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Localized wheezing differs from asthmatic, viral wheezing

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CHICAGO – Nearly half of all children have wheezing in their first year of life, and one in five have recurrent wheezing episodes, but that doesn’t mean they have asthma, explained Erik Hysinger, MD, MS, of the division of pulmonary medicine at Cincinnati Children’s Hospital.

Localized wheezing is not consistent with asthmatic or viral wheezing, which is typically diffuse and polyphonic, Dr. Hysinger emphasized at the annual meeting of the American Academy of Pediatrics.

“Localized wheezing is less common than diffuse wheezing and typically has a homophonous sound,” Dr. Hysinger said. It also usually arises from a central airway pathology. “High flow rates create loud amplitude sounds.”

iStock/Thinkstock
He discussed different presentations of localized wheezing and reviewed the three categories of differential diagnosis for nonasthmatic, nonviral wheezing: airway occlusion, airway narrowing, or airway compression.

Dr. Hysinger also covered management strategies for focal wheezing, starting with an initial trial of bronchodilators. Any wheezing resulting from a central airway problem, however, isn’t likely to respond to bronchodilators. Standard work-up for any of these causes is usually a chest x-ray, often paired with a bronchoscopy. Persistent wheezing likely needs a chest CT, and many of these conditions will require referral to a subspecialist.

Airway occlusion diagnoses

Four potential causes of an airway blockage are a foreign body, a bronchial cast, mucous plugs, or airway tumors.

A foreign body typically occurs with a cough, wheezing, stridor, and respiratory distress. It is most common in children under age 4 years, usually in those without a history of aspiration, yet providers initially misdiagnose more than 20% of patients with a foreign body. The foreign object – often coins, food, or batteries – frequently ends up in the right main bronchus and may go undetected up to a month, potentially leading to pneumonia, abscess, atelectasis, bronchiectasis, or airway erosion.

Dr. Erik Hysinger
The recommended initial evaluation, a bilateral decubitus chest x-ray, nevertheless cannot rule out a foreign body on its own because the objects may not show up on the films and only two-thirds of cases show an asymmetric hyperinflation. Physicians who suspect that a foreign body may be causing the wheeze should conduct a bronchoscopy. Obviously, the treatment is to remove the object, but providers also should expect to treat possible comorbidities if it took a while to identify and extract the object.

An endobronchial cast is rarer than a foreign body, but can be large enough to completely fill a lung with branching mucin, fibrin, and inflammatory cells. The wheezing sounds homophonous, with a barky or brassy cough accompanied by atelectasis. Dr. Hysinger recommended ordering chest x-ray, echocardiogram, and bronchoscopy. Although often idiopathic, these casts also can result from asthma or another disease: neutrophilic inflammation typically indicates a heart condition whereas asthma or influenza leads to eosinophilic inflammation.

Treatment should involve clearing the airway, followed by hypertonic saline, an inhaled tissue plasminogen activator, and a bronchoscopy for extraction.

Although distinct from endobronchial casts, a mucus plug also presents with wheezing, a cough, and atelectasis, and potentially respiratory distress or failure, and hypoxemia. Mucus plugs are diagnosed with a chest x-ray and flexible bronchoscopy, and then treated by removing the plug and clearing the airway, hypertonic saline, and mucolytics.

The rarest cause of an airway blockage is an airway tumor, often mistaken for asthma. Benign causes include papillomatosis, hemangioma, and hamartomas, while potentially malignant causes include a carcinoid, mucoepidermoid carcinoma, inflammatory myofibromas, and granular cell tumors.

In addition to a chest x-ray and bronchoscopy, a chest CT scan plus a biopsy and resection are necessary to diagnose airway tumors. Treatment will depend on the specific type of tumor identified.

“Overall survival is excellent,” Dr. Hysinger said of children with airway tumors.

Airway narrowing diagnoses

Two possible diagnoses for an intrinsic airway narrowing include bronchomalacia, occurring in only 1 of 2,100 children, and bronchial stenosis.

In bronchomalacia – diagnosed primarily with bronchoscopy – the airway collapses from weakening of the cartilage and posterior membrane. Bronchomalacia sounds like homophonous wheezing with a barky or brassy cough, and it’s frequently accompanied by recurrent bronchitis and/or pneumonia. Intervention is rarely necessary when occurring on its own, but severe cases may require endobronchial stents. Dr. Hysinger also recommended considering ipratroprium instead of albuterol.

Bronchial stenosis involves a fixed narrowing of the bronchi and can be congenital – typically occurring with heart disease – or acquired after an intubation and suction trauma or bronchiolitis obliterans (“popcorn lung”). A chest x-ray and bronchoscopy again are standard, but MRI may be necessary as well. Aside from helping the patient clear the airway, bronchial stenosis typically needs limited management unless the patient is symptomatic. In that case, options include balloon dilation, endobronchial stents, or a slide bronchoplasty.

 

 

Airway compression diagnoses

An extrinsic airway compression could have a vascular cause or could result from pressure by an extrinsic mass or the axial skeleton.

Vascular compression usually occurs due to abnormal vasculature development, particularly with vascular stents, Dr. Hysinger said. The wheezing presents with stridor, feeding intolerance, recurrent infections, and cyanotic episodes. The work-up should include a chest x-ray, bronchoscopy, and a chest CT and/or MRI. A variety of interventions may be necessary to treat it, including an aortopexy, pulmonary artery trunk–pexy, arterioplasty, vessel implantation, or endobronchial stent. Residual malacia may remain after treatment, however.

The most common reasons for airway compression by some kind of mass is a reactive lymphadenopathy, a tumor, or an infection, including tuberculosis or histoplasmosis. Severe narrowing of the airway can lead to respiratory failure, but because the compression can develop slowly, the wheezing can be mistaken for asthma. In addition to a chest CT and bronchoscopy, a patient will need other work-ups depending on the cause. Possibilities include a biopsy, a gastric aspirate (for tuberculosis), a bronchoalveolar lavage, or antibody titers.

Similarly, because therapeutic intervention requires treating the underlying infection, specific treatments will vary. Tumors typically will need resection, chemotherapy, and/or radiation – and, until the airway is fully cleared, the patient may need chronic mechanical ventilation.

Children with severe scoliosis or kyphosis are those most likely to experience airway compression resulting from pressure by the axial skeleton, in which the spine’s curvature directly presses on the airway. In addition to the wheeze, these patients may have respiratory distress or recurrent focal pneumonia, Dr. Hysinger said. The standard work-up involves a chest x-ray, chest CT, spinal MRI, and bronchoscopy.

Consider using spinal rods, but they can both help the condition or potentially exacerbate the compression, Dr. Hysinger said. Either way, children also will need help with airway clearance and coughing.

Dr. Hysinger concluded by reviewing what you may consider changing in your current practice, including the initial trial of bronchodilators, a chest x-ray, and a subspecialist referral.

No funding was used for this presentation, and Dr. Hysinger reported having no relevant financial disclosures.

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CHICAGO – Nearly half of all children have wheezing in their first year of life, and one in five have recurrent wheezing episodes, but that doesn’t mean they have asthma, explained Erik Hysinger, MD, MS, of the division of pulmonary medicine at Cincinnati Children’s Hospital.

Localized wheezing is not consistent with asthmatic or viral wheezing, which is typically diffuse and polyphonic, Dr. Hysinger emphasized at the annual meeting of the American Academy of Pediatrics.

“Localized wheezing is less common than diffuse wheezing and typically has a homophonous sound,” Dr. Hysinger said. It also usually arises from a central airway pathology. “High flow rates create loud amplitude sounds.”

iStock/Thinkstock
He discussed different presentations of localized wheezing and reviewed the three categories of differential diagnosis for nonasthmatic, nonviral wheezing: airway occlusion, airway narrowing, or airway compression.

Dr. Hysinger also covered management strategies for focal wheezing, starting with an initial trial of bronchodilators. Any wheezing resulting from a central airway problem, however, isn’t likely to respond to bronchodilators. Standard work-up for any of these causes is usually a chest x-ray, often paired with a bronchoscopy. Persistent wheezing likely needs a chest CT, and many of these conditions will require referral to a subspecialist.

Airway occlusion diagnoses

Four potential causes of an airway blockage are a foreign body, a bronchial cast, mucous plugs, or airway tumors.

A foreign body typically occurs with a cough, wheezing, stridor, and respiratory distress. It is most common in children under age 4 years, usually in those without a history of aspiration, yet providers initially misdiagnose more than 20% of patients with a foreign body. The foreign object – often coins, food, or batteries – frequently ends up in the right main bronchus and may go undetected up to a month, potentially leading to pneumonia, abscess, atelectasis, bronchiectasis, or airway erosion.

Dr. Erik Hysinger
The recommended initial evaluation, a bilateral decubitus chest x-ray, nevertheless cannot rule out a foreign body on its own because the objects may not show up on the films and only two-thirds of cases show an asymmetric hyperinflation. Physicians who suspect that a foreign body may be causing the wheeze should conduct a bronchoscopy. Obviously, the treatment is to remove the object, but providers also should expect to treat possible comorbidities if it took a while to identify and extract the object.

