Amy Karon

Almost 42% of patients who survived severe sepsis and were rehospitalized within 90 days had conditions for which appropriate outpatient care can potentially prevent readmissions, investigators wrote online March 10 in a letter to JAMA.

These “ambulatory care sensitive conditions” (or ACSCs) accounted for significantly more readmissions among sepsis survivors, compared with patients whose initial hospitalizations were for other reasons, said Dr. Hallie Prescott of the University of Michigan, Ann Arbor, and her associates.

The findings support exploring “the feasibility and potential benefit of post-discharge interventions that are tailored to patients’ personalized risk for a limited number of common conditions,” the investigators said (JAMA 2015;313:1055-7).Patients who survive severe sepsis are often rehospitalized soon afterward, but fairly little is known about the reasons for rehospitalization or whether better outpatient care might prevent some of these readmissions, the researchers said. To explore these questions, they used the Medicare-linked U.S. Health and Retirement Study to study hospitalization codes that indicated sepsis – that is, both acute infection and organ dysfunction. They also compared survivors of severe sepsis with patients who were discharged after hospitalization for 15 other common conditions.

Severe sepsis did not seem to increase the likelihood of rehospitalization – about 42% of both groups of patients were readmitted within 90 days, Dr. Prescott and her associates said. However, ACSCs such as heart failure, pneumonia, worsening chronic obstructive pulmonary disease, and urinary tract infections accounted for about 42% of 90-day readmissions among sepsis survivors (95% confidence interval, 39.2% to 44.1%), versus 37% of the comparison group (95% confidence interval, 34.8%-39.5%; P = .009).

Further, survivors of severe sepsis (12%; 95% confidence interval, 10.6%-13.1%) were more likely than other patients (8%; 95% CI, 7.0%-9.1%; P < .001) to be readmitted with another primary infection, including sepsis, pneumonia, urinary tract infections, and skin and soft tissue infections.

“A limitation of the present study is that we inferred the potential preventability of re-hospitalizations by measuring readmissions for ACSCs,” the researchers noted. “Whether these diagnoses represent preventable admissions, especially after sepsis, is not clear.”

The National Institutes of Health and the Department of Veterans Affairs Health Services Research & Development Service funded the study. The authors reported having no relevant conflicts of interest.

Almost 42% of patients who survived severe sepsis and were rehospitalized within 90 days had conditions for which appropriate outpatient care can potentially prevent readmissions, investigators wrote online March 10 in a letter to JAMA.

These “ambulatory care sensitive conditions” (or ACSCs) accounted for significantly more readmissions among sepsis survivors, compared with patients whose initial hospitalizations were for other reasons, said Dr. Hallie Prescott of the University of Michigan, Ann Arbor, and her associates.

The findings support exploring “the feasibility and potential benefit of post-discharge interventions that are tailored to patients’ personalized risk for a limited number of common conditions,” the investigators said (JAMA 2015;313:1055-7).Patients who survive severe sepsis are often rehospitalized soon afterward, but fairly little is known about the reasons for rehospitalization or whether better outpatient care might prevent some of these readmissions, the researchers said. To explore these questions, they used the Medicare-linked U.S. Health and Retirement Study to study hospitalization codes that indicated sepsis – that is, both acute infection and organ dysfunction. They also compared survivors of severe sepsis with patients who were discharged after hospitalization for 15 other common conditions.

Severe sepsis did not seem to increase the likelihood of rehospitalization – about 42% of both groups of patients were readmitted within 90 days, Dr. Prescott and her associates said. However, ACSCs such as heart failure, pneumonia, worsening chronic obstructive pulmonary disease, and urinary tract infections accounted for about 42% of 90-day readmissions among sepsis survivors (95% confidence interval, 39.2% to 44.1%), versus 37% of the comparison group (95% confidence interval, 34.8%-39.5%; P = .009).

Further, survivors of severe sepsis (12%; 95% confidence interval, 10.6%-13.1%) were more likely than other patients (8%; 95% CI, 7.0%-9.1%; P < .001) to be readmitted with another primary infection, including sepsis, pneumonia, urinary tract infections, and skin and soft tissue infections.

“A limitation of the present study is that we inferred the potential preventability of re-hospitalizations by measuring readmissions for ACSCs,” the researchers noted. “Whether these diagnoses represent preventable admissions, especially after sepsis, is not clear.”

The National Institutes of Health and the Department of Veterans Affairs Health Services Research & Development Service funded the study. The authors reported having no relevant conflicts of interest.

