Lab mice

Photo by Aaron Logan

Research in mice suggests it’s feasible to use an immunotherapy conditioning regimen rather than radiation or chemotherapy prior to hematopoietic stem cell transplant (HSCT).

Investigators found that combining an antibody against the HSC receptor c-Kit with a CD47-blocking therapy could eliminate host HSCs and allow for successful engraftment of donor HSCs in immunocompetent recipient mice.

Adding T-cell-depleting antibodies to the mix allowed for robust HSC engraftment in a clinically relevant model of allogeneic HSCT.

Irving Weissman, MD, of Stanford University School of Medicine in California, and his colleagues conducted this research and reported the results in Science Translational Medicine.

The researchers first found that ACK2, an antibody against c-Kit, successfully depleted HSCs in immune-deficient mice.

“However, this antibody alone would not be effective in immune-competent recipients, who represent a majority of potential bone marrow transplant recipients,” said study author Akanksha Chhabra, PhD, of Stanford University School of Medicine.

So the researchers sought to enhance the effectiveness of ACK2 by combining it with antibodies or biologic agents that block CD47. They found that blocking CD47—particularly with an antagonist known as CV1mb—liberated macrophages to engulf target cells.

In this way, the immune system effectively depleted host HSCs in the immunocompetent mice, clearing the way for donor HSCs to take up residence in the bone marrow.

Finally, the researchers set out to determine whether conditioning with an anti-c-Kit antibody and CD47-blocking therapy could be extended to a clinically relevant model of allogeneic HSCT, in which the donor and recipient are matched through human leukocyte antigen alleles but mismatched at minor histocompatibility complex (mHC) antigens.

So the team conditioned mice with either ACK2 and CV1mb or ACK2 and the anti-CD47 antibody MIAP410. And they achieved immune ablation with T-cell-depleting antibodies—GK1.5 (anti-CD4) and YTS169.4 (anti-CD8). The mice then received mHC-mismatched HSCs.

The researchers found that either conditioning regimen, when combined with a T-cell-depleting regimen, resulted in substantial granulocyte, B-cell, T-cell, and NK-cell chimerism, as well as HSC engraftment in the bone marrow.

The success of these techniques in mice raises the researchers’ hopes that similar techniques will succeed in humans.

“If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20% to effectively 0,” said study author Judith Shizuru, MD, PhD, of Stanford University School of Medicine.

“If and when this is accomplished, it will be a whole new era in disease treatment and regenerative medicine,” Dr Weissman said.

Lab mice

Photo by Aaron Logan

Research in mice suggests it’s feasible to use an immunotherapy conditioning regimen rather than radiation or chemotherapy prior to hematopoietic stem cell transplant (HSCT).

Investigators found that combining an antibody against the HSC receptor c-Kit with a CD47-blocking therapy could eliminate host HSCs and allow for successful engraftment of donor HSCs in immunocompetent recipient mice.

Adding T-cell-depleting antibodies to the mix allowed for robust HSC engraftment in a clinically relevant model of allogeneic HSCT.

Irving Weissman, MD, of Stanford University School of Medicine in California, and his colleagues conducted this research and reported the results in Science Translational Medicine.

The researchers first found that ACK2, an antibody against c-Kit, successfully depleted HSCs in immune-deficient mice.

“However, this antibody alone would not be effective in immune-competent recipients, who represent a majority of potential bone marrow transplant recipients,” said study author Akanksha Chhabra, PhD, of Stanford University School of Medicine.

So the researchers sought to enhance the effectiveness of ACK2 by combining it with antibodies or biologic agents that block CD47. They found that blocking CD47—particularly with an antagonist known as CV1mb—liberated macrophages to engulf target cells.

In this way, the immune system effectively depleted host HSCs in the immunocompetent mice, clearing the way for donor HSCs to take up residence in the bone marrow.

Finally, the researchers set out to determine whether conditioning with an anti-c-Kit antibody and CD47-blocking therapy could be extended to a clinically relevant model of allogeneic HSCT, in which the donor and recipient are matched through human leukocyte antigen alleles but mismatched at minor histocompatibility complex (mHC) antigens.

So the team conditioned mice with either ACK2 and CV1mb or ACK2 and the anti-CD47 antibody MIAP410. And they achieved immune ablation with T-cell-depleting antibodies—GK1.5 (anti-CD4) and YTS169.4 (anti-CD8). The mice then received mHC-mismatched HSCs.

The researchers found that either conditioning regimen, when combined with a T-cell-depleting regimen, resulted in substantial granulocyte, B-cell, T-cell, and NK-cell chimerism, as well as HSC engraftment in the bone marrow.

The success of these techniques in mice raises the researchers’ hopes that similar techniques will succeed in humans.

“If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20% to effectively 0,” said study author Judith Shizuru, MD, PhD, of Stanford University School of Medicine.

“If and when this is accomplished, it will be a whole new era in disease treatment and regenerative medicine,” Dr Weissman said.

Lab mice

Photo by Aaron Logan

Research in mice suggests it’s feasible to use an immunotherapy conditioning regimen rather than radiation or chemotherapy prior to hematopoietic stem cell transplant (HSCT).

Investigators found that combining an antibody against the HSC receptor c-Kit with a CD47-blocking therapy could eliminate host HSCs and allow for successful engraftment of donor HSCs in immunocompetent recipient mice.

Adding T-cell-depleting antibodies to the mix allowed for robust HSC engraftment in a clinically relevant model of allogeneic HSCT.

Irving Weissman, MD, of Stanford University School of Medicine in California, and his colleagues conducted this research and reported the results in Science Translational Medicine.

The researchers first found that ACK2, an antibody against c-Kit, successfully depleted HSCs in immune-deficient mice.

“However, this antibody alone would not be effective in immune-competent recipients, who represent a majority of potential bone marrow transplant recipients,” said study author Akanksha Chhabra, PhD, of Stanford University School of Medicine.

So the researchers sought to enhance the effectiveness of ACK2 by combining it with antibodies or biologic agents that block CD47. They found that blocking CD47—particularly with an antagonist known as CV1mb—liberated macrophages to engulf target cells.

In this way, the immune system effectively depleted host HSCs in the immunocompetent mice, clearing the way for donor HSCs to take up residence in the bone marrow.

Finally, the researchers set out to determine whether conditioning with an anti-c-Kit antibody and CD47-blocking therapy could be extended to a clinically relevant model of allogeneic HSCT, in which the donor and recipient are matched through human leukocyte antigen alleles but mismatched at minor histocompatibility complex (mHC) antigens.

So the team conditioned mice with either ACK2 and CV1mb or ACK2 and the anti-CD47 antibody MIAP410. And they achieved immune ablation with T-cell-depleting antibodies—GK1.5 (anti-CD4) and YTS169.4 (anti-CD8). The mice then received mHC-mismatched HSCs.

The researchers found that either conditioning regimen, when combined with a T-cell-depleting regimen, resulted in substantial granulocyte, B-cell, T-cell, and NK-cell chimerism, as well as HSC engraftment in the bone marrow.

The success of these techniques in mice raises the researchers’ hopes that similar techniques will succeed in humans.

“If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20% to effectively 0,” said study author Judith Shizuru, MD, PhD, of Stanford University School of Medicine.

“If and when this is accomplished, it will be a whole new era in disease treatment and regenerative medicine,” Dr Weissman said.

Blood sample collection

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for the xMAP® MultiFLEX™ Zika RNA Assay.

This multiplex nucleic acid test is designed to detect Zika virus RNA in blood serum, plasma, or urine (collected alongside a patient-matched serum or plasma specimen).

The xMAP® MultiFLEX™ Zika RNA Assay is available for purchase by laboratories that are certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high complexity tests.

The assay uses the Luminex® 100/200™ analyzer, MAGPIX® system, or other authorized instruments to simultaneously test for 6 genetic targets of the Zika virus.

The xMAP® MultiFLEX™ Zika RNA Assay was designed by GenArraytion, Inc. and is marketed by Luminex Corporation.