An endobronchial cast is rarer than a foreign body, but can be large enough to completely fill a lung with branching mucin, fibrin, and inflammatory cells. The wheezing sounds homophonous, with a barky or brassy cough accompanied by atelectasis. Dr. Hysinger recommended ordering chest x-ray, echocardiogram, and bronchoscopy. Although often idiopathic, these casts also can result from asthma or another disease: neutrophilic inflammation typically indicates a heart condition whereas asthma or influenza leads to eosinophilic inflammation.

Treatment should involve clearing the airway, followed by hypertonic saline, an inhaled tissue plasminogen activator, and a bronchoscopy for extraction.

Although distinct from endobronchial casts, a mucus plug also presents with wheezing, a cough, and atelectasis, and potentially respiratory distress or failure, and hypoxemia. Mucus plugs are diagnosed with a chest x-ray and flexible bronchoscopy, and then treated by removing the plug and clearing the airway, hypertonic saline, and mucolytics.

The rarest cause of an airway blockage is an airway tumor, often mistaken for asthma. Benign causes include papillomatosis, hemangioma, and hamartomas, while potentially malignant causes include a carcinoid, mucoepidermoid carcinoma, inflammatory myofibromas, and granular cell tumors.

In addition to a chest x-ray and bronchoscopy, a chest CT scan plus a biopsy and resection are necessary to diagnose airway tumors. Treatment will depend on the specific type of tumor identified.

“Overall survival is excellent,” Dr. Hysinger said of children with airway tumors.

Airway narrowing diagnoses

Two possible diagnoses for an intrinsic airway narrowing include bronchomalacia, occurring in only 1 of 2,100 children, and bronchial stenosis.

In bronchomalacia – diagnosed primarily with bronchoscopy – the airway collapses from weakening of the cartilage and posterior membrane. Bronchomalacia sounds like homophonous wheezing with a barky or brassy cough, and it’s frequently accompanied by recurrent bronchitis and/or pneumonia. Intervention is rarely necessary when occurring on its own, but severe cases may require endobronchial stents. Dr. Hysinger also recommended considering ipratroprium instead of albuterol.

Bronchial stenosis involves a fixed narrowing of the bronchi and can be congenital – typically occurring with heart disease – or acquired after an intubation and suction trauma or bronchiolitis obliterans (“popcorn lung”). A chest x-ray and bronchoscopy again are standard, but MRI may be necessary as well. Aside from helping the patient clear the airway, bronchial stenosis typically needs limited management unless the patient is symptomatic. In that case, options include balloon dilation, endobronchial stents, or a slide bronchoplasty.

 

 

Airway compression diagnoses

An extrinsic airway compression could have a vascular cause or could result from pressure by an extrinsic mass or the axial skeleton.

Vascular compression usually occurs due to abnormal vasculature development, particularly with vascular stents, Dr. Hysinger said. The wheezing presents with stridor, feeding intolerance, recurrent infections, and cyanotic episodes. The work-up should include a chest x-ray, bronchoscopy, and a chest CT and/or MRI. A variety of interventions may be necessary to treat it, including an aortopexy, pulmonary artery trunk–pexy, arterioplasty, vessel implantation, or endobronchial stent. Residual malacia may remain after treatment, however.

The most common reasons for airway compression by some kind of mass is a reactive lymphadenopathy, a tumor, or an infection, including tuberculosis or histoplasmosis. Severe narrowing of the airway can lead to respiratory failure, but because the compression can develop slowly, the wheezing can be mistaken for asthma. In addition to a chest CT and bronchoscopy, a patient will need other work-ups depending on the cause. Possibilities include a biopsy, a gastric aspirate (for tuberculosis), a bronchoalveolar lavage, or antibody titers.

Similarly, because therapeutic intervention requires treating the underlying infection, specific treatments will vary. Tumors typically will need resection, chemotherapy, and/or radiation – and, until the airway is fully cleared, the patient may need chronic mechanical ventilation.

Children with severe scoliosis or kyphosis are those most likely to experience airway compression resulting from pressure by the axial skeleton, in which the spine’s curvature directly presses on the airway. In addition to the wheeze, these patients may have respiratory distress or recurrent focal pneumonia, Dr. Hysinger said. The standard work-up involves a chest x-ray, chest CT, spinal MRI, and bronchoscopy.

Consider using spinal rods, but they can both help the condition or potentially exacerbate the compression, Dr. Hysinger said. Either way, children also will need help with airway clearance and coughing.

Dr. Hysinger concluded by reviewing what you may consider changing in your current practice, including the initial trial of bronchodilators, a chest x-ray, and a subspecialist referral.

No funding was used for this presentation, and Dr. Hysinger reported having no relevant financial disclosures.

 

CHICAGO – Nearly half of all children have wheezing in their first year of life, and one in five have recurrent wheezing episodes, but that doesn’t mean they have asthma, explained Erik Hysinger, MD, MS, of the division of pulmonary medicine at Cincinnati Children’s Hospital.

Localized wheezing is not consistent with asthmatic or viral wheezing, which is typically diffuse and polyphonic, Dr. Hysinger emphasized at the annual meeting of the American Academy of Pediatrics.

“Localized wheezing is less common than diffuse wheezing and typically has a homophonous sound,” Dr. Hysinger said. It also usually arises from a central airway pathology. “High flow rates create loud amplitude sounds.”

iStock/Thinkstock
He discussed different presentations of localized wheezing and reviewed the three categories of differential diagnosis for nonasthmatic, nonviral wheezing: airway occlusion, airway narrowing, or airway compression.

Dr. Hysinger also covered management strategies for focal wheezing, starting with an initial trial of bronchodilators. Any wheezing resulting from a central airway problem, however, isn’t likely to respond to bronchodilators. Standard work-up for any of these causes is usually a chest x-ray, often paired with a bronchoscopy. Persistent wheezing likely needs a chest CT, and many of these conditions will require referral to a subspecialist.

Airway occlusion diagnoses

Four potential causes of an airway blockage are a foreign body, a bronchial cast, mucous plugs, or airway tumors.

A foreign body typically occurs with a cough, wheezing, stridor, and respiratory distress. It is most common in children under age 4 years, usually in those without a history of aspiration, yet providers initially misdiagnose more than 20% of patients with a foreign body. The foreign object – often coins, food, or batteries – frequently ends up in the right main bronchus and may go undetected up to a month, potentially leading to pneumonia, abscess, atelectasis, bronchiectasis, or airway erosion.

Dr. Erik Hysinger
The recommended initial evaluation, a bilateral decubitus chest x-ray, nevertheless cannot rule out a foreign body on its own because the objects may not show up on the films and only two-thirds of cases show an asymmetric hyperinflation. Physicians who suspect that a foreign body may be causing the wheeze should conduct a bronchoscopy. Obviously, the treatment is to remove the object, but providers also should expect to treat possible comorbidities if it took a while to identify and extract the object.

An endobronchial cast is rarer than a foreign body, but can be large enough to completely fill a lung with branching mucin, fibrin, and inflammatory cells. The wheezing sounds homophonous, with a barky or brassy cough accompanied by atelectasis. Dr. Hysinger recommended ordering chest x-ray, echocardiogram, and bronchoscopy. Although often idiopathic, these casts also can result from asthma or another disease: neutrophilic inflammation typically indicates a heart condition whereas asthma or influenza leads to eosinophilic inflammation.

Treatment should involve clearing the airway, followed by hypertonic saline, an inhaled tissue plasminogen activator, and a bronchoscopy for extraction.

Although distinct from endobronchial casts, a mucus plug also presents with wheezing, a cough, and atelectasis, and potentially respiratory distress or failure, and hypoxemia. Mucus plugs are diagnosed with a chest x-ray and flexible bronchoscopy, and then treated by removing the plug and clearing the airway, hypertonic saline, and mucolytics.

The rarest cause of an airway blockage is an airway tumor, often mistaken for asthma. Benign causes include papillomatosis, hemangioma, and hamartomas, while potentially malignant causes include a carcinoid, mucoepidermoid carcinoma, inflammatory myofibromas, and granular cell tumors.

In addition to a chest x-ray and bronchoscopy, a chest CT scan plus a biopsy and resection are necessary to diagnose airway tumors. Treatment will depend on the specific type of tumor identified.

“Overall survival is excellent,” Dr. Hysinger said of children with airway tumors.

Airway narrowing diagnoses

Two possible diagnoses for an intrinsic airway narrowing include bronchomalacia, occurring in only 1 of 2,100 children, and bronchial stenosis.

In bronchomalacia – diagnosed primarily with bronchoscopy – the airway collapses from weakening of the cartilage and posterior membrane. Bronchomalacia sounds like homophonous wheezing with a barky or brassy cough, and it’s frequently accompanied by recurrent bronchitis and/or pneumonia. Intervention is rarely necessary when occurring on its own, but severe cases may require endobronchial stents. Dr. Hysinger also recommended considering ipratroprium instead of albuterol.