Almost 42% of patients who survived severe sepsis and were rehospitalized within 90 days had conditions for which appropriate outpatient care can potentially prevent readmissions, investigators wrote online March 10 in a letter to JAMA.

These “ambulatory care sensitive conditions” (or ACSCs) accounted for significantly more readmissions among sepsis survivors, compared with patients whose initial hospitalizations were for other reasons, said Dr. Hallie Prescott of the University of Michigan, Ann Arbor, and her associates.

The findings support exploring “the feasibility and potential benefit of post-discharge interventions that are tailored to patients’ personalized risk for a limited number of common conditions,” the investigators said (JAMA 2015;313:1055-7).Patients who survive severe sepsis are often rehospitalized soon afterward, but fairly little is known about the reasons for rehospitalization or whether better outpatient care might prevent some of these readmissions, the researchers said. To explore these questions, they used the Medicare-linked U.S. Health and Retirement Study to study hospitalization codes that indicated sepsis – that is, both acute infection and organ dysfunction. They also compared survivors of severe sepsis with patients who were discharged after hospitalization for 15 other common conditions.

Severe sepsis did not seem to increase the likelihood of rehospitalization – about 42% of both groups of patients were readmitted within 90 days, Dr. Prescott and her associates said. However, ACSCs such as heart failure, pneumonia, worsening chronic obstructive pulmonary disease, and urinary tract infections accounted for about 42% of 90-day readmissions among sepsis survivors (95% confidence interval, 39.2% to 44.1%), versus 37% of the comparison group (95% confidence interval, 34.8%-39.5%; P = .009).

Further, survivors of severe sepsis (12%; 95% confidence interval, 10.6%-13.1%) were more likely than other patients (8%; 95% CI, 7.0%-9.1%; P < .001) to be readmitted with another primary infection, including sepsis, pneumonia, urinary tract infections, and skin and soft tissue infections.

“A limitation of the present study is that we inferred the potential preventability of re-hospitalizations by measuring readmissions for ACSCs,” the researchers noted. “Whether these diagnoses represent preventable admissions, especially after sepsis, is not clear.”

The National Institutes of Health and the Department of Veterans Affairs Health Services Research & Development Service funded the study. The authors reported having no relevant conflicts of interest.

A genetic assay designed to predict breast cancer metastasis and response to adjuvant chemotherapy has undergone rapid uptake, and clinicians are generally following guidelines for its use, researchers reported online in JAMA Oncology.

Overall use of the Oncotype DX 21-gene recurrence score (RS) assay rose from 1.1% in 2005 to 10.1% in 2009 (P < .001), reported Dr. Michaela Dinan of Duke University, Durham, N.C., and her associates.

©ktsimage/Thinkstock.com

“We found that use of the assay was largely restricted to the populations for which it was initially approved in 2005, namely women with estrogen receptor-positive, lymph node-negative, stage I or II breast cancer,” the investigators said (JAMA Oncol. 2015 Mar. 5 [doi:10.1001/jamaoncol.2015.43]).The RS assay has been available commercially since 2004, and the Centers for Medicare & Medicaid Services has covered it since 2006. Dr. Dinan and her associates studied records from a Surveillance, Epidemiology and End Results (SEER) data set with linked Medicare claims to understand trends in testing. The study included 70,802 patients with breast cancer, all of whom were at least 66 years old at diagnosis.

Almost 61% of patients who were tested with the RS assay met the National Comprehensive Cancer Network’s criteria for intermediate-risk disease – estrogen receptor–positive, lymph node–negative tumors measuring more than 1 cm, said the researchers. Most other tested patients had “borderline” indications for use of the assay, such as T1b or N1 disease. Significant predictors of testing included being less than 70 years old at diagnosis, having less than two comorbid conditions, and having tumors that were grade 2 or 3 or larger than 2 cm. Testing varied little geographically, and not at all by race, the investigators noted.

The RS assay is currently not required or universally recommended for all breast cancer patients who are considering adjuvant chemotherapy, so the researchers could not assess whether patients were being adequately tested, they said. They recommended analyzing other data besides that from the SEER-Medicare data set, including data on younger women, who might have distinct patterns of testing and chemotherapy use. Because some studies also indicated that the RS assay might be useful in patients with node-positive disease, the investigators also suggested examining its use in this setting and assessing how testing affects costs, chemotherapy use, and treatment outcomes.

