were positive by PCR but negative by microscopy. The researchers compared these findings to results from the skin tests.

To assess the subjects’ skin, the researchers placed each child’s foot and arm into sealed Teflon bags and passed an air current over the skin for about 1 hour. The air was then channeled through special filters that collected the volatile compounds.

Using gas chromatography and mass spectrometry, the researchers then determined the identity and quantity of each compound to generate odor profiles for infected and uninfected children.

Further analysis of these profiles revealed volatile biomarkers that enabled the researchers to accurately identify whether a child was infected with the malaria parasite. Even for asymptomatic infections, the detection rate was close to 100%.

“This high detection rate was encouraging,” Dr De Moraes said. “Initially, we weren’t sure which chemical compounds we should be looking for.”

The researchers noted that malaria infection does not create new chemical compounds, but it alters the amounts of compounds that are already present in the odors of healthy people.

Odor profiles were different for malaria-infected and uninfected subjects, but profiles were also different for patients with acute and asymptomatic infections.

The researchers hope the biomarkers they identified could be used to develop a new tool for the early detection of malaria.

“These new volatile biomarkers are an important first step,” said Mark Mescher, of ETH Zurich. “Now, someone needs to develop an application that can be used cheaply and reliably in the field.”

“In the near-term, our goal is to refine the current findings to find the most reliable and effective biomarkers we can. There is still a lot more work to be done to develop a practical diagnostic assay.”

Photo by James Gathany

Changes in skin odor can reveal malaria infection in patients with no external symptoms, according to research published in PNAS.

Researchers examined chemical compounds released from the skin of Kenyan children and discovered characteristic patterns in these compounds that identified patients with acute and asymptomatic malaria infections.

“Our previous work in a mouse model found that malaria infection altered the odors of infected mice in ways that made them more attractive to mosquitoes, particularly at a stage of infection where the transmissible stage of the parasite was present at high levels,” said study author Consuelo De Moraes, PhD, of ETH Zurich in Switzerland.

“We also found long-term changes in the odor profiles of infected mice. [So] we had reason to hope that similar changes in human odors might provide biomarkers that could be used for diagnosis.”

To test this theory, Dr De Moraes and her colleagues studied more than 400 Kenyan school children. The researchers collected blood samples as well as samples of volatile substances released from the subjects’ skin.

The team used the blood samples to test for malaria, first via light microscopy and an SD Bioline Rapid Diagnostic Test, then using polymerase chain reaction (PCR) methods to confirm the initial results.

There were 330 subjects who were clearly positive or negative for malaria, and there were 66 subjects who were positive by PCR but negative by microscopy. The researchers compared these findings to results from the skin tests.

To assess the subjects’ skin, the researchers placed each child’s foot and arm into sealed Teflon bags and passed an air current over the skin for about 1 hour. The air was then channeled through special filters that collected the volatile compounds.

Using gas chromatography and mass spectrometry, the researchers then determined the identity and quantity of each compound to generate odor profiles for infected and uninfected children.

Further analysis of these profiles revealed volatile biomarkers that enabled the researchers to accurately identify whether a child was infected with the malaria parasite. Even for asymptomatic infections, the detection rate was close to 100%.

“This high detection rate was encouraging,” Dr De Moraes said. “Initially, we weren’t sure which chemical compounds we should be looking for.”

The researchers noted that malaria infection does not create new chemical compounds, but it alters the amounts of compounds that are already present in the odors of healthy people.

Odor profiles were different for malaria-infected and uninfected subjects, but profiles were also different for patients with acute and asymptomatic infections.

The researchers hope the biomarkers they identified could be used to develop a new tool for the early detection of malaria.

“These new volatile biomarkers are an important first step,” said Mark Mescher, of ETH Zurich. “Now, someone needs to develop an application that can be used cheaply and reliably in the field.”