For more information on the test, see the fact sheet for healthcare providers on the Luminex website.

About the EUA

The EUA does not mean the xMAP® MultiFLEX™ Zika RNA Assay is FDA cleared or approved.

An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.

The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

This means the xMAP® MultiFLEX™ Zika RNA Assay is only authorized as long as circumstances exist to justify the authorization of the emergency use of in vitro diagnostics for the detection of Zika virus, unless the authorization is terminated or revoked sooner.

Blood sample collection

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for the xMAP® MultiFLEX™ Zika RNA Assay.

This multiplex nucleic acid test is designed to detect Zika virus RNA in blood serum, plasma, or urine (collected alongside a patient-matched serum or plasma specimen).

The xMAP® MultiFLEX™ Zika RNA Assay is available for purchase by laboratories that are certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high complexity tests.

The assay uses the Luminex® 100/200™ analyzer, MAGPIX® system, or other authorized instruments to simultaneously test for 6 genetic targets of the Zika virus.

The xMAP® MultiFLEX™ Zika RNA Assay was designed by GenArraytion, Inc. and is marketed by Luminex Corporation.

For more information on the test, see the fact sheet for healthcare providers on the Luminex website.

About the EUA

The EUA does not mean the xMAP® MultiFLEX™ Zika RNA Assay is FDA cleared or approved.

An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.

The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

This means the xMAP® MultiFLEX™ Zika RNA Assay is only authorized as long as circumstances exist to justify the authorization of the emergency use of in vitro diagnostics for the detection of Zika virus, unless the authorization is terminated or revoked sooner.

Blood sample collection

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for the xMAP® MultiFLEX™ Zika RNA Assay.

This multiplex nucleic acid test is designed to detect Zika virus RNA in blood serum, plasma, or urine (collected alongside a patient-matched serum or plasma specimen).

The xMAP® MultiFLEX™ Zika RNA Assay is available for purchase by laboratories that are certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high complexity tests.

The assay uses the Luminex® 100/200™ analyzer, MAGPIX® system, or other authorized instruments to simultaneously test for 6 genetic targets of the Zika virus.

The xMAP® MultiFLEX™ Zika RNA Assay was designed by GenArraytion, Inc. and is marketed by Luminex Corporation.

For more information on the test, see the fact sheet for healthcare providers on the Luminex website.

About the EUA

The EUA does not mean the xMAP® MultiFLEX™ Zika RNA Assay is FDA cleared or approved.

An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.

The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

This means the xMAP® MultiFLEX™ Zika RNA Assay is only authorized as long as circumstances exist to justify the authorization of the emergency use of in vitro diagnostics for the detection of Zika virus, unless the authorization is terminated or revoked sooner.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved granisetron extended-release injection (Sustol®) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adults.

Extended-release granisetron is a serotonin-3 (5-HT3) receptor antagonist that utilizes Biochronomer® polymer-based drug delivery technology to maintain therapeutic levels of granisetron for at least 5 days, covering both the acute and delayed phases of CINV.

The product is intended for use in combination with other anti-emetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.

“Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control,” said Ralph V. Boccia, MD, of the Center for Cancer and Blood Disorders in Bethesda, Maryland.

“In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. Sustol, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days.”

Extended-release granisetron (formerly known as APF530) is a product of Heron Therapeutics, Inc. The US commercial launch of the drug is planned for the fourth quarter of 2016.

Phase 3 trials

The global phase 3 development program of extended-release granisetron consisted of 2 large, guideline-based clinical trials of more than 2000 cancer patients.

In one trial, researchers compared extended-release granisetron to palonosetron for the prevention of acute and delayed CINV after MEC or highly emetogenic chemotherapy (HEC).

Results suggested extended-release granisetron was non-inferior to palonosetron. The most common adverse events observed in patients receiving granisetron were injection-site reactions and constipation.

In another trial, researchers compared extended-release granisetron to ondansetron for control of delayed CINV after HEC. Patients received extended-release granisetron, dexamethasone, and fosaprepitant or ondansetron, dexamethasone, and fosaprepitant.

A higher percentage of patients in the granisetron arm had delayed-phase complete response. The incidence of treatment-emergent adverse events was similar between the treatment arms.

“The Sustol clinical trial populations and results are highly representative of cancer patients in our real-world clinical practice,” said Jeffrey Vacirca, MD, of North Shore Hematology Oncology Associates in East Setauket, New York.

“Use of MEC regimens is widespread, and AC-based regimens are among the most commonly prescribed highly emetogenic chemotherapy regimens. The most significant challenge for my breast cancer patients receiving AC is chemotherapy-induced nausea and vomiting. Sustol represents a better option to manage this devastating side effect of therapy.”

For more details on the drug, access the full prescribing information at www.SUSTOL.com.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved granisetron extended-release injection (Sustol®) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adults.

Extended-release granisetron is a serotonin-3 (5-HT3) receptor antagonist that utilizes Biochronomer® polymer-based drug delivery technology to maintain therapeutic levels of granisetron for at least 5 days, covering both the acute and delayed phases of CINV.

The product is intended for use in combination with other anti-emetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.

“Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control,” said Ralph V. Boccia, MD, of the Center for Cancer and Blood Disorders in Bethesda, Maryland.

“In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. Sustol, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days.”

Extended-release granisetron (formerly known as APF530) is a product of Heron Therapeutics, Inc. The US commercial launch of the drug is planned for the fourth quarter of 2016.

Phase 3 trials

The global phase 3 development program of extended-release granisetron consisted of 2 large, guideline-based clinical trials of more than 2000 cancer patients.

In one trial, researchers compared extended-release granisetron to palonosetron for the prevention of acute and delayed CINV after MEC or highly emetogenic chemotherapy (HEC).

Results suggested extended-release granisetron was non-inferior to palonosetron. The most common adverse events observed in patients receiving granisetron were injection-site reactions and constipation.

In another trial, researchers compared extended-release granisetron to ondansetron for control of delayed CINV after HEC. Patients received extended-release granisetron, dexamethasone, and fosaprepitant or ondansetron, dexamethasone, and fosaprepitant.

A higher percentage of patients in the granisetron arm had delayed-phase complete response. The incidence of treatment-emergent adverse events was similar between the treatment arms.

“The Sustol clinical trial populations and results are highly representative of cancer patients in our real-world clinical practice,” said Jeffrey Vacirca, MD, of North Shore Hematology Oncology Associates in East Setauket, New York.

“Use of MEC regimens is widespread, and AC-based regimens are among the most commonly prescribed highly emetogenic chemotherapy regimens. The most significant challenge for my breast cancer patients receiving AC is chemotherapy-induced nausea and vomiting. Sustol represents a better option to manage this devastating side effect of therapy.”

For more details on the drug, access the full prescribing information at www.SUSTOL.com.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved granisetron extended-release injection (Sustol®) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adults.

Extended-release granisetron is a serotonin-3 (5-HT3) receptor antagonist that utilizes Biochronomer® polymer-based drug delivery technology to maintain therapeutic levels of granisetron for at least 5 days, covering both the acute and delayed phases of CINV.

The product is intended for use in combination with other anti-emetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.

“Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control,” said Ralph V. Boccia, MD, of the Center for Cancer and Blood Disorders in Bethesda, Maryland.

“In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. Sustol, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days.”

Extended-release granisetron (formerly known as APF530) is a product of Heron Therapeutics, Inc. The US commercial launch of the drug is planned for the fourth quarter of 2016.

Phase 3 trials

The global phase 3 development program of extended-release granisetron consisted of 2 large, guideline-based clinical trials of more than 2000 cancer patients.

In one trial, researchers compared extended-release granisetron to palonosetron for the prevention of acute and delayed CINV after MEC or highly emetogenic chemotherapy (HEC).

Results suggested extended-release granisetron was non-inferior to palonosetron. The most common adverse events observed in patients receiving granisetron were injection-site reactions and constipation.

In another trial, researchers compared extended-release granisetron to ondansetron for control of delayed CINV after HEC. Patients received extended-release granisetron, dexamethasone, and fosaprepitant or ondansetron, dexamethasone, and fosaprepitant.