The Agency for Healthcare Research and Quality funded the study. The authors reporting having no relevant conflicts of interest.

A genetic assay designed to predict breast cancer metastasis and response to adjuvant chemotherapy has undergone rapid uptake, and clinicians are generally following guidelines for its use, researchers reported online in JAMA Oncology.

Overall use of the Oncotype DX 21-gene recurrence score (RS) assay rose from 1.1% in 2005 to 10.1% in 2009 (P < .001), reported Dr. Michaela Dinan of Duke University, Durham, N.C., and her associates.

©ktsimage/Thinkstock.com

“We found that use of the assay was largely restricted to the populations for which it was initially approved in 2005, namely women with estrogen receptor-positive, lymph node-negative, stage I or II breast cancer,” the investigators said (JAMA Oncol. 2015 Mar. 5 [doi:10.1001/jamaoncol.2015.43]).The RS assay has been available commercially since 2004, and the Centers for Medicare & Medicaid Services has covered it since 2006. Dr. Dinan and her associates studied records from a Surveillance, Epidemiology and End Results (SEER) data set with linked Medicare claims to understand trends in testing. The study included 70,802 patients with breast cancer, all of whom were at least 66 years old at diagnosis.

Almost 61% of patients who were tested with the RS assay met the National Comprehensive Cancer Network’s criteria for intermediate-risk disease – estrogen receptor–positive, lymph node–negative tumors measuring more than 1 cm, said the researchers. Most other tested patients had “borderline” indications for use of the assay, such as T1b or N1 disease. Significant predictors of testing included being less than 70 years old at diagnosis, having less than two comorbid conditions, and having tumors that were grade 2 or 3 or larger than 2 cm. Testing varied little geographically, and not at all by race, the investigators noted.

The RS assay is currently not required or universally recommended for all breast cancer patients who are considering adjuvant chemotherapy, so the researchers could not assess whether patients were being adequately tested, they said. They recommended analyzing other data besides that from the SEER-Medicare data set, including data on younger women, who might have distinct patterns of testing and chemotherapy use. Because some studies also indicated that the RS assay might be useful in patients with node-positive disease, the investigators also suggested examining its use in this setting and assessing how testing affects costs, chemotherapy use, and treatment outcomes.

The Agency for Healthcare Research and Quality funded the study. The authors reporting having no relevant conflicts of interest.

A genetic assay designed to predict breast cancer metastasis and response to adjuvant chemotherapy has undergone rapid uptake, and clinicians are generally following guidelines for its use, researchers reported online in JAMA Oncology.

Overall use of the Oncotype DX 21-gene recurrence score (RS) assay rose from 1.1% in 2005 to 10.1% in 2009 (P < .001), reported Dr. Michaela Dinan of Duke University, Durham, N.C., and her associates.

©ktsimage/Thinkstock.com

“We found that use of the assay was largely restricted to the populations for which it was initially approved in 2005, namely women with estrogen receptor-positive, lymph node-negative, stage I or II breast cancer,” the investigators said (JAMA Oncol. 2015 Mar. 5 [doi:10.1001/jamaoncol.2015.43]).The RS assay has been available commercially since 2004, and the Centers for Medicare & Medicaid Services has covered it since 2006. Dr. Dinan and her associates studied records from a Surveillance, Epidemiology and End Results (SEER) data set with linked Medicare claims to understand trends in testing. The study included 70,802 patients with breast cancer, all of whom were at least 66 years old at diagnosis.

Almost 61% of patients who were tested with the RS assay met the National Comprehensive Cancer Network’s criteria for intermediate-risk disease – estrogen receptor–positive, lymph node–negative tumors measuring more than 1 cm, said the researchers. Most other tested patients had “borderline” indications for use of the assay, such as T1b or N1 disease. Significant predictors of testing included being less than 70 years old at diagnosis, having less than two comorbid conditions, and having tumors that were grade 2 or 3 or larger than 2 cm. Testing varied little geographically, and not at all by race, the investigators noted.

The RS assay is currently not required or universally recommended for all breast cancer patients who are considering adjuvant chemotherapy, so the researchers could not assess whether patients were being adequately tested, they said. They recommended analyzing other data besides that from the SEER-Medicare data set, including data on younger women, who might have distinct patterns of testing and chemotherapy use. Because some studies also indicated that the RS assay might be useful in patients with node-positive disease, the investigators also suggested examining its use in this setting and assessing how testing affects costs, chemotherapy use, and treatment outcomes.