“In the near-term, our goal is to refine the current findings to find the most reliable and effective biomarkers we can. There is still a lot more work to be done to develop a practical diagnostic assay.”

Micrograph showing CLL

Phase 1 trial results suggest umbralisib, a PI3Kδ/CK1ε inhibitor, can be safe and active in patients with relapsed or refractory B-cell malignancies.

Researchers said the safety profile of umbralisib “was distinct from that of other PI3Kδ inhibitors,” as it produced few immune-mediated adverse events (AEs).

Umbralisib also produced an objective response rate of 37% in the entire study cohort, 80% in patients with chronic lymphocytic leukemia (CLL), 53% in patients with follicular lymphoma (FL), and 31% in patients with diffuse large B-cell lymphoma (DLBCL).

These results were published in The Lancet Oncology. The study was sponsored by TG Therapeutics, Inc.

The trial enrolled 90 patients between January 17, 2013, and January 14, 2016.

There were 24 patients with CLL, 22 with FL, 16 with DLBCL, 11 with Hodgkin lymphoma, 6 with mantle cell lymphoma, 5 with marginal zone lymphoma, 3 with Waldenstrom’s macroglobulinemia, 2 with T-cell lymphoma, and 1 with hairy cell leukemia.

The median number of prior therapies was 3 (range, 2-5), and 49% of patients were refractory to previous therapy.

Treatment

Patients took umbralisib once daily in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent.

Initially, patients took the drug in a fasting state at doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In April 2014, the researchers did a second dose-escalation with a micronized formulation of umbralisib, taken with food, at doses of 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In August, 2014, all patients who were still on the study transitioned to the 800 mg dose of the micronized formulation. This was the recommended phase 2 dose.

At the data cutoff in November 2016, 44 patients (49%) had received umbralisib for more than 6 cycles, and 23 (26%) had received the drug for more than 12 cycles. Thirteen patients (14%) were still taking umbralisib at the end of the study.

Most patients who stopped treatment did so because of disease progression (n=50, 56%) or AEs (n=9, 10%).

“We are pleased to have treated the first patient ever with umbralisib over 5 years ago and believe it has an important place in the treatment landscape for patients with hematologic malignancies,” said study author Howard A. Burris, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee.

“Several patients from this phase 1 study are still on study today, approaching 5 years of continuous daily therapy, speaking to both the safety and efficacy profile of this unique agent.”

Safety

Dose-limiting toxicities (DLTs) occurred in 4 patients. One DLT was grade 3 maculopapular rash in a patient receiving the 800 mg dose of the initial formulation.

Another DLT was grade 3 hypokalemia in a patient receiving 1800 mg of the initial formulation. A third DLT was grade 3 fatigue, which occurred in 2 patients receiving 1800 mg of the micronized formulation.

Because of these toxicities, the maximum tolerated dose was 1200 mg of the micronized formulation.

The most common treatment-emergent AEs were diarrhea (43%), nausea (42%), and fatigue (31%). The most common grade 3/4 AEs were neutropenia (13%), anemia (9%), and thrombocytopenia (7%).

Serious AEs considered at least possibly related to umbralisib were pneumonia (3%), lung infection (1%), febrile neutropenia (1%), and colitis (2%).

Treatment discontinuation due to AEs considered at least possibly related to umbralisib occurred in 6 patients (7%). Two patients had grade 3 colitis, 2 had increased ALT/AST (grade 1 and grade 4), 1 had grade 2 diarrhea, and 1 had grade 3 fatigue.

There were no treatment-related deaths.

The researchers said the safety profile of umbralisib was distinct from that of other PI3Kδ inhibitors, as patients in this trial had fewer occurrences of autoimmune-like toxicities, such as colitis.

“Preclinically, umbralisib has a very unique profile, selectively inhibiting both PI3Kδ and CK1ε,” said study author Owen O’Connor, MD, PhD, of Columbia Presbyterian Medical Center in New York, New York.