A higher percentage of patients in the granisetron arm had delayed-phase complete response. The incidence of treatment-emergent adverse events was similar between the treatment arms.

“The Sustol clinical trial populations and results are highly representative of cancer patients in our real-world clinical practice,” said Jeffrey Vacirca, MD, of North Shore Hematology Oncology Associates in East Setauket, New York.

“Use of MEC regimens is widespread, and AC-based regimens are among the most commonly prescribed highly emetogenic chemotherapy regimens. The most significant challenge for my breast cancer patients receiving AC is chemotherapy-induced nausea and vomiting. Sustol represents a better option to manage this devastating side effect of therapy.”

For more details on the drug, access the full prescribing information at www.SUSTOL.com.

Platelets (blue) in a thrombus

Image by Andre E.X. Brown

Researchers say they have determined how procoagulant platelets develop.

One of the mysteries in the field of thrombosis and hemostasis is how platelets are divided into two kinds when activated—“ordinary” platelets capable of aggregation and “super-activated,” procoagulant platelets.

The new study suggests that, to become super-activated, platelets must die. And the platelets need mitochondria to commit suicide.

Researchers were able to show how this programmed death—mitochondrial necrosis—follows a chain of events that lead to the platelets’ transition to a super-activated state.

“It was not clear before how a platelet makes the decision of what type to become,” said study author Mikhail Panteleev, of Lomonosov Moscow State University in Russia.

“We have deciphered the sequence of events: how the signal goes within the platelet and how the cell decides to die.”

Panteleev and his colleagues described these events in the Journal of Thrombosis and Haemostasis.

The team noted that platelets have many activators, but the chief among them are collagen, ADP, and thrombin.

Platelets detect different concentrations of an activator and respond with a varying frequency of calcium impulses in the cytoplasm.

The platelets’ mitochondria absorb and store the calcium, and when its concentration exceeds the critical level, the process of mitochondrial necrosis starts.

Calcium and reactive oxygen species are released from mitochondria, ATPases begin to destroy ATP instead of synthesizing it, the cell cytoskeleton collapses, and the platelets greatly increase in size.

As a result, at the outer membrane of the enlarged platelets, a lipid called phosphatidylserine appears, which is responsible for rapid blood clotting. And all this happens in seconds.

Platelets (blue) in a thrombus

Image by Andre E.X. Brown

Researchers say they have determined how procoagulant platelets develop.

One of the mysteries in the field of thrombosis and hemostasis is how platelets are divided into two kinds when activated—“ordinary” platelets capable of aggregation and “super-activated,” procoagulant platelets.

The new study suggests that, to become super-activated, platelets must die. And the platelets need mitochondria to commit suicide.

Researchers were able to show how this programmed death—mitochondrial necrosis—follows a chain of events that lead to the platelets’ transition to a super-activated state.

“It was not clear before how a platelet makes the decision of what type to become,” said study author Mikhail Panteleev, of Lomonosov Moscow State University in Russia.

“We have deciphered the sequence of events: how the signal goes within the platelet and how the cell decides to die.”

Panteleev and his colleagues described these events in the Journal of Thrombosis and Haemostasis.

The team noted that platelets have many activators, but the chief among them are collagen, ADP, and thrombin.

Platelets detect different concentrations of an activator and respond with a varying frequency of calcium impulses in the cytoplasm.

The platelets’ mitochondria absorb and store the calcium, and when its concentration exceeds the critical level, the process of mitochondrial necrosis starts.

Calcium and reactive oxygen species are released from mitochondria, ATPases begin to destroy ATP instead of synthesizing it, the cell cytoskeleton collapses, and the platelets greatly increase in size.

As a result, at the outer membrane of the enlarged platelets, a lipid called phosphatidylserine appears, which is responsible for rapid blood clotting. And all this happens in seconds.

Platelets (blue) in a thrombus

Image by Andre E.X. Brown

Researchers say they have determined how procoagulant platelets develop.

One of the mysteries in the field of thrombosis and hemostasis is how platelets are divided into two kinds when activated—“ordinary” platelets capable of aggregation and “super-activated,” procoagulant platelets.

The new study suggests that, to become super-activated, platelets must die. And the platelets need mitochondria to commit suicide.

Researchers were able to show how this programmed death—mitochondrial necrosis—follows a chain of events that lead to the platelets’ transition to a super-activated state.

“It was not clear before how a platelet makes the decision of what type to become,” said study author Mikhail Panteleev, of Lomonosov Moscow State University in Russia.

“We have deciphered the sequence of events: how the signal goes within the platelet and how the cell decides to die.”

Panteleev and his colleagues described these events in the Journal of Thrombosis and Haemostasis.

The team noted that platelets have many activators, but the chief among them are collagen, ADP, and thrombin.

Platelets detect different concentrations of an activator and respond with a varying frequency of calcium impulses in the cytoplasm.

The platelets’ mitochondria absorb and store the calcium, and when its concentration exceeds the critical level, the process of mitochondrial necrosis starts.

Calcium and reactive oxygen species are released from mitochondria, ATPases begin to destroy ATP instead of synthesizing it, the cell cytoskeleton collapses, and the platelets greatly increase in size.

As a result, at the outer membrane of the enlarged platelets, a lipid called phosphatidylserine appears, which is responsible for rapid blood clotting. And all this happens in seconds.

Thymectomy improved 3-year clinical outcomes and proved superior to medical therapy for mild to severe nonthymomatous myasthenia gravis, according to a report published online Aug. 11 in the New England Journal of Medicine.

Compared with standard prednisone therapy, thymectomy plus prednisone decreased the number and severity of symptoms, allowed the lowering of steroid doses, decreased the number and length of hospitalizations for disease exacerbations, reduced the need for immunosuppressive agents, and improved health-related quality of life in an international, randomized clinical trial, said Gil I. Wolfe, MD, of the department of neurology, State University of New York at Buffalo and his associates.

Until now, thymectomy was known to be beneficial in some cases of myasthenia gravis “but with widely varying rates of clinical improvement or remission.” And the success of immunotherapy has raised the question of whether an invasive surgery is necessary. Data from randomized, controlled studies have been sparse.

Moreover, thymectomy rarely causes adverse effects, but “the procedure can cost up to $80,000 and can be associated with operative complications that need to be weighed against benefits.” In comparison, medical therapy with glucocorticoids and other immunosuppressive agents is less invasive but is definitely associated with adverse events, including some that are life threatening, and negatively impacts quality of life, the investigators said.

To address the lack of randomized controlled trial data, they assessed 3-year outcomes in 126 patients treated at 67 medical centers in 18 countries during a 6-year period. The study participants were aged 18-65 years, had a disease duration of less than 5 years at enrollment (median duration, 1 year), and had class II (mild generalized disease) to class IV (severe generalized disease) myasthenia gravis. These patients were randomly assigned to undergo thymectomy and receive standard prednisone therapy (66 participants) or to receive standard prednisone alone (60 participants).

Thymectomy was performed using a median sternotomy “with the goal of an en bloc resection of all mediastinal tissue that could anatomically contain gross or microscopic thymus.”

At follow-up, time-weighted average scores on the Quantitative Myasthenia Gravis scale were significantly lower by 2.85 points, indicating improved clinical status, in the thymectomy group than in the control group. Time-weighted average prednisone dose also was significantly lower, at an average alternate-day dose of 44 mg in the thymectomy group and 60 mg in the control group, Dr. Wolfe and his associates said (N Engl J Med. 2016 Aug 11. doi: 10.1056/NEJMoa1602489).

On a measure of treatment-related complications, scores favored thymectomy with regard to the number of patients with symptoms, the total number of symptoms, and the distress level related to symptoms throughout the study period. Fewer patients in the thymectomy group required hospitalization for exacerbations of myasthenia gravis (9% vs. 37%), and the mean cumulative number of hospital days was lower with thymectomy (8.4 vs. 19.2).