Bronchial stenosis involves a fixed narrowing of the bronchi and can be congenital – typically occurring with heart disease – or acquired after an intubation and suction trauma or bronchiolitis obliterans (“popcorn lung”). A chest x-ray and bronchoscopy again are standard, but MRI may be necessary as well. Aside from helping the patient clear the airway, bronchial stenosis typically needs limited management unless the patient is symptomatic. In that case, options include balloon dilation, endobronchial stents, or a slide bronchoplasty.

 

 

Airway compression diagnoses

An extrinsic airway compression could have a vascular cause or could result from pressure by an extrinsic mass or the axial skeleton.

Vascular compression usually occurs due to abnormal vasculature development, particularly with vascular stents, Dr. Hysinger said. The wheezing presents with stridor, feeding intolerance, recurrent infections, and cyanotic episodes. The work-up should include a chest x-ray, bronchoscopy, and a chest CT and/or MRI. A variety of interventions may be necessary to treat it, including an aortopexy, pulmonary artery trunk–pexy, arterioplasty, vessel implantation, or endobronchial stent. Residual malacia may remain after treatment, however.

The most common reasons for airway compression by some kind of mass is a reactive lymphadenopathy, a tumor, or an infection, including tuberculosis or histoplasmosis. Severe narrowing of the airway can lead to respiratory failure, but because the compression can develop slowly, the wheezing can be mistaken for asthma. In addition to a chest CT and bronchoscopy, a patient will need other work-ups depending on the cause. Possibilities include a biopsy, a gastric aspirate (for tuberculosis), a bronchoalveolar lavage, or antibody titers.

Similarly, because therapeutic intervention requires treating the underlying infection, specific treatments will vary. Tumors typically will need resection, chemotherapy, and/or radiation – and, until the airway is fully cleared, the patient may need chronic mechanical ventilation.

Children with severe scoliosis or kyphosis are those most likely to experience airway compression resulting from pressure by the axial skeleton, in which the spine’s curvature directly presses on the airway. In addition to the wheeze, these patients may have respiratory distress or recurrent focal pneumonia, Dr. Hysinger said. The standard work-up involves a chest x-ray, chest CT, spinal MRI, and bronchoscopy.

Consider using spinal rods, but they can both help the condition or potentially exacerbate the compression, Dr. Hysinger said. Either way, children also will need help with airway clearance and coughing.

Dr. Hysinger concluded by reviewing what you may consider changing in your current practice, including the initial trial of bronchodilators, a chest x-ray, and a subspecialist referral.

No funding was used for this presentation, and Dr. Hysinger reported having no relevant financial disclosures.

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Rituximab improves salvage in elderly B-cell lymphoma patients

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In elderly patients with aggressive B-cell lymphomas who experience treatment failure after CHOP or rituximab-CHOP (R-CHOP), the outcomes of subsequent salvage therapy were improved when rituximab was included, results of a retrospective analysis suggest.

“Survival after rituximab-containing salvage therapy was better in all patient groups, supporting the repeated administration of rituximab to all patients needing salvage therapy,” wrote investigator Bertram Glass, MD, of the department of hematology and stem cell transplantation at Helios Klinikum Berlin-Buch, Berlin, and his coauthors (Ann Oncol. 2017 Oct 6. doi: 10.1093/annonc/mdx556).

Dr. Glass and colleagues reviewed data from the randomized RICOVER-60 trial, which included 1,222 patients aged 61-80 years with aggressive B-cell lymphomas who received CHOP or R-CHOP for six or eight cycles. Based on survival outcomes, six cycles of R-CHOP every 2 weeks should be the preferred regimen, investigators wrote when the study results were published in 2008 (Lancet Oncol. 2008;9[2]:105-16. doi: 10.1016/S1470-2045(08)70002-0).

Of 1,222 patients in the RICOVER-60 trial, 301 (24.6%) had treatment failure, of whom 297 could be included in the present analysis.

Rituximab, included in salvage therapy for 57.4% of those evaluable patients, was found to improve the 2-year survival rate from 20.7% to 46.8% (P less than .001), Dr. Glass and his coinvestigators reported.

The benefit of rituximab in the salvage setting was apparent regardless of whether patients received R-CHOP or CHOP as part of their initial therapy in RICOVER-60, they added.

Among patients who had received CHOP as first-line therapy, 2-year overall survival was 49.6% for those who received rituximab in the salvage setting, compared with 19.1% for those who did not (P less than .001), according to the published data. Likewise, in the initial R-CHOP group, 2-year overall survival was 33.1% for rituximab in salvage and 22.5% for no rituximab in salvage (P = .034).

The investigators also looked for differences in prognosis according to specific patient characteristics, including presence of MYC rearrangements and MYC expression by immunohistochemistry.

In patients with MYC translocation at diagnosis, use of rituximab reduced risk of initial treatment failure from 58.8% to 26.3%, according to the investigators. After treatment failure, patients who initially received CHOP had significantly improved 2-year survival if they had MYC translocations or negative MYC immunohistochemistry, though no such association was found for patients who initially received R-CHOP, they wrote.

Dr. Glass and colleagues concluded that new treatment strategies are needed.

“Overall, the outcome of second-line treatment of elderly patients with refractory and relapsed aggressive B-cell lymphoma is disappointing and worse than in younger patients regardless of the modality chosen,” they wrote. “New drugs and treatment modalities with the potential to change the dismal outlook for elderly patients with aggressive B-cell lymphomas are eagerly awaited.”

Dr. Glass and several coauthors reported honoraria, research funding, and consultancies with Roche.

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In elderly patients with aggressive B-cell lymphomas who experience treatment failure after CHOP or rituximab-CHOP (R-CHOP), the outcomes of subsequent salvage therapy were improved when rituximab was included, results of a retrospective analysis suggest.

“Survival after rituximab-containing salvage therapy was better in all patient groups, supporting the repeated administration of rituximab to all patients needing salvage therapy,” wrote investigator Bertram Glass, MD, of the department of hematology and stem cell transplantation at Helios Klinikum Berlin-Buch, Berlin, and his coauthors (Ann Oncol. 2017 Oct 6. doi: 10.1093/annonc/mdx556).

Dr. Glass and colleagues reviewed data from the randomized RICOVER-60 trial, which included 1,222 patients aged 61-80 years with aggressive B-cell lymphomas who received CHOP or R-CHOP for six or eight cycles. Based on survival outcomes, six cycles of R-CHOP every 2 weeks should be the preferred regimen, investigators wrote when the study results were published in 2008 (Lancet Oncol. 2008;9[2]:105-16. doi: 10.1016/S1470-2045(08)70002-0).

Of 1,222 patients in the RICOVER-60 trial, 301 (24.6%) had treatment failure, of whom 297 could be included in the present analysis.

Rituximab, included in salvage therapy for 57.4% of those evaluable patients, was found to improve the 2-year survival rate from 20.7% to 46.8% (P less than .001), Dr. Glass and his coinvestigators reported.

The benefit of rituximab in the salvage setting was apparent regardless of whether patients received R-CHOP or CHOP as part of their initial therapy in RICOVER-60, they added.

Among patients who had received CHOP as first-line therapy, 2-year overall survival was 49.6% for those who received rituximab in the salvage setting, compared with 19.1% for those who did not (P less than .001), according to the published data. Likewise, in the initial R-CHOP group, 2-year overall survival was 33.1% for rituximab in salvage and 22.5% for no rituximab in salvage (P = .034).

The investigators also looked for differences in prognosis according to specific patient characteristics, including presence of MYC rearrangements and MYC expression by immunohistochemistry.

In patients with MYC translocation at diagnosis, use of rituximab reduced risk of initial treatment failure from 58.8% to 26.3%, according to the investigators. After treatment failure, patients who initially received CHOP had significantly improved 2-year survival if they had MYC translocations or negative MYC immunohistochemistry, though no such association was found for patients who initially received R-CHOP, they wrote.

Dr. Glass and colleagues concluded that new treatment strategies are needed.

“Overall, the outcome of second-line treatment of elderly patients with refractory and relapsed aggressive B-cell lymphoma is disappointing and worse than in younger patients regardless of the modality chosen,” they wrote. “New drugs and treatment modalities with the potential to change the dismal outlook for elderly patients with aggressive B-cell lymphomas are eagerly awaited.”

Dr. Glass and several coauthors reported honoraria, research funding, and consultancies with Roche.

 

In elderly patients with aggressive B-cell lymphomas who experience treatment failure after CHOP or rituximab-CHOP (R-CHOP), the outcomes of subsequent salvage therapy were improved when rituximab was included, results of a retrospective analysis suggest.