“The clinical results in this paper support our thesis that the differentiated preclinical profile explains the differences seen in the clinic between umbralisib and the other PI3Kδ inhibitors.”

Response

The objective response rate was 37%, with 33 patients achieving a response and 3 patients having a complete response (CR).

Sixteen CLL patients responded (80%), all with partial responses (PRs). Four DLBCL patients responded (31%), all with PRs. And 9 FL patients responded (53%), 2 with CRs.

The remaining CR occurred in a Hodgkin lymphoma patient, and this was the only response in this patient group.

One patient with marginal zone lymphoma had a PR, as did 1 patient with mantle cell lymphoma. All other patients had stable disease or progressed.

The mean duration of response was 13.4 months in the CLL patients, 6.4 months in the DLBCL patients, and 9.3 months in the FL patients.

Micrograph showing CLL

Phase 1 trial results suggest umbralisib, a PI3Kδ/CK1ε inhibitor, can be safe and active in patients with relapsed or refractory B-cell malignancies.

Researchers said the safety profile of umbralisib “was distinct from that of other PI3Kδ inhibitors,” as it produced few immune-mediated adverse events (AEs).

Umbralisib also produced an objective response rate of 37% in the entire study cohort, 80% in patients with chronic lymphocytic leukemia (CLL), 53% in patients with follicular lymphoma (FL), and 31% in patients with diffuse large B-cell lymphoma (DLBCL).

These results were published in The Lancet Oncology. The study was sponsored by TG Therapeutics, Inc.

The trial enrolled 90 patients between January 17, 2013, and January 14, 2016.

There were 24 patients with CLL, 22 with FL, 16 with DLBCL, 11 with Hodgkin lymphoma, 6 with mantle cell lymphoma, 5 with marginal zone lymphoma, 3 with Waldenstrom’s macroglobulinemia, 2 with T-cell lymphoma, and 1 with hairy cell leukemia.

The median number of prior therapies was 3 (range, 2-5), and 49% of patients were refractory to previous therapy.

Treatment

Patients took umbralisib once daily in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent.

Initially, patients took the drug in a fasting state at doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In April 2014, the researchers did a second dose-escalation with a micronized formulation of umbralisib, taken with food, at doses of 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In August, 2014, all patients who were still on the study transitioned to the 800 mg dose of the micronized formulation. This was the recommended phase 2 dose.

At the data cutoff in November 2016, 44 patients (49%) had received umbralisib for more than 6 cycles, and 23 (26%) had received the drug for more than 12 cycles. Thirteen patients (14%) were still taking umbralisib at the end of the study.

Most patients who stopped treatment did so because of disease progression (n=50, 56%) or AEs (n=9, 10%).

“We are pleased to have treated the first patient ever with umbralisib over 5 years ago and believe it has an important place in the treatment landscape for patients with hematologic malignancies,” said study author Howard A. Burris, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee.

“Several patients from this phase 1 study are still on study today, approaching 5 years of continuous daily therapy, speaking to both the safety and efficacy profile of this unique agent.”

Safety

Dose-limiting toxicities (DLTs) occurred in 4 patients. One DLT was grade 3 maculopapular rash in a patient receiving the 800 mg dose of the initial formulation.

Another DLT was grade 3 hypokalemia in a patient receiving 1800 mg of the initial formulation. A third DLT was grade 3 fatigue, which occurred in 2 patients receiving 1800 mg of the micronized formulation.

Because of these toxicities, the maximum tolerated dose was 1200 mg of the micronized formulation.

The most common treatment-emergent AEs were diarrhea (43%), nausea (42%), and fatigue (31%). The most common grade 3/4 AEs were neutropenia (13%), anemia (9%), and thrombocytopenia (7%).

Serious AEs considered at least possibly related to umbralisib were pneumonia (3%), lung infection (1%), febrile neutropenia (1%), and colitis (2%).