In addition, scores on the Myasthenia Gravis Activities of Daily Living scale favored thymectomy (2.24 vs. 3.41). Fewer patients in the thymectomy group required azathioprine (17% vs. 0.48%). And the percentage of patients who reported having minimal manifestations of the disease at 3 years was significantly higher with thymectomy (67%) than with prednisone alone (47%).

This study was supported by the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association, and the Myasthenia Gravis Foundation of America and received no commercial support. Dr. Wolfe reported ties to Alexion Pharmaceuticals, Alpha Cancer Technologies, Argenx, Baxalta, CSL Behring, Grifols, and UCB, and his associates reported ties to numerous industry sources.

Thymectomy improved 3-year clinical outcomes and proved superior to medical therapy for mild to severe nonthymomatous myasthenia gravis, according to a report published online Aug. 11 in the New England Journal of Medicine.

Compared with standard prednisone therapy, thymectomy plus prednisone decreased the number and severity of symptoms, allowed the lowering of steroid doses, decreased the number and length of hospitalizations for disease exacerbations, reduced the need for immunosuppressive agents, and improved health-related quality of life in an international, randomized clinical trial, said Gil I. Wolfe, MD, of the department of neurology, State University of New York at Buffalo and his associates.

Until now, thymectomy was known to be beneficial in some cases of myasthenia gravis “but with widely varying rates of clinical improvement or remission.” And the success of immunotherapy has raised the question of whether an invasive surgery is necessary. Data from randomized, controlled studies have been sparse.

Moreover, thymectomy rarely causes adverse effects, but “the procedure can cost up to $80,000 and can be associated with operative complications that need to be weighed against benefits.” In comparison, medical therapy with glucocorticoids and other immunosuppressive agents is less invasive but is definitely associated with adverse events, including some that are life threatening, and negatively impacts quality of life, the investigators said.

To address the lack of randomized controlled trial data, they assessed 3-year outcomes in 126 patients treated at 67 medical centers in 18 countries during a 6-year period. The study participants were aged 18-65 years, had a disease duration of less than 5 years at enrollment (median duration, 1 year), and had class II (mild generalized disease) to class IV (severe generalized disease) myasthenia gravis. These patients were randomly assigned to undergo thymectomy and receive standard prednisone therapy (66 participants) or to receive standard prednisone alone (60 participants).

Thymectomy was performed using a median sternotomy “with the goal of an en bloc resection of all mediastinal tissue that could anatomically contain gross or microscopic thymus.”

At follow-up, time-weighted average scores on the Quantitative Myasthenia Gravis scale were significantly lower by 2.85 points, indicating improved clinical status, in the thymectomy group than in the control group. Time-weighted average prednisone dose also was significantly lower, at an average alternate-day dose of 44 mg in the thymectomy group and 60 mg in the control group, Dr. Wolfe and his associates said (N Engl J Med. 2016 Aug 11. doi: 10.1056/NEJMoa1602489).

On a measure of treatment-related complications, scores favored thymectomy with regard to the number of patients with symptoms, the total number of symptoms, and the distress level related to symptoms throughout the study period. Fewer patients in the thymectomy group required hospitalization for exacerbations of myasthenia gravis (9% vs. 37%), and the mean cumulative number of hospital days was lower with thymectomy (8.4 vs. 19.2).

In addition, scores on the Myasthenia Gravis Activities of Daily Living scale favored thymectomy (2.24 vs. 3.41). Fewer patients in the thymectomy group required azathioprine (17% vs. 0.48%). And the percentage of patients who reported having minimal manifestations of the disease at 3 years was significantly higher with thymectomy (67%) than with prednisone alone (47%).

This study was supported by the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association, and the Myasthenia Gravis Foundation of America and received no commercial support. Dr. Wolfe reported ties to Alexion Pharmaceuticals, Alpha Cancer Technologies, Argenx, Baxalta, CSL Behring, Grifols, and UCB, and his associates reported ties to numerous industry sources.

Thymectomy improved 3-year clinical outcomes and proved superior to medical therapy for mild to severe nonthymomatous myasthenia gravis, according to a report published online Aug. 11 in the New England Journal of Medicine.

Compared with standard prednisone therapy, thymectomy plus prednisone decreased the number and severity of symptoms, allowed the lowering of steroid doses, decreased the number and length of hospitalizations for disease exacerbations, reduced the need for immunosuppressive agents, and improved health-related quality of life in an international, randomized clinical trial, said Gil I. Wolfe, MD, of the department of neurology, State University of New York at Buffalo and his associates.

Until now, thymectomy was known to be beneficial in some cases of myasthenia gravis “but with widely varying rates of clinical improvement or remission.” And the success of immunotherapy has raised the question of whether an invasive surgery is necessary. Data from randomized, controlled studies have been sparse.

Moreover, thymectomy rarely causes adverse effects, but “the procedure can cost up to $80,000 and can be associated with operative complications that need to be weighed against benefits.” In comparison, medical therapy with glucocorticoids and other immunosuppressive agents is less invasive but is definitely associated with adverse events, including some that are life threatening, and negatively impacts quality of life, the investigators said.

To address the lack of randomized controlled trial data, they assessed 3-year outcomes in 126 patients treated at 67 medical centers in 18 countries during a 6-year period. The study participants were aged 18-65 years, had a disease duration of less than 5 years at enrollment (median duration, 1 year), and had class II (mild generalized disease) to class IV (severe generalized disease) myasthenia gravis. These patients were randomly assigned to undergo thymectomy and receive standard prednisone therapy (66 participants) or to receive standard prednisone alone (60 participants).

Thymectomy was performed using a median sternotomy “with the goal of an en bloc resection of all mediastinal tissue that could anatomically contain gross or microscopic thymus.”

At follow-up, time-weighted average scores on the Quantitative Myasthenia Gravis scale were significantly lower by 2.85 points, indicating improved clinical status, in the thymectomy group than in the control group. Time-weighted average prednisone dose also was significantly lower, at an average alternate-day dose of 44 mg in the thymectomy group and 60 mg in the control group, Dr. Wolfe and his associates said (N Engl J Med. 2016 Aug 11. doi: 10.1056/NEJMoa1602489).

On a measure of treatment-related complications, scores favored thymectomy with regard to the number of patients with symptoms, the total number of symptoms, and the distress level related to symptoms throughout the study period. Fewer patients in the thymectomy group required hospitalization for exacerbations of myasthenia gravis (9% vs. 37%), and the mean cumulative number of hospital days was lower with thymectomy (8.4 vs. 19.2).

In addition, scores on the Myasthenia Gravis Activities of Daily Living scale favored thymectomy (2.24 vs. 3.41). Fewer patients in the thymectomy group required azathioprine (17% vs. 0.48%). And the percentage of patients who reported having minimal manifestations of the disease at 3 years was significantly higher with thymectomy (67%) than with prednisone alone (47%).

This study was supported by the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association, and the Myasthenia Gravis Foundation of America and received no commercial support. Dr. Wolfe reported ties to Alexion Pharmaceuticals, Alpha Cancer Technologies, Argenx, Baxalta, CSL Behring, Grifols, and UCB, and his associates reported ties to numerous industry sources.

What does your patient need to know at the first visit?

In my practice, we try our best to start the education process before the patient even comes in for the first visit. If a patient is going to have a filler injection, we mail out an information packet that contains information on what to expect, how to minimize bruising, what side effects (eg, bruising, swelling) may occur, and what to avoid posttreatment. By providing them with this information prior to their visit, they can better plan their treatment around social and work obligations.

We ask patients to avoid or minimize blood-thinning agents such as aspirin, ibuprofen, fish oil, or vitamin E starting 2 weeks prior to and 1 week after the procedure. We recommend that patients take a pineapple extract such as bromelain 500 mg twice daily on an empty stomach starting 1 week prior to the treatment and for up to 1 week posttreatment. We ask that patients avoid exercise for 24 hours to reduce late-onset bruising and to avoid dental work for 2 weeks posttreatment to reduce the risk for the filler becoming infected.

What are your go-to treatments?