“Survival after rituximab-containing salvage therapy was better in all patient groups, supporting the repeated administration of rituximab to all patients needing salvage therapy,” wrote investigator Bertram Glass, MD, of the department of hematology and stem cell transplantation at Helios Klinikum Berlin-Buch, Berlin, and his coauthors (Ann Oncol. 2017 Oct 6. doi: 10.1093/annonc/mdx556).

Dr. Glass and colleagues reviewed data from the randomized RICOVER-60 trial, which included 1,222 patients aged 61-80 years with aggressive B-cell lymphomas who received CHOP or R-CHOP for six or eight cycles. Based on survival outcomes, six cycles of R-CHOP every 2 weeks should be the preferred regimen, investigators wrote when the study results were published in 2008 (Lancet Oncol. 2008;9[2]:105-16. doi: 10.1016/S1470-2045(08)70002-0).

Of 1,222 patients in the RICOVER-60 trial, 301 (24.6%) had treatment failure, of whom 297 could be included in the present analysis.

Rituximab, included in salvage therapy for 57.4% of those evaluable patients, was found to improve the 2-year survival rate from 20.7% to 46.8% (P less than .001), Dr. Glass and his coinvestigators reported.

The benefit of rituximab in the salvage setting was apparent regardless of whether patients received R-CHOP or CHOP as part of their initial therapy in RICOVER-60, they added.

Among patients who had received CHOP as first-line therapy, 2-year overall survival was 49.6% for those who received rituximab in the salvage setting, compared with 19.1% for those who did not (P less than .001), according to the published data. Likewise, in the initial R-CHOP group, 2-year overall survival was 33.1% for rituximab in salvage and 22.5% for no rituximab in salvage (P = .034).

The investigators also looked for differences in prognosis according to specific patient characteristics, including presence of MYC rearrangements and MYC expression by immunohistochemistry.

In patients with MYC translocation at diagnosis, use of rituximab reduced risk of initial treatment failure from 58.8% to 26.3%, according to the investigators. After treatment failure, patients who initially received CHOP had significantly improved 2-year survival if they had MYC translocations or negative MYC immunohistochemistry, though no such association was found for patients who initially received R-CHOP, they wrote.

Dr. Glass and colleagues concluded that new treatment strategies are needed.

“Overall, the outcome of second-line treatment of elderly patients with refractory and relapsed aggressive B-cell lymphoma is disappointing and worse than in younger patients regardless of the modality chosen,” they wrote. “New drugs and treatment modalities with the potential to change the dismal outlook for elderly patients with aggressive B-cell lymphomas are eagerly awaited.”

Dr. Glass and several coauthors reported honoraria, research funding, and consultancies with Roche.

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Key clinical point: Rituximab improved salvage therapy for elderly patients with aggressive-B-cell lymphoma who relapsed after CHOP or R-CHOP.

Major finding: Rituximab as part of a salvage regimen improved the 2-year survival rate from 20.7% to 46.8% (P less than .001).

Data source: Retrospective analysis including 297 elderly patients in the RICOVER-60 trial who had progressive, persistent, or relapsed lymphoma.

Disclosures: Dr. Glass and several coauthors reported honoraria, research funding, and consultancies with Roche.

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Robotic-assisted pulmonary lobectomy effective for large tumors

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Robotic-assisted pulmonary lobectomy is a safe and effective way to remove large tumors in patients with non–small cell lung cancer (NSCLC), according to the abstract of a study scheduled to be presented at the CHEST annual meeting.

The study covers a retrospective analysis of 345 NSCLC patients with tumors who underwent robotic-assisted pulmonary lobectomy performed by one surgeon from September 2010 through August 2016. The participants were grouped into the following three cohorts: patients with tumors less than 5 cm in diameter, patients with tumors from 5 to 7 cm, and patients with tumors larger than 7 cm. The researchers excluded patients with pulmonary metastases or benign lesions from the study.

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The 1- and 3-year survival rates for patients with tumors less than 5 cm were 91% and 84%; they were 86% and 75% in patients with tumors from 5 to 7 cm, and 76% and 47% in patients with tumors larger than 7 cm, respectively. A tumor size larger than 7 cm was significantly associated with both worse 1-year and 3-year survival, compared with patients with a tumor less than 5 cm (P = .004).

Patients with smaller tumors were more likely to have simple lobectomy or lobectomy plus wedge, while patients with larger tumors were more likely to require lobectomy with chest wall resection. Increased tumor size was also associated with increased intraoperative estimated blood loss, skin-to-skin operative time, hospital length of stay, and overall conversion to open lobectomy.

There was no association found between tumor size and increased overall intraoperative or postoperative complications, or in-hospital mortality.

Nirav Patel, MD, FCCP, of the Tampa Bay Sleep Center is scheduled to present his abstract on Sunday Oct. 29th, between 2:15 and 2:30 p.m. in Convention Center – 606. Dr. Patel’s research is part of the Cardiothoracic Surgery session, running from 1:30 p.m. to 3:00 p.m. at the CHEST annual meeting.

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Dr. Hossein Almassi, FCCP
Robotic thoracic surgery has gained wide acceptance mostly as a result of a more favorable perioperative hospital course and patient comfort. This report outlines the outcomes of robotic lobectomy performed by one experienced surgeon. As stated by the presenting author during the presentation, standard mediastinal lymph node dissection was part of the procedure. Patient survival was dependent on the tumor size, i.e., the stage of the tumor. With advances in technology, robotic thoracic surgery would potentially be the standard surgical approach in the near future for the treatment of most thoracic pathologies.
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Dr. Hossein Almassi, FCCP
Robotic thoracic surgery has gained wide acceptance mostly as a result of a more favorable perioperative hospital course and patient comfort. This report outlines the outcomes of robotic lobectomy performed by one experienced surgeon. As stated by the presenting author during the presentation, standard mediastinal lymph node dissection was part of the procedure. Patient survival was dependent on the tumor size, i.e., the stage of the tumor. With advances in technology, robotic thoracic surgery would potentially be the standard surgical approach in the near future for the treatment of most thoracic pathologies.
Body

Dr. Hossein Almassi, FCCP
Robotic thoracic surgery has gained wide acceptance mostly as a result of a more favorable perioperative hospital course and patient comfort. This report outlines the outcomes of robotic lobectomy performed by one experienced surgeon. As stated by the presenting author during the presentation, standard mediastinal lymph node dissection was part of the procedure. Patient survival was dependent on the tumor size, i.e., the stage of the tumor. With advances in technology, robotic thoracic surgery would potentially be the standard surgical approach in the near future for the treatment of most thoracic pathologies.
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Comment by G. Hossein Almassi, MD, FCCP
Comment by G. Hossein Almassi, MD, FCCP

 

Robotic-assisted pulmonary lobectomy is a safe and effective way to remove large tumors in patients with non–small cell lung cancer (NSCLC), according to the abstract of a study scheduled to be presented at the CHEST annual meeting.

The study covers a retrospective analysis of 345 NSCLC patients with tumors who underwent robotic-assisted pulmonary lobectomy performed by one surgeon from September 2010 through August 2016. The participants were grouped into the following three cohorts: patients with tumors less than 5 cm in diameter, patients with tumors from 5 to 7 cm, and patients with tumors larger than 7 cm. The researchers excluded patients with pulmonary metastases or benign lesions from the study.

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The 1- and 3-year survival rates for patients with tumors less than 5 cm were 91% and 84%; they were 86% and 75% in patients with tumors from 5 to 7 cm, and 76% and 47% in patients with tumors larger than 7 cm, respectively. A tumor size larger than 7 cm was significantly associated with both worse 1-year and 3-year survival, compared with patients with a tumor less than 5 cm (P = .004).

Patients with smaller tumors were more likely to have simple lobectomy or lobectomy plus wedge, while patients with larger tumors were more likely to require lobectomy with chest wall resection. Increased tumor size was also associated with increased intraoperative estimated blood loss, skin-to-skin operative time, hospital length of stay, and overall conversion to open lobectomy.

There was no association found between tumor size and increased overall intraoperative or postoperative complications, or in-hospital mortality.

Nirav Patel, MD, FCCP, of the Tampa Bay Sleep Center is scheduled to present his abstract on Sunday Oct. 29th, between 2:15 and 2:30 p.m. in Convention Center – 606. Dr. Patel’s research is part of the Cardiothoracic Surgery session, running from 1:30 p.m. to 3:00 p.m. at the CHEST annual meeting.

 

Robotic-assisted pulmonary lobectomy is a safe and effective way to remove large tumors in patients with non–small cell lung cancer (NSCLC), according to the abstract of a study scheduled to be presented at the CHEST annual meeting.

The study covers a retrospective analysis of 345 NSCLC patients with tumors who underwent robotic-assisted pulmonary lobectomy performed by one surgeon from September 2010 through August 2016. The participants were grouped into the following three cohorts: patients with tumors less than 5 cm in diameter, patients with tumors from 5 to 7 cm, and patients with tumors larger than 7 cm. The researchers excluded patients with pulmonary metastases or benign lesions from the study.