The Agency for Healthcare Research and Quality funded the study. The authors reporting having no relevant conflicts of interest.

U.S. adults with eczema reported significantly more out-of-pocket health care costs, lost workdays, and comorbid conditions than did their peers without eczema, according to a population-based study reported online March 4 in JAMA Dermatology.

Adult eczema patients also used significantly more health care resources than did adults without eczema, despite reporting more problems accessing care, said Dr. Jonathan I. Silverberg at Northwestern University in Chicago.

About 10.2% of U.S. adults have eczema (atopic dermatitis), but not much is known about its recent direct and indirect health care costs. To explore these questions, Dr. Silverberg analyzed data from the 2010 and 2012 National Health Interview Surveys, which included 27,157 and 34,613 adults, respectively (JAMA Dermatol. 2015 [doi:10.1001/jamadermatol.2014.5432]).

Eczema was linked to 53% higher odds of losing six or more workdays for any reason (odds ratio, 1.53; 95% confidence interval, 1.26-1.84), and with significantly higher odds of visits to physicians’ offices, emergency departments, urgent care centers, and hospitals for all causes, Dr. Silverberg reported. Adults with eczema also paid an estimated $371 to $489 more in out-of-pocket health care costs per year, compared with other adults, he added. “This study demonstrates that adults with eczema have a major health burden with significantly increased health care utilization and costs,” he emphasized.But greater utilization of care “was only partially due to eczema per se,” Dr. Silverberg noted. “There is likely a multitude of comorbid disorders associated with eczema that contributes toward the increased utilization, aside from EAH [eczema with allergy and/or hay fever], or food allergy,” he said. “Indeed, there were significant statistical interactions, such that adults with EAH had even greater burden of disease, out-of-pocket costs, and health care utilization.”

Past studies have shown that children with eczema have more extracutaneous infections, dental disease, and mental health problems, compared with peers who do not have eczema, Dr. Silverberg pointed out, adding that future studies should explore the clinical and financial implications of comorbidities in eczema patients.Eczema also was associated with impaired access to care, Dr. Silverberg said. Affected adults were significantly more likely to describe problems paying for prescriptions (OR, 2.36; 95% CI, 1.92-2.81), getting timely appointments (OR, 2.04; 95% CI, 1.73-2.41), and obtaining care because of worry about costs (OR, 1.66; 95% CI, 1.40-1.97), compared with adults without eczema, Dr. Silverberg said. “Future studies are needed to identify the determinants of health care utilization and access in adults with eczema,” he concluded.

The Agency for Healthcare Research and Quality funded the study. Dr. Silverberg reported having no relevant conflicts of interest.

U.S. adults with eczema reported significantly more out-of-pocket health care costs, lost workdays, and comorbid conditions than did their peers without eczema, according to a population-based study reported online March 4 in JAMA Dermatology.

Adult eczema patients also used significantly more health care resources than did adults without eczema, despite reporting more problems accessing care, said Dr. Jonathan I. Silverberg at Northwestern University in Chicago.

About 10.2% of U.S. adults have eczema (atopic dermatitis), but not much is known about its recent direct and indirect health care costs. To explore these questions, Dr. Silverberg analyzed data from the 2010 and 2012 National Health Interview Surveys, which included 27,157 and 34,613 adults, respectively (JAMA Dermatol. 2015 [doi:10.1001/jamadermatol.2014.5432]).

Eczema was linked to 53% higher odds of losing six or more workdays for any reason (odds ratio, 1.53; 95% confidence interval, 1.26-1.84), and with significantly higher odds of visits to physicians’ offices, emergency departments, urgent care centers, and hospitals for all causes, Dr. Silverberg reported. Adults with eczema also paid an estimated $371 to $489 more in out-of-pocket health care costs per year, compared with other adults, he added. “This study demonstrates that adults with eczema have a major health burden with significantly increased health care utilization and costs,” he emphasized.But greater utilization of care “was only partially due to eczema per se,” Dr. Silverberg noted. “There is likely a multitude of comorbid disorders associated with eczema that contributes toward the increased utilization, aside from EAH [eczema with allergy and/or hay fever], or food allergy,” he said. “Indeed, there were significant statistical interactions, such that adults with EAH had even greater burden of disease, out-of-pocket costs, and health care utilization.”