I use a variety of fillers depending on the area I am treating (thin vs thick skin) or the amount of lift I need (ie, G')(Restylane [Galderma Laboratories, LP] has a high G', thus it gives a lot of lift) versus the amount of water absorption I am seeking to further plump an area after the filler integrates (Juvéderm [Allergan] can absorb up to 300% its weight in water) versus the filler’s cohesiveness (Belotero [Merz Aesthetics] is highly cohesive). If I am treating a thin-faced individual, I may start with a global volumizer such as poly-L-lactic acid to get a good foundation set in the temples, cheeks, and jawline, and then after a few months, I will add a hyaluronic acid filler to focal areas that still need to be lifted (eg, nasolabial folds, tear troughs).

What are the side effects?

Side effects are divided into common and rare. Common would be bruising and swelling, which are temporary and will go away in all patients. Rare but serious side effects are infection and embolization. Both can cause notable tissue loss and risk to the patient. Every practitioner needs to know how to recognize and treat these complications should they arise.

How do you keep patients compliant?

Patients who get good results will always return, which means being up front about how much filler a patient needs and how frequently he/she will need it, and also doing everything we can to reduce bruising and swelling.


Suggested Readings

• Dayan SH, Arkins JP, Brindise R. Soft tissue fillers and biofilms. Facial Plast Surg. 2011;27:23-28.
• Orsini RA; Plastic Surgery Educational Technology Assessment Committee. Bromelain. Plast Reconstr Surg. 2006;118:1640-1644.

What does your patient need to know at the first visit?

In my practice, we try our best to start the education process before the patient even comes in for the first visit. If a patient is going to have a filler injection, we mail out an information packet that contains information on what to expect, how to minimize bruising, what side effects (eg, bruising, swelling) may occur, and what to avoid posttreatment. By providing them with this information prior to their visit, they can better plan their treatment around social and work obligations.

We ask patients to avoid or minimize blood-thinning agents such as aspirin, ibuprofen, fish oil, or vitamin E starting 2 weeks prior to and 1 week after the procedure. We recommend that patients take a pineapple extract such as bromelain 500 mg twice daily on an empty stomach starting 1 week prior to the treatment and for up to 1 week posttreatment. We ask that patients avoid exercise for 24 hours to reduce late-onset bruising and to avoid dental work for 2 weeks posttreatment to reduce the risk for the filler becoming infected.

What are your go-to treatments?

I use a variety of fillers depending on the area I am treating (thin vs thick skin) or the amount of lift I need (ie, G')(Restylane [Galderma Laboratories, LP] has a high G', thus it gives a lot of lift) versus the amount of water absorption I am seeking to further plump an area after the filler integrates (Juvéderm [Allergan] can absorb up to 300% its weight in water) versus the filler’s cohesiveness (Belotero [Merz Aesthetics] is highly cohesive). If I am treating a thin-faced individual, I may start with a global volumizer such as poly-L-lactic acid to get a good foundation set in the temples, cheeks, and jawline, and then after a few months, I will add a hyaluronic acid filler to focal areas that still need to be lifted (eg, nasolabial folds, tear troughs).

What are the side effects?

Side effects are divided into common and rare. Common would be bruising and swelling, which are temporary and will go away in all patients. Rare but serious side effects are infection and embolization. Both can cause notable tissue loss and risk to the patient. Every practitioner needs to know how to recognize and treat these complications should they arise.

How do you keep patients compliant?

Patients who get good results will always return, which means being up front about how much filler a patient needs and how frequently he/she will need it, and also doing everything we can to reduce bruising and swelling.


Suggested Readings

• Dayan SH, Arkins JP, Brindise R. Soft tissue fillers and biofilms. Facial Plast Surg. 2011;27:23-28.
• Orsini RA; Plastic Surgery Educational Technology Assessment Committee. Bromelain. Plast Reconstr Surg. 2006;118:1640-1644.

What does your patient need to know at the first visit?

In my practice, we try our best to start the education process before the patient even comes in for the first visit. If a patient is going to have a filler injection, we mail out an information packet that contains information on what to expect, how to minimize bruising, what side effects (eg, bruising, swelling) may occur, and what to avoid posttreatment. By providing them with this information prior to their visit, they can better plan their treatment around social and work obligations.

We ask patients to avoid or minimize blood-thinning agents such as aspirin, ibuprofen, fish oil, or vitamin E starting 2 weeks prior to and 1 week after the procedure. We recommend that patients take a pineapple extract such as bromelain 500 mg twice daily on an empty stomach starting 1 week prior to the treatment and for up to 1 week posttreatment. We ask that patients avoid exercise for 24 hours to reduce late-onset bruising and to avoid dental work for 2 weeks posttreatment to reduce the risk for the filler becoming infected.

What are your go-to treatments?

I use a variety of fillers depending on the area I am treating (thin vs thick skin) or the amount of lift I need (ie, G')(Restylane [Galderma Laboratories, LP] has a high G', thus it gives a lot of lift) versus the amount of water absorption I am seeking to further plump an area after the filler integrates (Juvéderm [Allergan] can absorb up to 300% its weight in water) versus the filler’s cohesiveness (Belotero [Merz Aesthetics] is highly cohesive). If I am treating a thin-faced individual, I may start with a global volumizer such as poly-L-lactic acid to get a good foundation set in the temples, cheeks, and jawline, and then after a few months, I will add a hyaluronic acid filler to focal areas that still need to be lifted (eg, nasolabial folds, tear troughs).

What are the side effects?

Side effects are divided into common and rare. Common would be bruising and swelling, which are temporary and will go away in all patients. Rare but serious side effects are infection and embolization. Both can cause notable tissue loss and risk to the patient. Every practitioner needs to know how to recognize and treat these complications should they arise.

How do you keep patients compliant?

Patients who get good results will always return, which means being up front about how much filler a patient needs and how frequently he/she will need it, and also doing everything we can to reduce bruising and swelling.


Suggested Readings

• Dayan SH, Arkins JP, Brindise R. Soft tissue fillers and biofilms. Facial Plast Surg. 2011;27:23-28.
• Orsini RA; Plastic Surgery Educational Technology Assessment Committee. Bromelain. Plast Reconstr Surg. 2006;118:1640-1644.

The incidence of Kaposi’s sarcoma among HIV patients has declined in the antiretroviral era, but the cancers are now presenting in older patients, after treatment starts, and in patients who have undetectable levels of HIV RNA.

Changes were also seen in the appearance of non-Hodgkin lymphoma, which is now occurring in patients with higher CD4 counts and lower HIV viral loads.

Although the findings of this large database study were largely driven by the fact that more patients are on antiretroviral therapy (ART) and in active clinical care, biological forces may also be at work, wrote Elizabeth L. Yanik, PhD, of the National Cancer Institute, Rockville, Md., and her associates (Am J Clin Oncol. 2016 Aug 9. doi: 10.1200/JCO.2016.67.6999).

“For example, cancers that develop in patients with HIV infection after immune recovery may manifest genetic or epigenetic changes that facilitate evasion from the immune system … [and] given that human herpesvirus-8 and Epstein-Barr virus are genetically heterogeneous, another possibility is that patients in whom Kaposi’s or non-Hodgkin lymphoma develops after immune reconstitution may be infected with more pathogenic strains.”

Dr. Yanik and her colleagues mined data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). The 24,901 patients have been followed from 1996-2011. Among them, 446 cases of Kaposi’s sarcoma (KS) and 258 cases of non-Hodgkin lymphoma (NHL) developed. Overall, KS and NHL incidence rates decreased 5% and 8% per year, respectively.

The proportion of KS diagnosed during routine care increased significantly, from 32% to 49%, reflecting the fact that more HIV patients continue to enter active clinical settings. The diagnostic setting of NHL did not change significantly over the study period, with 64% of cases being diagnosed in routine care in the latter years. From the beginning to the end of the study period, patient median age at diagnosis increased for both KS (from 37 to 42 years) and NHL (from 40 to 46 years).

The authors said this is a direct result of changing care patterns. “The proportion of KS cases diagnosed among patients who received ART increased not because KS incidence increased in patients who received ART but because of the growing fraction of the HIV population administered ART.”