Master Video/Shutterstock
The 1- and 3-year survival rates for patients with tumors less than 5 cm were 91% and 84%; they were 86% and 75% in patients with tumors from 5 to 7 cm, and 76% and 47% in patients with tumors larger than 7 cm, respectively. A tumor size larger than 7 cm was significantly associated with both worse 1-year and 3-year survival, compared with patients with a tumor less than 5 cm (P = .004).

Patients with smaller tumors were more likely to have simple lobectomy or lobectomy plus wedge, while patients with larger tumors were more likely to require lobectomy with chest wall resection. Increased tumor size was also associated with increased intraoperative estimated blood loss, skin-to-skin operative time, hospital length of stay, and overall conversion to open lobectomy.

There was no association found between tumor size and increased overall intraoperative or postoperative complications, or in-hospital mortality.

Nirav Patel, MD, FCCP, of the Tampa Bay Sleep Center is scheduled to present his abstract on Sunday Oct. 29th, between 2:15 and 2:30 p.m. in Convention Center – 606. Dr. Patel’s research is part of the Cardiothoracic Surgery session, running from 1:30 p.m. to 3:00 p.m. at the CHEST annual meeting.

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Near-fatal asthma treated effectively by ECMO

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Extracorporeal membrane oxygenation (ECMO) is an effective way to treat near fatal asthma, but physicians must remember the risk of complications, according to an abstract on a study scheduled to be presented at CHEST 2017.

The study covers a retrospective analysis of 371 children with asthma who were treated with ECMO; it used data collected by the Extracorporeal Life Support Organization registry from 1988 to 2016. The median age of the children in the study was 7.5 years; the participant group was 43% white and 39% black, as well as 56% male, according to the abstract, which is mentioned in the program for the CHEST annual meeting.

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Median ECMO time was 123 hours, with 65% of procedures being venovenous (VV) cannulation and 33% of procedures being venoarterial (VA) cannulation. Nearly 90% of patients had hypercarbic respiratory failure, 34% had hypoxic respiratory failure, and 27% had combined respiratory failure. Children with hypercarbic respiratory failure were more likely to receive VV cannulation (P = .003), while children with hypoxic or combined respiratory failure were more likely to receive VA cannulation, (P = .0008 and .01, respectively).

About 80% of children experienced at least one complication, with 20% experiencing three or more. Children who had three or more complications were significantly less likely to experience lung recovery.

Of the children who received VV cannulation, 90% experienced lung recovery, whereas only 69% of children who received VA cannulation recovered. (P less than .0001). VA cannulation was also associated with a higher risk of neurological complications, while those who received VV cannulation were significantly more likely to survive.

The abstract is scheduled to be presented on Sunday Oct. 29 from 2:30 p.m. to 2:45 p.m. in Room 603 of Toronto Convention Centre South Building as part of the Acute Lung Injury & Respiratory Failure session, which will run from 1:30 p.m. to 3 p.m.

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Extracorporeal membrane oxygenation (ECMO) is an effective way to treat near fatal asthma, but physicians must remember the risk of complications, according to an abstract on a study scheduled to be presented at CHEST 2017.

The study covers a retrospective analysis of 371 children with asthma who were treated with ECMO; it used data collected by the Extracorporeal Life Support Organization registry from 1988 to 2016. The median age of the children in the study was 7.5 years; the participant group was 43% white and 39% black, as well as 56% male, according to the abstract, which is mentioned in the program for the CHEST annual meeting.

MattZ90/thinkstock
Median ECMO time was 123 hours, with 65% of procedures being venovenous (VV) cannulation and 33% of procedures being venoarterial (VA) cannulation. Nearly 90% of patients had hypercarbic respiratory failure, 34% had hypoxic respiratory failure, and 27% had combined respiratory failure. Children with hypercarbic respiratory failure were more likely to receive VV cannulation (P = .003), while children with hypoxic or combined respiratory failure were more likely to receive VA cannulation, (P = .0008 and .01, respectively).

About 80% of children experienced at least one complication, with 20% experiencing three or more. Children who had three or more complications were significantly less likely to experience lung recovery.

Of the children who received VV cannulation, 90% experienced lung recovery, whereas only 69% of children who received VA cannulation recovered. (P less than .0001). VA cannulation was also associated with a higher risk of neurological complications, while those who received VV cannulation were significantly more likely to survive.

The abstract is scheduled to be presented on Sunday Oct. 29 from 2:30 p.m. to 2:45 p.m. in Room 603 of Toronto Convention Centre South Building as part of the Acute Lung Injury & Respiratory Failure session, which will run from 1:30 p.m. to 3 p.m.

Extracorporeal membrane oxygenation (ECMO) is an effective way to treat near fatal asthma, but physicians must remember the risk of complications, according to an abstract on a study scheduled to be presented at CHEST 2017.

The study covers a retrospective analysis of 371 children with asthma who were treated with ECMO; it used data collected by the Extracorporeal Life Support Organization registry from 1988 to 2016. The median age of the children in the study was 7.5 years; the participant group was 43% white and 39% black, as well as 56% male, according to the abstract, which is mentioned in the program for the CHEST annual meeting.

MattZ90/thinkstock
Median ECMO time was 123 hours, with 65% of procedures being venovenous (VV) cannulation and 33% of procedures being venoarterial (VA) cannulation. Nearly 90% of patients had hypercarbic respiratory failure, 34% had hypoxic respiratory failure, and 27% had combined respiratory failure. Children with hypercarbic respiratory failure were more likely to receive VV cannulation (P = .003), while children with hypoxic or combined respiratory failure were more likely to receive VA cannulation, (P = .0008 and .01, respectively).

About 80% of children experienced at least one complication, with 20% experiencing three or more. Children who had three or more complications were significantly less likely to experience lung recovery.

Of the children who received VV cannulation, 90% experienced lung recovery, whereas only 69% of children who received VA cannulation recovered. (P less than .0001). VA cannulation was also associated with a higher risk of neurological complications, while those who received VV cannulation were significantly more likely to survive.

The abstract is scheduled to be presented on Sunday Oct. 29 from 2:30 p.m. to 2:45 p.m. in Room 603 of Toronto Convention Centre South Building as part of the Acute Lung Injury & Respiratory Failure session, which will run from 1:30 p.m. to 3 p.m.

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How Do Type 2 Diabetes and Thyroid Disorder Interact?

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Researchers analyzed an 11-year study to better understand the interaction between type 2 diabetes mellitus in patients with thyroid disorders.

Although studies have examined the relationship between thyroid disorder (TD) and type 1 diabetes mellitus (T1DM), the information on TD and type 2 diabetes mellitus (T2DM) is limited, say researchers from Shahid Beheshti University of Medical Sciences and Aja University of Medical Science in Tehran, Iran, who report on an 11-year follow-up from the Tehran Thyroid Study. However, undetected TDs may compromise metabolic control of patients with diabetes mellitus (DM), impaired glucose tolerance, or impaired fasting glucose, the researchers point out. Undetected TDs also may increase the risk of cardiovascular diseases. And DM and prediabetes can affect thyroid tests.

The researchers evaluated 435 patients with DM, 286 with prediabetes, and 989 healthy controls. They conducted follow-up assessments every 3 years. About 19% of both the diabetic and prediabetic groups had TD, as did about 14% of the healthy controls. However, after adjusting for age, sex, smoking, blood pressure, body mass index, thyroid peroxidase antibody (TPOAb), thyrotropin (TSH), insulin resistance index, triglycerides, and cholesterol, no significant difference was found among the 3 groups. The mean incidence of TD was 14, 18, and 21 per 1000 patients per year in patients with DM, prediabetes, and healthy controls, respectively.

As in other studies, subclinical hypothyroidism and clinical hyperthyroidism were the most and the least common TD in patients with DM. Baseline TSH > 1.94 mU/L was predictive of TD with 70% sensitivity and specificity and had better predictive value than TPOAb . The researchers say conducting screening tests in all patients is not recommended except in those with TPOAb ≥ 401 U/mL or TSH > 1.94 mU/L.

 

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Gholampour Dehaki M, Amouzegar A, Delshad H, Mehrabi Y, Tohidi M, Azizi F. PLoS One. 2017;12(10): e0184808.
doi: 10.1371/journal.pone.0184808.

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Researchers analyzed an 11-year study to better understand the interaction between type 2 diabetes mellitus in patients with thyroid disorders.
Researchers analyzed an 11-year study to better understand the interaction between type 2 diabetes mellitus in patients with thyroid disorders.

Although studies have examined the relationship between thyroid disorder (TD) and type 1 diabetes mellitus (T1DM), the information on TD and type 2 diabetes mellitus (T2DM) is limited, say researchers from Shahid Beheshti University of Medical Sciences and Aja University of Medical Science in Tehran, Iran, who report on an 11-year follow-up from the Tehran Thyroid Study. However, undetected TDs may compromise metabolic control of patients with diabetes mellitus (DM), impaired glucose tolerance, or impaired fasting glucose, the researchers point out. Undetected TDs also may increase the risk of cardiovascular diseases. And DM and prediabetes can affect thyroid tests.