Past studies have shown that children with eczema have more extracutaneous infections, dental disease, and mental health problems, compared with peers who do not have eczema, Dr. Silverberg pointed out, adding that future studies should explore the clinical and financial implications of comorbidities in eczema patients.Eczema also was associated with impaired access to care, Dr. Silverberg said. Affected adults were significantly more likely to describe problems paying for prescriptions (OR, 2.36; 95% CI, 1.92-2.81), getting timely appointments (OR, 2.04; 95% CI, 1.73-2.41), and obtaining care because of worry about costs (OR, 1.66; 95% CI, 1.40-1.97), compared with adults without eczema, Dr. Silverberg said. “Future studies are needed to identify the determinants of health care utilization and access in adults with eczema,” he concluded.

The Agency for Healthcare Research and Quality funded the study. Dr. Silverberg reported having no relevant conflicts of interest.

U.S. adults with eczema reported significantly more out-of-pocket health care costs, lost workdays, and comorbid conditions than did their peers without eczema, according to a population-based study reported online March 4 in JAMA Dermatology.

Adult eczema patients also used significantly more health care resources than did adults without eczema, despite reporting more problems accessing care, said Dr. Jonathan I. Silverberg at Northwestern University in Chicago.

About 10.2% of U.S. adults have eczema (atopic dermatitis), but not much is known about its recent direct and indirect health care costs. To explore these questions, Dr. Silverberg analyzed data from the 2010 and 2012 National Health Interview Surveys, which included 27,157 and 34,613 adults, respectively (JAMA Dermatol. 2015 [doi:10.1001/jamadermatol.2014.5432]).

Eczema was linked to 53% higher odds of losing six or more workdays for any reason (odds ratio, 1.53; 95% confidence interval, 1.26-1.84), and with significantly higher odds of visits to physicians’ offices, emergency departments, urgent care centers, and hospitals for all causes, Dr. Silverberg reported. Adults with eczema also paid an estimated $371 to $489 more in out-of-pocket health care costs per year, compared with other adults, he added. “This study demonstrates that adults with eczema have a major health burden with significantly increased health care utilization and costs,” he emphasized.But greater utilization of care “was only partially due to eczema per se,” Dr. Silverberg noted. “There is likely a multitude of comorbid disorders associated with eczema that contributes toward the increased utilization, aside from EAH [eczema with allergy and/or hay fever], or food allergy,” he said. “Indeed, there were significant statistical interactions, such that adults with EAH had even greater burden of disease, out-of-pocket costs, and health care utilization.”

Past studies have shown that children with eczema have more extracutaneous infections, dental disease, and mental health problems, compared with peers who do not have eczema, Dr. Silverberg pointed out, adding that future studies should explore the clinical and financial implications of comorbidities in eczema patients.Eczema also was associated with impaired access to care, Dr. Silverberg said. Affected adults were significantly more likely to describe problems paying for prescriptions (OR, 2.36; 95% CI, 1.92-2.81), getting timely appointments (OR, 2.04; 95% CI, 1.73-2.41), and obtaining care because of worry about costs (OR, 1.66; 95% CI, 1.40-1.97), compared with adults without eczema, Dr. Silverberg said. “Future studies are needed to identify the determinants of health care utilization and access in adults with eczema,” he concluded.

The Agency for Healthcare Research and Quality funded the study. Dr. Silverberg reported having no relevant conflicts of interest.

During 5 years of follow-up, cancer arose in only 0.3% of thyroid nodules that were cytologically and sonographically benign at baseline, according to a large prospective study published online March 3 in JAMA.

Furthermore, only two of the five nodules that became cancerous had grown beforehand, reported Dr. Cosimo Durante of the Sapienza University of Rome and his associates. “These data suggest that the American Thyroid Association’s recommendation for indication for repeat cytology should be revised. Clinical and sonographic findings should probably play larger roles in the decision-making process,” the researchers said (JAMA 2015;313:926-35).

Advances in diagnostic imaging have increased the detection of thyroid nodules, the great majority of which are found to be benign. For such nodules, the ATA recommends repeating thyroid ultrasonography at 6-18 months and then every 3-5 years thereafter, as long as nodules do not significantly grow (defined as at least a 20% increase in two nodule diameters, with a minimum increase of at least 2 mm [Thyroid 2009;19:1167-214]). But little is known about rate, extent, or predictors of nodule growth, the researchers noted. Therefore, they performed annual thyroid ultrasound examinations on 992 patients who had one to four asymptomatic subcentimeter thyroid modules that were cytologically or sonographically benign at baseline.