Treatment discontinuation due to AEs considered at least possibly related to umbralisib occurred in 6 patients (7%). Two patients had grade 3 colitis, 2 had increased ALT/AST (grade 1 and grade 4), 1 had grade 2 diarrhea, and 1 had grade 3 fatigue.

There were no treatment-related deaths.

The researchers said the safety profile of umbralisib was distinct from that of other PI3Kδ inhibitors, as patients in this trial had fewer occurrences of autoimmune-like toxicities, such as colitis.

“Preclinically, umbralisib has a very unique profile, selectively inhibiting both PI3Kδ and CK1ε,” said study author Owen O’Connor, MD, PhD, of Columbia Presbyterian Medical Center in New York, New York.

“The clinical results in this paper support our thesis that the differentiated preclinical profile explains the differences seen in the clinic between umbralisib and the other PI3Kδ inhibitors.”

Response

The objective response rate was 37%, with 33 patients achieving a response and 3 patients having a complete response (CR).

Sixteen CLL patients responded (80%), all with partial responses (PRs). Four DLBCL patients responded (31%), all with PRs. And 9 FL patients responded (53%), 2 with CRs.

The remaining CR occurred in a Hodgkin lymphoma patient, and this was the only response in this patient group.

One patient with marginal zone lymphoma had a PR, as did 1 patient with mantle cell lymphoma. All other patients had stable disease or progressed.

The mean duration of response was 13.4 months in the CLL patients, 6.4 months in the DLBCL patients, and 9.3 months in the FL patients.

Micrograph showing CLL

Phase 1 trial results suggest umbralisib, a PI3Kδ/CK1ε inhibitor, can be safe and active in patients with relapsed or refractory B-cell malignancies.

Researchers said the safety profile of umbralisib “was distinct from that of other PI3Kδ inhibitors,” as it produced few immune-mediated adverse events (AEs).

Umbralisib also produced an objective response rate of 37% in the entire study cohort, 80% in patients with chronic lymphocytic leukemia (CLL), 53% in patients with follicular lymphoma (FL), and 31% in patients with diffuse large B-cell lymphoma (DLBCL).

These results were published in The Lancet Oncology. The study was sponsored by TG Therapeutics, Inc.

The trial enrolled 90 patients between January 17, 2013, and January 14, 2016.

There were 24 patients with CLL, 22 with FL, 16 with DLBCL, 11 with Hodgkin lymphoma, 6 with mantle cell lymphoma, 5 with marginal zone lymphoma, 3 with Waldenstrom’s macroglobulinemia, 2 with T-cell lymphoma, and 1 with hairy cell leukemia.

The median number of prior therapies was 3 (range, 2-5), and 49% of patients were refractory to previous therapy.

Treatment

Patients took umbralisib once daily in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent.

Initially, patients took the drug in a fasting state at doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In April 2014, the researchers did a second dose-escalation with a micronized formulation of umbralisib, taken with food, at doses of 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In August, 2014, all patients who were still on the study transitioned to the 800 mg dose of the micronized formulation. This was the recommended phase 2 dose.

At the data cutoff in November 2016, 44 patients (49%) had received umbralisib for more than 6 cycles, and 23 (26%) had received the drug for more than 12 cycles. Thirteen patients (14%) were still taking umbralisib at the end of the study.

Most patients who stopped treatment did so because of disease progression (n=50, 56%) or AEs (n=9, 10%).

“We are pleased to have treated the first patient ever with umbralisib over 5 years ago and believe it has an important place in the treatment landscape for patients with hematologic malignancies,” said study author Howard A. Burris, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee.

“Several patients from this phase 1 study are still on study today, approaching 5 years of continuous daily therapy, speaking to both the safety and efficacy profile of this unique agent.”

Safety

Dose-limiting toxicities (DLTs) occurred in 4 patients. One DLT was grade 3 maculopapular rash in a patient receiving the 800 mg dose of the initial formulation.