The researchers evaluated 435 patients with DM, 286 with prediabetes, and 989 healthy controls. They conducted follow-up assessments every 3 years. About 19% of both the diabetic and prediabetic groups had TD, as did about 14% of the healthy controls. However, after adjusting for age, sex, smoking, blood pressure, body mass index, thyroid peroxidase antibody (TPOAb), thyrotropin (TSH), insulin resistance index, triglycerides, and cholesterol, no significant difference was found among the 3 groups. The mean incidence of TD was 14, 18, and 21 per 1000 patients per year in patients with DM, prediabetes, and healthy controls, respectively.

As in other studies, subclinical hypothyroidism and clinical hyperthyroidism were the most and the least common TD in patients with DM. Baseline TSH > 1.94 mU/L was predictive of TD with 70% sensitivity and specificity and had better predictive value than TPOAb . The researchers say conducting screening tests in all patients is not recommended except in those with TPOAb ≥ 401 U/mL or TSH > 1.94 mU/L.

 

Source:

Gholampour Dehaki M, Amouzegar A, Delshad H, Mehrabi Y, Tohidi M, Azizi F. PLoS One. 2017;12(10): e0184808.
doi: 10.1371/journal.pone.0184808.

Although studies have examined the relationship between thyroid disorder (TD) and type 1 diabetes mellitus (T1DM), the information on TD and type 2 diabetes mellitus (T2DM) is limited, say researchers from Shahid Beheshti University of Medical Sciences and Aja University of Medical Science in Tehran, Iran, who report on an 11-year follow-up from the Tehran Thyroid Study. However, undetected TDs may compromise metabolic control of patients with diabetes mellitus (DM), impaired glucose tolerance, or impaired fasting glucose, the researchers point out. Undetected TDs also may increase the risk of cardiovascular diseases. And DM and prediabetes can affect thyroid tests.

The researchers evaluated 435 patients with DM, 286 with prediabetes, and 989 healthy controls. They conducted follow-up assessments every 3 years. About 19% of both the diabetic and prediabetic groups had TD, as did about 14% of the healthy controls. However, after adjusting for age, sex, smoking, blood pressure, body mass index, thyroid peroxidase antibody (TPOAb), thyrotropin (TSH), insulin resistance index, triglycerides, and cholesterol, no significant difference was found among the 3 groups. The mean incidence of TD was 14, 18, and 21 per 1000 patients per year in patients with DM, prediabetes, and healthy controls, respectively.

As in other studies, subclinical hypothyroidism and clinical hyperthyroidism were the most and the least common TD in patients with DM. Baseline TSH > 1.94 mU/L was predictive of TD with 70% sensitivity and specificity and had better predictive value than TPOAb . The researchers say conducting screening tests in all patients is not recommended except in those with TPOAb ≥ 401 U/mL or TSH > 1.94 mU/L.

 

Source:

Gholampour Dehaki M, Amouzegar A, Delshad H, Mehrabi Y, Tohidi M, Azizi F. PLoS One. 2017;12(10): e0184808.
doi: 10.1371/journal.pone.0184808.

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FDA approves second CAR-T therapy

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A second chimeric antigen receptor (CAR) T-cell therapy has gained FDA approval, this time for the treatment of large B-cell lymphoma in adults.

“Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “This approval demonstrates the continued momentum of this promising new area of medicine, and we’re committed to supporting and helping expedite the development of these products.”

Axicabtagene ciloleucel, to be marketed at Yescarta by Kite Pharma, is approved for use in adults with large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL). Patients must have failed at least two other treatments before axicabtagene ciloleucel can be tried.

Approval was based on ZUMA-1, a multicenter clinical trial of 101 adults with refractory or relapsed large B-cell lymphoma. Almost three-quarters (72%) of patients responded, including 51% who achieved complete remission.

CAR-T therapy can cause severe, life-threatening side effects, most notably cytokine release syndrome (CRS) and neurologic toxicities, for which axicabtagene ciloleucel will carry a boxed warning and will come with a risk evaluation and mitigation strategy (REMS), according to the FDA.

The list price for a single treatment of axicabtagene ciloleucel is $373,000, according to the manufacturer.

“We will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine,” Dr. Gottlieb said in a statement. “That policy will also clarify how we will apply our expedited programs to breakthrough products that use CAR-T cells and other gene therapies. We remain committed to supporting the efficient development of safe and effective treatments that leverage these new scientific platforms.”

Axicabtagene ciloleucel was developed by Kite Pharma, which was acquired recently by Gilead Sciences.

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A second chimeric antigen receptor (CAR) T-cell therapy has gained FDA approval, this time for the treatment of large B-cell lymphoma in adults.

“Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “This approval demonstrates the continued momentum of this promising new area of medicine, and we’re committed to supporting and helping expedite the development of these products.”

Axicabtagene ciloleucel, to be marketed at Yescarta by Kite Pharma, is approved for use in adults with large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL). Patients must have failed at least two other treatments before axicabtagene ciloleucel can be tried.

Approval was based on ZUMA-1, a multicenter clinical trial of 101 adults with refractory or relapsed large B-cell lymphoma. Almost three-quarters (72%) of patients responded, including 51% who achieved complete remission.

CAR-T therapy can cause severe, life-threatening side effects, most notably cytokine release syndrome (CRS) and neurologic toxicities, for which axicabtagene ciloleucel will carry a boxed warning and will come with a risk evaluation and mitigation strategy (REMS), according to the FDA.

The list price for a single treatment of axicabtagene ciloleucel is $373,000, according to the manufacturer.

“We will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine,” Dr. Gottlieb said in a statement. “That policy will also clarify how we will apply our expedited programs to breakthrough products that use CAR-T cells and other gene therapies. We remain committed to supporting the efficient development of safe and effective treatments that leverage these new scientific platforms.”

Axicabtagene ciloleucel was developed by Kite Pharma, which was acquired recently by Gilead Sciences.

 

A second chimeric antigen receptor (CAR) T-cell therapy has gained FDA approval, this time for the treatment of large B-cell lymphoma in adults.

“Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “This approval demonstrates the continued momentum of this promising new area of medicine, and we’re committed to supporting and helping expedite the development of these products.”

Axicabtagene ciloleucel, to be marketed at Yescarta by Kite Pharma, is approved for use in adults with large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL). Patients must have failed at least two other treatments before axicabtagene ciloleucel can be tried.

Approval was based on ZUMA-1, a multicenter clinical trial of 101 adults with refractory or relapsed large B-cell lymphoma. Almost three-quarters (72%) of patients responded, including 51% who achieved complete remission.

CAR-T therapy can cause severe, life-threatening side effects, most notably cytokine release syndrome (CRS) and neurologic toxicities, for which axicabtagene ciloleucel will carry a boxed warning and will come with a risk evaluation and mitigation strategy (REMS), according to the FDA.

The list price for a single treatment of axicabtagene ciloleucel is $373,000, according to the manufacturer.

“We will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine,” Dr. Gottlieb said in a statement. “That policy will also clarify how we will apply our expedited programs to breakthrough products that use CAR-T cells and other gene therapies. We remain committed to supporting the efficient development of safe and effective treatments that leverage these new scientific platforms.”

Axicabtagene ciloleucel was developed by Kite Pharma, which was acquired recently by Gilead Sciences.

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VA Partnership Expands Access to Lung Screening Programs

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The partnership aims to increase access to lung cancer screenings by expanding programs throughout the VA.

Lung cancer has an 80% cure rate when caught early, and screening programs are key to providing this chance. The VA and the Bristol-Myers Squibb Foundation have established the VA-Partnership to increase Access to Lung Screening (VA-PALS) Implementation Network.

The initiative builds upon experience gained from other screening programs, the VA says, including those of the VA’s Office of Rural Health, which is supporting the project’s goal to reach veterans living in rural areas. It also adds to a portfolio of other major VA lung cancer initiatives, including the VALOR Trial (Veterans Affairs Lung Cancer Or Stereotactic Radiotherapy) and the APOLLO Network (Applied Proteogenomics OrganizationaL Learning and Outcomes).

“Research shows that with comprehensive lung screening programs, early identification of lung cancer leads to more effective treatments and, ultimately, saves lives,” said John Damonti, president of Bristol-Myers Squibb Foundation, the project’s sponsor.

The project will launch with lung-screening services at the Phoenix VA Health Care System in Arizona by December 2017, and then extend these services to 9 additional VA medical facilities starting in 2018.

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The partnership aims to increase access to lung cancer screenings by expanding programs throughout the VA.
The partnership aims to increase access to lung cancer screenings by expanding programs throughout the VA.

Lung cancer has an 80% cure rate when caught early, and screening programs are key to providing this chance. The VA and the Bristol-Myers Squibb Foundation have established the VA-Partnership to increase Access to Lung Screening (VA-PALS) Implementation Network.