As the study period progressed, more cases of KS appeared 6 months or longer after ART initiation, from 26% in the early years to 60% in the latter years. This change didn’t occur with NHL cases; 68% of them were diagnosed at least 6 months after ART began.

The mean CD4 count at diagnosis increased with time for both KS and NHL. During 2007-2011, 15% of KS cases and 24% of NHL cases were diagnosed at CD4 counts of 500 cells/mL or more, whereas less than half were diagnosed at CD4 counts less than 200 cells/mL, the authors observed.

Both cancers began to appear during periods of decreased viral load as the study progressed, although the decrease was only significant for NHL. However, from 2007 to 2011, 29% of KS cases and 51% of NHL cases were diagnosed when HIV RNA was suppressed to 500 copies/mL or lower.

Again, the authors related this to improved clinical care. “These clinical characteristics and the changes in the underlying HIV population are inherently related. Improvements in ART access and earlier initiation lead to earlier suppression of HIV RNA and, ultimately, higher CD4 counts,” they said.

[email protected]

On Twitter @Alz_Gal

The incidence of Kaposi’s sarcoma among HIV patients has declined in the antiretroviral era, but the cancers are now presenting in older patients, after treatment starts, and in patients who have undetectable levels of HIV RNA.

Changes were also seen in the appearance of non-Hodgkin lymphoma, which is now occurring in patients with higher CD4 counts and lower HIV viral loads.

Although the findings of this large database study were largely driven by the fact that more patients are on antiretroviral therapy (ART) and in active clinical care, biological forces may also be at work, wrote Elizabeth L. Yanik, PhD, of the National Cancer Institute, Rockville, Md., and her associates (Am J Clin Oncol. 2016 Aug 9. doi: 10.1200/JCO.2016.67.6999).

“For example, cancers that develop in patients with HIV infection after immune recovery may manifest genetic or epigenetic changes that facilitate evasion from the immune system … [and] given that human herpesvirus-8 and Epstein-Barr virus are genetically heterogeneous, another possibility is that patients in whom Kaposi’s or non-Hodgkin lymphoma develops after immune reconstitution may be infected with more pathogenic strains.”

Dr. Yanik and her colleagues mined data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). The 24,901 patients have been followed from 1996-2011. Among them, 446 cases of Kaposi’s sarcoma (KS) and 258 cases of non-Hodgkin lymphoma (NHL) developed. Overall, KS and NHL incidence rates decreased 5% and 8% per year, respectively.

The proportion of KS diagnosed during routine care increased significantly, from 32% to 49%, reflecting the fact that more HIV patients continue to enter active clinical settings. The diagnostic setting of NHL did not change significantly over the study period, with 64% of cases being diagnosed in routine care in the latter years. From the beginning to the end of the study period, patient median age at diagnosis increased for both KS (from 37 to 42 years) and NHL (from 40 to 46 years).

The authors said this is a direct result of changing care patterns. “The proportion of KS cases diagnosed among patients who received ART increased not because KS incidence increased in patients who received ART but because of the growing fraction of the HIV population administered ART.”

As the study period progressed, more cases of KS appeared 6 months or longer after ART initiation, from 26% in the early years to 60% in the latter years. This change didn’t occur with NHL cases; 68% of them were diagnosed at least 6 months after ART began.

The mean CD4 count at diagnosis increased with time for both KS and NHL. During 2007-2011, 15% of KS cases and 24% of NHL cases were diagnosed at CD4 counts of 500 cells/mL or more, whereas less than half were diagnosed at CD4 counts less than 200 cells/mL, the authors observed.

Both cancers began to appear during periods of decreased viral load as the study progressed, although the decrease was only significant for NHL. However, from 2007 to 2011, 29% of KS cases and 51% of NHL cases were diagnosed when HIV RNA was suppressed to 500 copies/mL or lower.

Again, the authors related this to improved clinical care. “These clinical characteristics and the changes in the underlying HIV population are inherently related. Improvements in ART access and earlier initiation lead to earlier suppression of HIV RNA and, ultimately, higher CD4 counts,” they said.

[email protected]

On Twitter @Alz_Gal

The incidence of Kaposi’s sarcoma among HIV patients has declined in the antiretroviral era, but the cancers are now presenting in older patients, after treatment starts, and in patients who have undetectable levels of HIV RNA.

Changes were also seen in the appearance of non-Hodgkin lymphoma, which is now occurring in patients with higher CD4 counts and lower HIV viral loads.

Although the findings of this large database study were largely driven by the fact that more patients are on antiretroviral therapy (ART) and in active clinical care, biological forces may also be at work, wrote Elizabeth L. Yanik, PhD, of the National Cancer Institute, Rockville, Md., and her associates (Am J Clin Oncol. 2016 Aug 9. doi: 10.1200/JCO.2016.67.6999).

“For example, cancers that develop in patients with HIV infection after immune recovery may manifest genetic or epigenetic changes that facilitate evasion from the immune system … [and] given that human herpesvirus-8 and Epstein-Barr virus are genetically heterogeneous, another possibility is that patients in whom Kaposi’s or non-Hodgkin lymphoma develops after immune reconstitution may be infected with more pathogenic strains.”

Dr. Yanik and her colleagues mined data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). The 24,901 patients have been followed from 1996-2011. Among them, 446 cases of Kaposi’s sarcoma (KS) and 258 cases of non-Hodgkin lymphoma (NHL) developed. Overall, KS and NHL incidence rates decreased 5% and 8% per year, respectively.

The proportion of KS diagnosed during routine care increased significantly, from 32% to 49%, reflecting the fact that more HIV patients continue to enter active clinical settings. The diagnostic setting of NHL did not change significantly over the study period, with 64% of cases being diagnosed in routine care in the latter years. From the beginning to the end of the study period, patient median age at diagnosis increased for both KS (from 37 to 42 years) and NHL (from 40 to 46 years).

The authors said this is a direct result of changing care patterns. “The proportion of KS cases diagnosed among patients who received ART increased not because KS incidence increased in patients who received ART but because of the growing fraction of the HIV population administered ART.”

As the study period progressed, more cases of KS appeared 6 months or longer after ART initiation, from 26% in the early years to 60% in the latter years. This change didn’t occur with NHL cases; 68% of them were diagnosed at least 6 months after ART began.

The mean CD4 count at diagnosis increased with time for both KS and NHL. During 2007-2011, 15% of KS cases and 24% of NHL cases were diagnosed at CD4 counts of 500 cells/mL or more, whereas less than half were diagnosed at CD4 counts less than 200 cells/mL, the authors observed.

Both cancers began to appear during periods of decreased viral load as the study progressed, although the decrease was only significant for NHL. However, from 2007 to 2011, 29% of KS cases and 51% of NHL cases were diagnosed when HIV RNA was suppressed to 500 copies/mL or lower.

Again, the authors related this to improved clinical care. “These clinical characteristics and the changes in the underlying HIV population are inherently related. Improvements in ART access and earlier initiation lead to earlier suppression of HIV RNA and, ultimately, higher CD4 counts,” they said.

[email protected]

On Twitter @Alz_Gal

Testing for West Nile virus (WNV) is underutilized in areas where the disease is endemic, according to Jakapat Vanichanan, MD, and his associates.

In a sample of 751 patients admitted to Houston hospitals for meningitis or encephalitis, 390 patients experienced onset of symptoms during the WNV peak season between June and October, but only 281 of the 751 patients received WNV testing. Of the 281 patients tested for WNV, 32 were diagnosed with acute infection.

jarun011/Thinkstock

Patients tested for WNV were more likely to have acute focal neurologic deficits, be of older age, require an MRI, be prescribed antiviral therapy, have worse clinical outcomes, and experience concomitant testing for mycobacterial, fungal, or other viral infections. Of the 32 patients diagnosed with WNV, 16 were admitted with meningitis and 16 were admitted with encephalitis.