After 5 years of follow-up, just 15.4% of patients had experienced significant nodule growth according to the ATA definition, the researchers reported. Average growth was 4.9 mm, and 9.3% of patients developed new nodules, of which one was found to be cancerous. Growth was least likely when a patient’s largest nodule measured 7.5 mm or less and was significantly more likely when patients had multiple nodules instead of one; had baseline nodule volume greater than 0.2 mL; were up to 45 years old, compared with at least 60 years of age; and were male, the investigators said.

Among older patients, having a body mass index of 28.6 kg/m² more than doubled the odds of nodule growth, in keeping with recent reports linking obesity and insulin resistance with nodular thyroid disease, they added.

The findings suggest that repeat thyroid ultrasonography could be safely extended to 12 months for initial follow-up and to every 5 years thereafter for most patients, as long as nodule size remained stable, Dr. Durante and his associates said. “This approach should be suitable for about 85% of patients, whose risk of disease progression is low. Closer surveillance may be appropriate for nodules occurring in younger patients or older overweight individuals with multiple nodules, large nodules (greater than 7.5 mm), or both,” they added.

The Umberto Di Mario Foundation, Banca d’Italia, and the Italian Thyroid Cancer Observatory Foundation funded the study. The authors reported having no conflicts of interest.

During 5 years of follow-up, cancer arose in only 0.3% of thyroid nodules that were cytologically and sonographically benign at baseline, according to a large prospective study published online March 3 in JAMA.

Furthermore, only two of the five nodules that became cancerous had grown beforehand, reported Dr. Cosimo Durante of the Sapienza University of Rome and his associates. “These data suggest that the American Thyroid Association’s recommendation for indication for repeat cytology should be revised. Clinical and sonographic findings should probably play larger roles in the decision-making process,” the researchers said (JAMA 2015;313:926-35).

Advances in diagnostic imaging have increased the detection of thyroid nodules, the great majority of which are found to be benign. For such nodules, the ATA recommends repeating thyroid ultrasonography at 6-18 months and then every 3-5 years thereafter, as long as nodules do not significantly grow (defined as at least a 20% increase in two nodule diameters, with a minimum increase of at least 2 mm [Thyroid 2009;19:1167-214]). But little is known about rate, extent, or predictors of nodule growth, the researchers noted. Therefore, they performed annual thyroid ultrasound examinations on 992 patients who had one to four asymptomatic subcentimeter thyroid modules that were cytologically or sonographically benign at baseline.

After 5 years of follow-up, just 15.4% of patients had experienced significant nodule growth according to the ATA definition, the researchers reported. Average growth was 4.9 mm, and 9.3% of patients developed new nodules, of which one was found to be cancerous. Growth was least likely when a patient’s largest nodule measured 7.5 mm or less and was significantly more likely when patients had multiple nodules instead of one; had baseline nodule volume greater than 0.2 mL; were up to 45 years old, compared with at least 60 years of age; and were male, the investigators said.

Among older patients, having a body mass index of 28.6 kg/m² more than doubled the odds of nodule growth, in keeping with recent reports linking obesity and insulin resistance with nodular thyroid disease, they added.

The findings suggest that repeat thyroid ultrasonography could be safely extended to 12 months for initial follow-up and to every 5 years thereafter for most patients, as long as nodule size remained stable, Dr. Durante and his associates said. “This approach should be suitable for about 85% of patients, whose risk of disease progression is low. Closer surveillance may be appropriate for nodules occurring in younger patients or older overweight individuals with multiple nodules, large nodules (greater than 7.5 mm), or both,” they added.

The Umberto Di Mario Foundation, Banca d’Italia, and the Italian Thyroid Cancer Observatory Foundation funded the study. The authors reported having no conflicts of interest.

During 5 years of follow-up, cancer arose in only 0.3% of thyroid nodules that were cytologically and sonographically benign at baseline, according to a large prospective study published online March 3 in JAMA.

Furthermore, only two of the five nodules that became cancerous had grown beforehand, reported Dr. Cosimo Durante of the Sapienza University of Rome and his associates. “These data suggest that the American Thyroid Association’s recommendation for indication for repeat cytology should be revised. Clinical and sonographic findings should probably play larger roles in the decision-making process,” the researchers said (JAMA 2015;313:926-35).