The initiative builds upon experience gained from other screening programs, the VA says, including those of the VA’s Office of Rural Health, which is supporting the project’s goal to reach veterans living in rural areas. It also adds to a portfolio of other major VA lung cancer initiatives, including the VALOR Trial (Veterans Affairs Lung Cancer Or Stereotactic Radiotherapy) and the APOLLO Network (Applied Proteogenomics OrganizationaL Learning and Outcomes).

“Research shows that with comprehensive lung screening programs, early identification of lung cancer leads to more effective treatments and, ultimately, saves lives,” said John Damonti, president of Bristol-Myers Squibb Foundation, the project’s sponsor.

The project will launch with lung-screening services at the Phoenix VA Health Care System in Arizona by December 2017, and then extend these services to 9 additional VA medical facilities starting in 2018.

Lung cancer has an 80% cure rate when caught early, and screening programs are key to providing this chance. The VA and the Bristol-Myers Squibb Foundation have established the VA-Partnership to increase Access to Lung Screening (VA-PALS) Implementation Network.

The initiative builds upon experience gained from other screening programs, the VA says, including those of the VA’s Office of Rural Health, which is supporting the project’s goal to reach veterans living in rural areas. It also adds to a portfolio of other major VA lung cancer initiatives, including the VALOR Trial (Veterans Affairs Lung Cancer Or Stereotactic Radiotherapy) and the APOLLO Network (Applied Proteogenomics OrganizationaL Learning and Outcomes).

“Research shows that with comprehensive lung screening programs, early identification of lung cancer leads to more effective treatments and, ultimately, saves lives,” said John Damonti, president of Bristol-Myers Squibb Foundation, the project’s sponsor.

The project will launch with lung-screening services at the Phoenix VA Health Care System in Arizona by December 2017, and then extend these services to 9 additional VA medical facilities starting in 2018.

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Flu study shows overall efficacy of LAIV, but weakness for one strain

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Trivalent and quadrivalent inactivated influenza vaccine (IIV) and quadrivalent live attenuated influenza vaccine (LAIV) all gave statistically significant protection against any flu in U.S. children aged 2-17 years in 2015-2016, Katherine A. Poehling, MD, of Wake Forest University, Winston-Salem, N.C., and her associates reported in a study of more than 1,000 children.

“This study also adds to the clinical evidence suggesting that effectiveness of LAIV against influenza A(H1N1)pdm09 strains has been lower than observed with IIV since the 2009 influenza A(H1N1) pandemic,” the researchers concluded.

Cynthia Goldsmith/CDC photo #10073
This negative-stained transmission electron micrograph (TEM) depicts the ultrastructural details of an influenza virus particle, or “virion.”
More than 1,000 children aged 2-17 years seeking outpatient medical care for febrile acute respiratory illness were recruited in Florida, Minnesota, North Carolina, Ohio, Oregon, Tennessee, Texas, and Wisconsin in the 2015-2016 flu season; children were required to have fever and illness onset of less than 5 days, and 84% of children had cough. A nasal swab was collected and tested for influenza and other viruses; medical records were checked for flu vaccination dates and vaccine types.

“The 2015-2016 season northern hemisphere trivalent IIV included A/California/7/2009 (H1N1)-like virus, a new A/Switzerland/9715293/2013 (H3N2)-like virus, and a new B/Phuket/3073/2013-like virus (Yamagata lineage),” the investigators noted. “Quadrivalent IIV was similar to trivalent IIV and also included B/Brisbane/60/2008-like virus (Victoria lineage). LAIV was similar to quadrivalent IIV, except that it contained A/Bolivia/559/2013.”

Of the 1,012 children enrolled, 59% were unvaccinated, 10% were given LAIV, 10% received trivalent IIV, 20% were given quadrivalent IIV, and 1% received IIV of “unknown valence.”

Vaccine efficacy against any influenza was 46% for LAIV and 65% for IIV, compared with no vaccination. But only IIV gave “significant protection against influenza A(H1N1)pdm09 strains in the total study population,” Dr. Poehling and her associates said. Vaccine efficacy against influenza A(H1N1)pdm09 strains was 50% for LAIV and 71% for IIV.

Read more in Clinical Infectious Diseases (2017 Oct 4. doi: 10.1093/cid/cix869).
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Trivalent and quadrivalent inactivated influenza vaccine (IIV) and quadrivalent live attenuated influenza vaccine (LAIV) all gave statistically significant protection against any flu in U.S. children aged 2-17 years in 2015-2016, Katherine A. Poehling, MD, of Wake Forest University, Winston-Salem, N.C., and her associates reported in a study of more than 1,000 children.

“This study also adds to the clinical evidence suggesting that effectiveness of LAIV against influenza A(H1N1)pdm09 strains has been lower than observed with IIV since the 2009 influenza A(H1N1) pandemic,” the researchers concluded.

Cynthia Goldsmith/CDC photo #10073
This negative-stained transmission electron micrograph (TEM) depicts the ultrastructural details of an influenza virus particle, or “virion.”
More than 1,000 children aged 2-17 years seeking outpatient medical care for febrile acute respiratory illness were recruited in Florida, Minnesota, North Carolina, Ohio, Oregon, Tennessee, Texas, and Wisconsin in the 2015-2016 flu season; children were required to have fever and illness onset of less than 5 days, and 84% of children had cough. A nasal swab was collected and tested for influenza and other viruses; medical records were checked for flu vaccination dates and vaccine types.

“The 2015-2016 season northern hemisphere trivalent IIV included A/California/7/2009 (H1N1)-like virus, a new A/Switzerland/9715293/2013 (H3N2)-like virus, and a new B/Phuket/3073/2013-like virus (Yamagata lineage),” the investigators noted. “Quadrivalent IIV was similar to trivalent IIV and also included B/Brisbane/60/2008-like virus (Victoria lineage). LAIV was similar to quadrivalent IIV, except that it contained A/Bolivia/559/2013.”

Of the 1,012 children enrolled, 59% were unvaccinated, 10% were given LAIV, 10% received trivalent IIV, 20% were given quadrivalent IIV, and 1% received IIV of “unknown valence.”

Vaccine efficacy against any influenza was 46% for LAIV and 65% for IIV, compared with no vaccination. But only IIV gave “significant protection against influenza A(H1N1)pdm09 strains in the total study population,” Dr. Poehling and her associates said. Vaccine efficacy against influenza A(H1N1)pdm09 strains was 50% for LAIV and 71% for IIV.

Read more in Clinical Infectious Diseases (2017 Oct 4. doi: 10.1093/cid/cix869).

Trivalent and quadrivalent inactivated influenza vaccine (IIV) and quadrivalent live attenuated influenza vaccine (LAIV) all gave statistically significant protection against any flu in U.S. children aged 2-17 years in 2015-2016, Katherine A. Poehling, MD, of Wake Forest University, Winston-Salem, N.C., and her associates reported in a study of more than 1,000 children.

“This study also adds to the clinical evidence suggesting that effectiveness of LAIV against influenza A(H1N1)pdm09 strains has been lower than observed with IIV since the 2009 influenza A(H1N1) pandemic,” the researchers concluded.

Cynthia Goldsmith/CDC photo #10073
This negative-stained transmission electron micrograph (TEM) depicts the ultrastructural details of an influenza virus particle, or “virion.”
More than 1,000 children aged 2-17 years seeking outpatient medical care for febrile acute respiratory illness were recruited in Florida, Minnesota, North Carolina, Ohio, Oregon, Tennessee, Texas, and Wisconsin in the 2015-2016 flu season; children were required to have fever and illness onset of less than 5 days, and 84% of children had cough. A nasal swab was collected and tested for influenza and other viruses; medical records were checked for flu vaccination dates and vaccine types.

“The 2015-2016 season northern hemisphere trivalent IIV included A/California/7/2009 (H1N1)-like virus, a new A/Switzerland/9715293/2013 (H3N2)-like virus, and a new B/Phuket/3073/2013-like virus (Yamagata lineage),” the investigators noted. “Quadrivalent IIV was similar to trivalent IIV and also included B/Brisbane/60/2008-like virus (Victoria lineage). LAIV was similar to quadrivalent IIV, except that it contained A/Bolivia/559/2013.”

Of the 1,012 children enrolled, 59% were unvaccinated, 10% were given LAIV, 10% received trivalent IIV, 20% were given quadrivalent IIV, and 1% received IIV of “unknown valence.”

Vaccine efficacy against any influenza was 46% for LAIV and 65% for IIV, compared with no vaccination. But only IIV gave “significant protection against influenza A(H1N1)pdm09 strains in the total study population,” Dr. Poehling and her associates said. Vaccine efficacy against influenza A(H1N1)pdm09 strains was 50% for LAIV and 71% for IIV.