Another DLT was grade 3 hypokalemia in a patient receiving 1800 mg of the initial formulation. A third DLT was grade 3 fatigue, which occurred in 2 patients receiving 1800 mg of the micronized formulation.

Because of these toxicities, the maximum tolerated dose was 1200 mg of the micronized formulation.

The most common treatment-emergent AEs were diarrhea (43%), nausea (42%), and fatigue (31%). The most common grade 3/4 AEs were neutropenia (13%), anemia (9%), and thrombocytopenia (7%).

Serious AEs considered at least possibly related to umbralisib were pneumonia (3%), lung infection (1%), febrile neutropenia (1%), and colitis (2%).

Treatment discontinuation due to AEs considered at least possibly related to umbralisib occurred in 6 patients (7%). Two patients had grade 3 colitis, 2 had increased ALT/AST (grade 1 and grade 4), 1 had grade 2 diarrhea, and 1 had grade 3 fatigue.

There were no treatment-related deaths.

The researchers said the safety profile of umbralisib was distinct from that of other PI3Kδ inhibitors, as patients in this trial had fewer occurrences of autoimmune-like toxicities, such as colitis.

“Preclinically, umbralisib has a very unique profile, selectively inhibiting both PI3Kδ and CK1ε,” said study author Owen O’Connor, MD, PhD, of Columbia Presbyterian Medical Center in New York, New York.

“The clinical results in this paper support our thesis that the differentiated preclinical profile explains the differences seen in the clinic between umbralisib and the other PI3Kδ inhibitors.”

Response

The objective response rate was 37%, with 33 patients achieving a response and 3 patients having a complete response (CR).

Sixteen CLL patients responded (80%), all with partial responses (PRs). Four DLBCL patients responded (31%), all with PRs. And 9 FL patients responded (53%), 2 with CRs.

The remaining CR occurred in a Hodgkin lymphoma patient, and this was the only response in this patient group.

One patient with marginal zone lymphoma had a PR, as did 1 patient with mantle cell lymphoma. All other patients had stable disease or progressed.

The mean duration of response was 13.4 months in the CLL patients, 6.4 months in the DLBCL patients, and 9.3 months in the FL patients.

Annual encounters with suicidal ideation and attempts at children’s hospitals more than doubled during 2008-2015, according to a retrospective analysis by Gregory Plemmons, MD, of Vanderbilt University, Nashville, Tenn., and his coinvestigators.

The researchers also found that suicidal ideation and suicide attempts occurred more often during the spring and fall than in the summer, coinciding with the academic school year, highlighting “the need for further research in the role that schools may play.”

KatarzynaBialasiewicz/Thinkstock

[email protected]

SOURCE: Plemmons G et al. Pediatrics. 2018;141(6):e20172426.

Annual encounters with suicidal ideation and attempts at children’s hospitals more than doubled during 2008-2015, according to a retrospective analysis by Gregory Plemmons, MD, of Vanderbilt University, Nashville, Tenn., and his coinvestigators.

The researchers also found that suicidal ideation and suicide attempts occurred more often during the spring and fall than in the summer, coinciding with the academic school year, highlighting “the need for further research in the role that schools may play.”

KatarzynaBialasiewicz/Thinkstock

[email protected]

SOURCE: Plemmons G et al. Pediatrics. 2018;141(6):e20172426.

Annual encounters with suicidal ideation and attempts at children’s hospitals more than doubled during 2008-2015, according to a retrospective analysis by Gregory Plemmons, MD, of Vanderbilt University, Nashville, Tenn., and his coinvestigators.

The researchers also found that suicidal ideation and suicide attempts occurred more often during the spring and fall than in the summer, coinciding with the academic school year, highlighting “the need for further research in the role that schools may play.”

KatarzynaBialasiewicz/Thinkstock

[email protected]

SOURCE: Plemmons G et al. Pediatrics. 2018;141(6):e20172426.