“Although supportive treatment remains the standard of care for patients with WNND [West Nile neuroinvasive diseases], performing appropriate WNV testing may yield several benefits. An accurate diagnosis more precisely defines disease burden and epidemiology, an ongoing surveillance deficiency. Moreover, identifying WNV may lead to early detection of long-term neurologic and neurocognitive sequelae after WNND and thus enable earlier intervention,” the investigators said.

Find the full study in Emerging Infectious Diseases (doi: 10.3201/eid2209.152050).

[email protected]

Testing for West Nile virus (WNV) is underutilized in areas where the disease is endemic, according to Jakapat Vanichanan, MD, and his associates.

In a sample of 751 patients admitted to Houston hospitals for meningitis or encephalitis, 390 patients experienced onset of symptoms during the WNV peak season between June and October, but only 281 of the 751 patients received WNV testing. Of the 281 patients tested for WNV, 32 were diagnosed with acute infection.

jarun011/Thinkstock

Patients tested for WNV were more likely to have acute focal neurologic deficits, be of older age, require an MRI, be prescribed antiviral therapy, have worse clinical outcomes, and experience concomitant testing for mycobacterial, fungal, or other viral infections. Of the 32 patients diagnosed with WNV, 16 were admitted with meningitis and 16 were admitted with encephalitis.

“Although supportive treatment remains the standard of care for patients with WNND [West Nile neuroinvasive diseases], performing appropriate WNV testing may yield several benefits. An accurate diagnosis more precisely defines disease burden and epidemiology, an ongoing surveillance deficiency. Moreover, identifying WNV may lead to early detection of long-term neurologic and neurocognitive sequelae after WNND and thus enable earlier intervention,” the investigators said.

Find the full study in Emerging Infectious Diseases (doi: 10.3201/eid2209.152050).

[email protected]

Testing for West Nile virus (WNV) is underutilized in areas where the disease is endemic, according to Jakapat Vanichanan, MD, and his associates.

In a sample of 751 patients admitted to Houston hospitals for meningitis or encephalitis, 390 patients experienced onset of symptoms during the WNV peak season between June and October, but only 281 of the 751 patients received WNV testing. Of the 281 patients tested for WNV, 32 were diagnosed with acute infection.

jarun011/Thinkstock

Patients tested for WNV were more likely to have acute focal neurologic deficits, be of older age, require an MRI, be prescribed antiviral therapy, have worse clinical outcomes, and experience concomitant testing for mycobacterial, fungal, or other viral infections. Of the 32 patients diagnosed with WNV, 16 were admitted with meningitis and 16 were admitted with encephalitis.

“Although supportive treatment remains the standard of care for patients with WNND [West Nile neuroinvasive diseases], performing appropriate WNV testing may yield several benefits. An accurate diagnosis more precisely defines disease burden and epidemiology, an ongoing surveillance deficiency. Moreover, identifying WNV may lead to early detection of long-term neurologic and neurocognitive sequelae after WNND and thus enable earlier intervention,” the investigators said.

Find the full study in Emerging Infectious Diseases (doi: 10.3201/eid2209.152050).

[email protected]

Fibrosis progression in hepatitis C virus–infected individuals is not linear, is associated with Clues to fibrosis progression in chronic hepatitis C infectionClues to fibrosis progression in chronic hepatitis C infection–related flares, and varies according to stage, with those who are least fibrotic tending to have the highest progression, according to a study.

Identifying which patients with hepatitis C virus (HCV) infection will likely progress to cirrhosis has historically been a challenge, creating some difficulty adhering to guidelines recommending that patients at greater risk of fibrosis be among those prioritized for treatment. Having an ability to more accurately diagnose those most at risk could help to better guide treatment prioritization and clinical management.

To that end, Marija Zeremski, PhD, and her colleagues at Weill Cornell Medical School, New York, analyzed 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013. At the time of the first biopsy, nearly two-thirds of the patients were white men in their late 40s to mid-50s, with chronic HCV infection. Nearly 88% of all patients were HCV genotype 1 infected (J Infect Dis. 2016. doi: 10.1093/infdis/jiw332).

In the study, investigators found that between the first and a follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis. Fibrosis progression between the first and last biopsies was associated with less fibrosis on the first biopsy (P less than .001).

Increased necroinflammation and the presence of at least one alanine aminotransferase (ALT) flare greater than 200 U/L during follow-up was also significantly associated with fibrosis progression (odds ratio [OR], 2.64, P less than .007). HCV genotype 3–infected patients were significantly more likely to progress to cirrhosis (P less than .001).

Intrahepatic inflammation at the time of the initial biopsy was at grade 1 or lower in 36.4% of patients, while 56.9% of patients had grade 2 (moderate) inflammation. Severe inflammation (grade 3 or higher) was found in 6.7% of patients reviewed. There was no fibrosis in 11.9% of patients, stage 1 level of fibrosis in 32.3%, stage 2 in 39.4%, and stage 3 in 16.4% of patients.

Moderate to severe fibrosis, defined as equal to or greater than stage 2, was significantly associated with elevated inflammation (greater or equal to grade 2) on the initial biopsy (OR, 9.00; P less than .001). Steatosis testing was performed on 222 patients; 59% tested positive for it. This was significantly associated with stage 2 or higher fibrosis (OR, 2.39; P = .002), and grade 2 or higher levels of inflammation (OR, 4.07; P less than .001) on the initial biopsy.

The highest fibrosis progression rate occurred between stages 0 and 1; the lowest, between stages 2 and 3.

Consecutive biopsies were separated by at least 1 year; patients were either HCV treatment naive or were treatment nonresponders. There were a total of 558 consecutive biopsy pairs available to analyze stage progression. The time between the first and last biopsies was 6.5 years (plus or minus 3 years), while the mean duration between adjacent biopsies was 4.4 years (plus or minus 1.9 years). Data regarding HCV treatment between liver biopsies were available for all but 45 patients. Forty-three percent of the remaining patients did not achieve a sustained virologic response after treatment.

Patients who’d had a cirrhosis diagnosis according to the first biopsy, those for whom treatment induced viral eradication, or those who’d had liver transplantation between biopsies were all excluded from the review.

The investigators wrote that their finding about the association between genotype 3 and cirrhosis should be “interpreted cautiously” because of the low number of these patients in their study.

This article was updated August 17, 2016.

[email protected]

On Twitter @whitneymcknight

Fibrosis progression in hepatitis C virus–infected individuals is not linear, is associated with Clues to fibrosis progression in chronic hepatitis C infectionClues to fibrosis progression in chronic hepatitis C infection–related flares, and varies according to stage, with those who are least fibrotic tending to have the highest progression, according to a study.

Identifying which patients with hepatitis C virus (HCV) infection will likely progress to cirrhosis has historically been a challenge, creating some difficulty adhering to guidelines recommending that patients at greater risk of fibrosis be among those prioritized for treatment. Having an ability to more accurately diagnose those most at risk could help to better guide treatment prioritization and clinical management.

To that end, Marija Zeremski, PhD, and her colleagues at Weill Cornell Medical School, New York, analyzed 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013. At the time of the first biopsy, nearly two-thirds of the patients were white men in their late 40s to mid-50s, with chronic HCV infection. Nearly 88% of all patients were HCV genotype 1 infected (J Infect Dis. 2016. doi: 10.1093/infdis/jiw332).

In the study, investigators found that between the first and a follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis. Fibrosis progression between the first and last biopsies was associated with less fibrosis on the first biopsy (P less than .001).

Increased necroinflammation and the presence of at least one alanine aminotransferase (ALT) flare greater than 200 U/L during follow-up was also significantly associated with fibrosis progression (odds ratio [OR], 2.64, P less than .007). HCV genotype 3–infected patients were significantly more likely to progress to cirrhosis (P less than .001).

Intrahepatic inflammation at the time of the initial biopsy was at grade 1 or lower in 36.4% of patients, while 56.9% of patients had grade 2 (moderate) inflammation. Severe inflammation (grade 3 or higher) was found in 6.7% of patients reviewed. There was no fibrosis in 11.9% of patients, stage 1 level of fibrosis in 32.3%, stage 2 in 39.4%, and stage 3 in 16.4% of patients.