Read more in Clinical Infectious Diseases (2017 Oct 4. doi: 10.1093/cid/cix869).
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Guidelines cut acute chest syndrome hospital returns in pediatric sickle cell

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Children with sickle cell disease who experience acute chest syndrome benefit from the current guideline-recommended antibiotic regimen, based on data from more than 7,000 patients.

Although acute chest syndrome (ACS) is among the most common complications of sickle cell disease (SCD), data on the effectiveness of the recommended antibiotic therapies (macrolides and cephalosporins) are lacking, wrote David G. Bundy, MD, of the Medical University of South Carolina, Charleston, and colleagues. ACS often leads to intensive hospital care and 1%-2% morbidity, they noted.

The most recent guidelines from the National Heart, Lung, and Blood Institute call for “an intravenous cephalosporin and an oral macrolide antibiotic,” the researchers said.

To determine the impact of antibiotic use as directed on reducing hospital readmissions in young SCD patients, the researchers reviewed data from 14,480 hospitalizations for ACS involving 7,178 children and young adults aged 0-22 years seen at 41 hospitals in the United States (JAMA Pediatr. 2017 Sep 11. doi: 10.1001/jamapediatrics.2017.2526).

CDC/Janice Haney Carr
Overall, 74% of the patients were treated with antibiotics according to the guidelines, but use of guideline-recommended antibiotics ranged from 24% to 90% across the participating hospitals.

“This high level of interhospital variation also suggests possible clinician disagreement regarding the ideal antibiotic treatment for children with ACS,” the researchers wrote.

Rates of all-cause readmission and 30-day ACS-related readmission were significantly lower among patients who received the recommended antibiotics (odds ratio, 0.50 and 0.71, respectively). Children aged 5-9 years were most likely to receive the recommended antibiotics (80%), while young adults aged 19-22 years were the least likely (64%).

The findings were limited by several factors, including coding errors and incomplete clinical information, the researchers noted. But the results suggest that the guideline-recommended antibiotics are effective, “so more robust dissemination and implementation of existing treatment guidelines may reduce readmissions in this high-risk population,” they said.

The researchers had no financial conflicts to disclose. Study coauthor Staci Arnold, MD, was supported in part by the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program.

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Children with sickle cell disease who experience acute chest syndrome benefit from the current guideline-recommended antibiotic regimen, based on data from more than 7,000 patients.

Although acute chest syndrome (ACS) is among the most common complications of sickle cell disease (SCD), data on the effectiveness of the recommended antibiotic therapies (macrolides and cephalosporins) are lacking, wrote David G. Bundy, MD, of the Medical University of South Carolina, Charleston, and colleagues. ACS often leads to intensive hospital care and 1%-2% morbidity, they noted.

The most recent guidelines from the National Heart, Lung, and Blood Institute call for “an intravenous cephalosporin and an oral macrolide antibiotic,” the researchers said.

To determine the impact of antibiotic use as directed on reducing hospital readmissions in young SCD patients, the researchers reviewed data from 14,480 hospitalizations for ACS involving 7,178 children and young adults aged 0-22 years seen at 41 hospitals in the United States (JAMA Pediatr. 2017 Sep 11. doi: 10.1001/jamapediatrics.2017.2526).

CDC/Janice Haney Carr
Overall, 74% of the patients were treated with antibiotics according to the guidelines, but use of guideline-recommended antibiotics ranged from 24% to 90% across the participating hospitals.

“This high level of interhospital variation also suggests possible clinician disagreement regarding the ideal antibiotic treatment for children with ACS,” the researchers wrote.

Rates of all-cause readmission and 30-day ACS-related readmission were significantly lower among patients who received the recommended antibiotics (odds ratio, 0.50 and 0.71, respectively). Children aged 5-9 years were most likely to receive the recommended antibiotics (80%), while young adults aged 19-22 years were the least likely (64%).

The findings were limited by several factors, including coding errors and incomplete clinical information, the researchers noted. But the results suggest that the guideline-recommended antibiotics are effective, “so more robust dissemination and implementation of existing treatment guidelines may reduce readmissions in this high-risk population,” they said.

The researchers had no financial conflicts to disclose. Study coauthor Staci Arnold, MD, was supported in part by the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program.

 

Children with sickle cell disease who experience acute chest syndrome benefit from the current guideline-recommended antibiotic regimen, based on data from more than 7,000 patients.

Although acute chest syndrome (ACS) is among the most common complications of sickle cell disease (SCD), data on the effectiveness of the recommended antibiotic therapies (macrolides and cephalosporins) are lacking, wrote David G. Bundy, MD, of the Medical University of South Carolina, Charleston, and colleagues. ACS often leads to intensive hospital care and 1%-2% morbidity, they noted.

The most recent guidelines from the National Heart, Lung, and Blood Institute call for “an intravenous cephalosporin and an oral macrolide antibiotic,” the researchers said.

To determine the impact of antibiotic use as directed on reducing hospital readmissions in young SCD patients, the researchers reviewed data from 14,480 hospitalizations for ACS involving 7,178 children and young adults aged 0-22 years seen at 41 hospitals in the United States (JAMA Pediatr. 2017 Sep 11. doi: 10.1001/jamapediatrics.2017.2526).

CDC/Janice Haney Carr
Overall, 74% of the patients were treated with antibiotics according to the guidelines, but use of guideline-recommended antibiotics ranged from 24% to 90% across the participating hospitals.

“This high level of interhospital variation also suggests possible clinician disagreement regarding the ideal antibiotic treatment for children with ACS,” the researchers wrote.

Rates of all-cause readmission and 30-day ACS-related readmission were significantly lower among patients who received the recommended antibiotics (odds ratio, 0.50 and 0.71, respectively). Children aged 5-9 years were most likely to receive the recommended antibiotics (80%), while young adults aged 19-22 years were the least likely (64%).

The findings were limited by several factors, including coding errors and incomplete clinical information, the researchers noted. But the results suggest that the guideline-recommended antibiotics are effective, “so more robust dissemination and implementation of existing treatment guidelines may reduce readmissions in this high-risk population,” they said.

The researchers had no financial conflicts to disclose. Study coauthor Staci Arnold, MD, was supported in part by the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program.

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Key clinical point: Treatment with the recommended antibiotics was effective in reducing hospital readmissions for acute chest syndrome in children and young adults up to age 22 years with sickle cell disease.

Major finding: Hospital readmission for 30-day acute chest syndrome and all-cause readmission were significantly lower (odds ratio, 0.71 and 0.50, respectively) among children with sickle cell disease who received antibiotics (macrolides and cephalosporins) according to current guidelines, compared with those who did not.

Data source: A retrospective, multicenter study of 14,480 hospitalizations at 41 locations involving 7,178 children and young adults aged 0-22 years.

Disclosures: The researchers had no financial conflicts to disclose. Study coauthor Staci Arnold, MD, was supported in part by the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program.

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FDA Approves Patient-Assisted Mammography

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New digital mammography system allows the patient to have some say on the amount of pressure that is applied during an exam.

Women of all ages and sizes will be glad to know that they now have some say in the amount of pressure applied to the breast during a mammography. The FDA has cleared Senographe Pristina with Self-Compression, the first patient-assisted 2D digital mammography system.

Digital mammograms use a computer along with x-rays. During an exam with the new system, the technologist positions the patient and initiates compression, then guides the patient in using the handheld wireless remote control to adjust the compression to a comfortable level. The technologist makes the final decision on whether the compression is adequate.

A clinical validation demonstrated that the addition of a remote to allow self-compression did not negatively affect image quality. Nor did allowing the patient to help with adjustments make the exam take significantly longer.

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New digital mammography system allows the patient to have some say on the amount of pressure that is applied during an exam.
New digital mammography system allows the patient to have some say on the amount of pressure that is applied during an exam.

Women of all ages and sizes will be glad to know that they now have some say in the amount of pressure applied to the breast during a mammography. The FDA has cleared Senographe Pristina with Self-Compression, the first patient-assisted 2D digital mammography system.

Digital mammograms use a computer along with x-rays. During an exam with the new system, the technologist positions the patient and initiates compression, then guides the patient in using the handheld wireless remote control to adjust the compression to a comfortable level. The technologist makes the final decision on whether the compression is adequate.

A clinical validation demonstrated that the addition of a remote to allow self-compression did not negatively affect image quality. Nor did allowing the patient to help with adjustments make the exam take significantly longer.

Women of all ages and sizes will be glad to know that they now have some say in the amount of pressure applied to the breast during a mammography. The FDA has cleared Senographe Pristina with Self-Compression, the first patient-assisted 2D digital mammography system.

Digital mammograms use a computer along with x-rays. During an exam with the new system, the technologist positions the patient and initiates compression, then guides the patient in using the handheld wireless remote control to adjust the compression to a comfortable level. The technologist makes the final decision on whether the compression is adequate.

A clinical validation demonstrated that the addition of a remote to allow self-compression did not negatively affect image quality. Nor did allowing the patient to help with adjustments make the exam take significantly longer.

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