We want to hear from you! If you’re in New Orleans for the AAPA conference, stop by the Clinician Reviews booth (#917) in the Exhibit Hall! We’re there from 9 am to 5 pm on Monday, May 21, and from 9 am to 2:30 pm on Tuesday, May 22.

At our booth, you can:

• Get a stamp for your Medical Pursuit card
• Meet our PA Editor-in-Chief, Randy D. Danielsen, PhD, PA, DFAAPA, on Monday (May 21) from 1 to 2:30 pm and Tuesday (May 22) from 11 am to 12:30 pm
• Talk to the editors about writing a clinical manuscript for publication
• Provide feedback on anything you’ve read in our print issue, on our website, or via our e-newsletters

We’re looking forward to chatting with you and learning how Clinician Reviews can be of continuing value to you in your practice!

We want to hear from you! If you’re in New Orleans for the AAPA conference, stop by the Clinician Reviews booth (#917) in the Exhibit Hall! We’re there from 9 am to 5 pm on Monday, May 21, and from 9 am to 2:30 pm on Tuesday, May 22.

At our booth, you can:

• Get a stamp for your Medical Pursuit card
• Meet our PA Editor-in-Chief, Randy D. Danielsen, PhD, PA, DFAAPA, on Monday (May 21) from 1 to 2:30 pm and Tuesday (May 22) from 11 am to 12:30 pm
• Talk to the editors about writing a clinical manuscript for publication
• Provide feedback on anything you’ve read in our print issue, on our website, or via our e-newsletters

We’re looking forward to chatting with you and learning how Clinician Reviews can be of continuing value to you in your practice!

We want to hear from you! If you’re in New Orleans for the AAPA conference, stop by the Clinician Reviews booth (#917) in the Exhibit Hall! We’re there from 9 am to 5 pm on Monday, May 21, and from 9 am to 2:30 pm on Tuesday, May 22.

At our booth, you can:

• Get a stamp for your Medical Pursuit card
• Meet our PA Editor-in-Chief, Randy D. Danielsen, PhD, PA, DFAAPA, on Monday (May 21) from 1 to 2:30 pm and Tuesday (May 22) from 11 am to 12:30 pm
• Talk to the editors about writing a clinical manuscript for publication
• Provide feedback on anything you’ve read in our print issue, on our website, or via our e-newsletters

We’re looking forward to chatting with you and learning how Clinician Reviews can be of continuing value to you in your practice!

ANSWER

The image shows a large, convex hyperdensity within the left parietal region. This is a textbook image of an acute epidural hematoma. There is considerable mass effect and evidence of left-to-right shift. Windowing shows an underlying fracture, which is typically associated with these types of hemorrhages.

There is also evidence of a right-side concave hyperdensity, consistent with an acute subdural hematoma. Typically, this is referred to as a contrecoup injury.

The patient was transported to the operating room for an emergent left craniotomy for epidural evacuation; he recovered uneventfully.

ANSWER

The image shows a large, convex hyperdensity within the left parietal region. This is a textbook image of an acute epidural hematoma. There is considerable mass effect and evidence of left-to-right shift. Windowing shows an underlying fracture, which is typically associated with these types of hemorrhages.

There is also evidence of a right-side concave hyperdensity, consistent with an acute subdural hematoma. Typically, this is referred to as a contrecoup injury.

The patient was transported to the operating room for an emergent left craniotomy for epidural evacuation; he recovered uneventfully.

ANSWER

The image shows a large, convex hyperdensity within the left parietal region. This is a textbook image of an acute epidural hematoma. There is considerable mass effect and evidence of left-to-right shift. Windowing shows an underlying fracture, which is typically associated with these types of hemorrhages.

There is also evidence of a right-side concave hyperdensity, consistent with an acute subdural hematoma. Typically, this is referred to as a contrecoup injury.

The patient was transported to the operating room for an emergent left craniotomy for epidural evacuation; he recovered uneventfully.