Moderate to severe fibrosis, defined as equal to or greater than stage 2, was significantly associated with elevated inflammation (greater or equal to grade 2) on the initial biopsy (OR, 9.00; P less than .001). Steatosis testing was performed on 222 patients; 59% tested positive for it. This was significantly associated with stage 2 or higher fibrosis (OR, 2.39; P = .002), and grade 2 or higher levels of inflammation (OR, 4.07; P less than .001) on the initial biopsy.

The highest fibrosis progression rate occurred between stages 0 and 1; the lowest, between stages 2 and 3.

Consecutive biopsies were separated by at least 1 year; patients were either HCV treatment naive or were treatment nonresponders. There were a total of 558 consecutive biopsy pairs available to analyze stage progression. The time between the first and last biopsies was 6.5 years (plus or minus 3 years), while the mean duration between adjacent biopsies was 4.4 years (plus or minus 1.9 years). Data regarding HCV treatment between liver biopsies were available for all but 45 patients. Forty-three percent of the remaining patients did not achieve a sustained virologic response after treatment.

Patients who’d had a cirrhosis diagnosis according to the first biopsy, those for whom treatment induced viral eradication, or those who’d had liver transplantation between biopsies were all excluded from the review.

The investigators wrote that their finding about the association between genotype 3 and cirrhosis should be “interpreted cautiously” because of the low number of these patients in their study.

This article was updated August 17, 2016.

[email protected]

On Twitter @whitneymcknight

Fibrosis progression in hepatitis C virus–infected individuals is not linear, is associated with Clues to fibrosis progression in chronic hepatitis C infectionClues to fibrosis progression in chronic hepatitis C infection–related flares, and varies according to stage, with those who are least fibrotic tending to have the highest progression, according to a study.

Identifying which patients with hepatitis C virus (HCV) infection will likely progress to cirrhosis has historically been a challenge, creating some difficulty adhering to guidelines recommending that patients at greater risk of fibrosis be among those prioritized for treatment. Having an ability to more accurately diagnose those most at risk could help to better guide treatment prioritization and clinical management.

To that end, Marija Zeremski, PhD, and her colleagues at Weill Cornell Medical School, New York, analyzed 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013. At the time of the first biopsy, nearly two-thirds of the patients were white men in their late 40s to mid-50s, with chronic HCV infection. Nearly 88% of all patients were HCV genotype 1 infected (J Infect Dis. 2016. doi: 10.1093/infdis/jiw332).

In the study, investigators found that between the first and a follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis. Fibrosis progression between the first and last biopsies was associated with less fibrosis on the first biopsy (P less than .001).

Increased necroinflammation and the presence of at least one alanine aminotransferase (ALT) flare greater than 200 U/L during follow-up was also significantly associated with fibrosis progression (odds ratio [OR], 2.64, P less than .007). HCV genotype 3–infected patients were significantly more likely to progress to cirrhosis (P less than .001).

Intrahepatic inflammation at the time of the initial biopsy was at grade 1 or lower in 36.4% of patients, while 56.9% of patients had grade 2 (moderate) inflammation. Severe inflammation (grade 3 or higher) was found in 6.7% of patients reviewed. There was no fibrosis in 11.9% of patients, stage 1 level of fibrosis in 32.3%, stage 2 in 39.4%, and stage 3 in 16.4% of patients.

Moderate to severe fibrosis, defined as equal to or greater than stage 2, was significantly associated with elevated inflammation (greater or equal to grade 2) on the initial biopsy (OR, 9.00; P less than .001). Steatosis testing was performed on 222 patients; 59% tested positive for it. This was significantly associated with stage 2 or higher fibrosis (OR, 2.39; P = .002), and grade 2 or higher levels of inflammation (OR, 4.07; P less than .001) on the initial biopsy.

The highest fibrosis progression rate occurred between stages 0 and 1; the lowest, between stages 2 and 3.

Consecutive biopsies were separated by at least 1 year; patients were either HCV treatment naive or were treatment nonresponders. There were a total of 558 consecutive biopsy pairs available to analyze stage progression. The time between the first and last biopsies was 6.5 years (plus or minus 3 years), while the mean duration between adjacent biopsies was 4.4 years (plus or minus 1.9 years). Data regarding HCV treatment between liver biopsies were available for all but 45 patients. Forty-three percent of the remaining patients did not achieve a sustained virologic response after treatment.

Patients who’d had a cirrhosis diagnosis according to the first biopsy, those for whom treatment induced viral eradication, or those who’d had liver transplantation between biopsies were all excluded from the review.

The investigators wrote that their finding about the association between genotype 3 and cirrhosis should be “interpreted cautiously” because of the low number of these patients in their study.

This article was updated August 17, 2016.

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Survivors of fusion-negative sarcomas have a higher risk of developing second malignant neoplasms, report Philip J. Lupo, PhD, and his coauthors from the Baylor College of Medicine in Houston.

Investigators evaluated 4,822 survivors of fusion-positive (F+) sarcomas and 3,963 survivors of fusion-negative (F–) sarcomas aged birth-39 years. Patients were diagnosed between 1992 and 2012, and were included in the Surveillance, Epidemiology, and End Results (SEER) database.

Results showed that second malignancy risk was almost two times higher in F+ sarcoma patients, compared with the reference population (standardized incidence ratio = 1.86; 95% confidence interval, 1.48-2.30), and almost three times higher in survivors of F– sarcomas (SIR = 2.89; 95% CI, 2.30-3.59).

Second malignancy types were similar between F+ and F– survivors. However, the second malignant neoplasm rate was greater among survivors of F– sarcomas (adjusted hazard ratio = 1.38; 95% CI, 1.01-1.89) when compared with survivors of F+ sarcomas, Dr. Lupo and his colleagues reported.

Read the full study in Cancer.

Survivors of fusion-negative sarcomas have a higher risk of developing second malignant neoplasms, report Philip J. Lupo, PhD, and his coauthors from the Baylor College of Medicine in Houston.

Investigators evaluated 4,822 survivors of fusion-positive (F+) sarcomas and 3,963 survivors of fusion-negative (F–) sarcomas aged birth-39 years. Patients were diagnosed between 1992 and 2012, and were included in the Surveillance, Epidemiology, and End Results (SEER) database.

Results showed that second malignancy risk was almost two times higher in F+ sarcoma patients, compared with the reference population (standardized incidence ratio = 1.86; 95% confidence interval, 1.48-2.30), and almost three times higher in survivors of F– sarcomas (SIR = 2.89; 95% CI, 2.30-3.59).

Second malignancy types were similar between F+ and F– survivors. However, the second malignant neoplasm rate was greater among survivors of F– sarcomas (adjusted hazard ratio = 1.38; 95% CI, 1.01-1.89) when compared with survivors of F+ sarcomas, Dr. Lupo and his colleagues reported.

Read the full study in Cancer.

Survivors of fusion-negative sarcomas have a higher risk of developing second malignant neoplasms, report Philip J. Lupo, PhD, and his coauthors from the Baylor College of Medicine in Houston.

Investigators evaluated 4,822 survivors of fusion-positive (F+) sarcomas and 3,963 survivors of fusion-negative (F–) sarcomas aged birth-39 years. Patients were diagnosed between 1992 and 2012, and were included in the Surveillance, Epidemiology, and End Results (SEER) database.

Results showed that second malignancy risk was almost two times higher in F+ sarcoma patients, compared with the reference population (standardized incidence ratio = 1.86; 95% confidence interval, 1.48-2.30), and almost three times higher in survivors of F– sarcomas (SIR = 2.89; 95% CI, 2.30-3.59).

Second malignancy types were similar between F+ and F– survivors. However, the second malignant neoplasm rate was greater among survivors of F– sarcomas (adjusted hazard ratio = 1.38; 95% CI, 1.01-1.89) when compared with survivors of F+ sarcomas, Dr. Lupo and his colleagues reported.

Read the full study in Cancer.