Advances in diagnostic imaging have increased the detection of thyroid nodules, the great majority of which are found to be benign. For such nodules, the ATA recommends repeating thyroid ultrasonography at 6-18 months and then every 3-5 years thereafter, as long as nodules do not significantly grow (defined as at least a 20% increase in two nodule diameters, with a minimum increase of at least 2 mm [Thyroid 2009;19:1167-214]). But little is known about rate, extent, or predictors of nodule growth, the researchers noted. Therefore, they performed annual thyroid ultrasound examinations on 992 patients who had one to four asymptomatic subcentimeter thyroid modules that were cytologically or sonographically benign at baseline.

After 5 years of follow-up, just 15.4% of patients had experienced significant nodule growth according to the ATA definition, the researchers reported. Average growth was 4.9 mm, and 9.3% of patients developed new nodules, of which one was found to be cancerous. Growth was least likely when a patient’s largest nodule measured 7.5 mm or less and was significantly more likely when patients had multiple nodules instead of one; had baseline nodule volume greater than 0.2 mL; were up to 45 years old, compared with at least 60 years of age; and were male, the investigators said.

Among older patients, having a body mass index of 28.6 kg/m² more than doubled the odds of nodule growth, in keeping with recent reports linking obesity and insulin resistance with nodular thyroid disease, they added.

The findings suggest that repeat thyroid ultrasonography could be safely extended to 12 months for initial follow-up and to every 5 years thereafter for most patients, as long as nodule size remained stable, Dr. Durante and his associates said. “This approach should be suitable for about 85% of patients, whose risk of disease progression is low. Closer surveillance may be appropriate for nodules occurring in younger patients or older overweight individuals with multiple nodules, large nodules (greater than 7.5 mm), or both,” they added.

The Umberto Di Mario Foundation, Banca d’Italia, and the Italian Thyroid Cancer Observatory Foundation funded the study. The authors reported having no conflicts of interest.

During 5 years of follow-up, cancer arose in only 0.3% of thyroid nodules that were cytologically and sonographically benign at baseline, according to a large prospective study published online March 3 in JAMA.

Furthermore, only two of the five nodules that became cancerous had grown beforehand, reported Dr. Cosimo Durante of the Sapienza University of Rome and his associates. “These data suggest that the American Thyroid Association’s recommendation for indication for repeat cytology should be revised. Clinical and sonographic findings should probably play larger roles in the decision-making process,” the researchers said (JAMA 2015;313:926-35).

©Sebastian Kaulitzki/Fotolia.com

Advances in diagnostic imaging have increased the detection of thyroid nodules, the great majority of which are found to be benign. For such nodules, the ATA recommends repeating thyroid ultrasonography at 6-18 months and then every 3-5 years thereafter, as long as nodules do not significantly grow (defined as at least a 20% increase in two nodule diameters, with a minimum increase of at least 2 mm [Thyroid 2009;19:1167-214]). But little is known about rate, extent, or predictors of nodule growth, the researchers noted. Therefore, they performed annual thyroid ultrasound examinations on 992 patients who had one to four asymptomatic subcentimeter thyroid modules that were cytologically or sonographically benign at baseline.

After 5 years of follow-up, just 15.4% of patients had experienced significant nodule growth according to the ATA definition, the researchers reported. Average growth was 4.9 mm, and 9.3% of patients developed new nodules, of which one was found to be cancerous. Growth was least likely when a patient’s largest nodule measured 7.5 mm or less and was significantly more likely when patients had multiple nodules instead of one; had baseline nodule volume greater than 0.2 mL; were up to 45 years old, compared with at least 60 years of age; and were male, the investigators said.

Among older patients, having a body mass index of 28.6 kg/m² more than doubled the odds of nodule growth, in keeping with recent reports linking obesity and insulin resistance with nodular thyroid disease, they added.

The findings suggest that repeat thyroid ultrasonography could be safely extended to 12 months for initial follow-up and to every 5 years thereafter for most patients, as long as nodule size remained stable, Dr. Durante and his associates said. “This approach should be suitable for about 85% of patients, whose risk of disease progression is low. Closer surveillance may be appropriate for nodules occurring in younger patients or older overweight individuals with multiple nodules, large nodules (greater than 7.5 mm), or both,” they added.

The Umberto Di Mario Foundation, Banca d’Italia, and the Italian Thyroid Cancer Observatory Foundation funded the study. The authors reported having no conflicts of interest.

During 5 years of follow-up, cancer arose in only 0.3% of thyroid nodules that were cytologically and sonographically benign at baseline, according to a large prospective study published online March 3 in JAMA.

Furthermore, only two of the five nodules that became cancerous had grown beforehand, reported Dr. Cosimo Durante of the Sapienza University of Rome and his associates. “These data suggest that the American Thyroid Association’s recommendation for indication for repeat cytology should be revised. Clinical and sonographic findings should probably play larger roles in the decision-making process,” the researchers said (JAMA 2015;313:926-35).

©Sebastian Kaulitzki/Fotolia.com

Advances in diagnostic imaging have increased the detection of thyroid nodules, the great majority of which are found to be benign. For such nodules, the ATA recommends repeating thyroid ultrasonography at 6-18 months and then every 3-5 years thereafter, as long as nodules do not significantly grow (defined as at least a 20% increase in two nodule diameters, with a minimum increase of at least 2 mm [Thyroid 2009;19:1167-214]). But little is known about rate, extent, or predictors of nodule growth, the researchers noted. Therefore, they performed annual thyroid ultrasound examinations on 992 patients who had one to four asymptomatic subcentimeter thyroid modules that were cytologically or sonographically benign at baseline.

After 5 years of follow-up, just 15.4% of patients had experienced significant nodule growth according to the ATA definition, the researchers reported. Average growth was 4.9 mm, and 9.3% of patients developed new nodules, of which one was found to be cancerous. Growth was least likely when a patient’s largest nodule measured 7.5 mm or less and was significantly more likely when patients had multiple nodules instead of one; had baseline nodule volume greater than 0.2 mL; were up to 45 years old, compared with at least 60 years of age; and were male, the investigators said.

Among older patients, having a body mass index of 28.6 kg/m² more than doubled the odds of nodule growth, in keeping with recent reports linking obesity and insulin resistance with nodular thyroid disease, they added.

The findings suggest that repeat thyroid ultrasonography could be safely extended to 12 months for initial follow-up and to every 5 years thereafter for most patients, as long as nodule size remained stable, Dr. Durante and his associates said. “This approach should be suitable for about 85% of patients, whose risk of disease progression is low. Closer surveillance may be appropriate for nodules occurring in younger patients or older overweight individuals with multiple nodules, large nodules (greater than 7.5 mm), or both,” they added.

The Umberto Di Mario Foundation, Banca d’Italia, and the Italian Thyroid Cancer Observatory Foundation funded the study. The authors reported having no conflicts of interest.

During 5 years of follow-up, cancer arose in only 0.3% of thyroid nodules that were cytologically and sonographically benign at baseline, according to a large prospective study published online March 3 in JAMA.

Furthermore, only two of the five nodules that became cancerous had grown beforehand, reported Dr. Cosimo Durante of the Sapienza University of Rome and his associates. “These data suggest that the American Thyroid Association’s recommendation for indication for repeat cytology should be revised. Clinical and sonographic findings should probably play larger roles in the decision-making process,” the researchers said (JAMA 2015;313:926-35).

©Sebastian Kaulitzki/Fotolia.com

Advances in diagnostic imaging have increased the detection of thyroid nodules, the great majority of which are found to be benign. For such nodules, the ATA recommends repeating thyroid ultrasonography at 6-18 months and then every 3-5 years thereafter, as long as nodules do not significantly grow (defined as at least a 20% increase in two nodule diameters, with a minimum increase of at least 2 mm [Thyroid 2009;19:1167-214]). But little is known about rate, extent, or predictors of nodule growth, the researchers noted. Therefore, they performed annual thyroid ultrasound examinations on 992 patients who had one to four asymptomatic subcentimeter thyroid modules that were cytologically or sonographically benign at baseline.

After 5 years of follow-up, just 15.4% of patients had experienced significant nodule growth according to the ATA definition, the researchers reported. Average growth was 4.9 mm, and 9.3% of patients developed new nodules, of which one was found to be cancerous. Growth was least likely when a patient’s largest nodule measured 7.5 mm or less and was significantly more likely when patients had multiple nodules instead of one; had baseline nodule volume greater than 0.2 mL; were up to 45 years old, compared with at least 60 years of age; and were male, the investigators said.

Among older patients, having a body mass index of 28.6 kg/m² more than doubled the odds of nodule growth, in keeping with recent reports linking obesity and insulin resistance with nodular thyroid disease, they added.

The findings suggest that repeat thyroid ultrasonography could be safely extended to 12 months for initial follow-up and to every 5 years thereafter for most patients, as long as nodule size remained stable, Dr. Durante and his associates said. “This approach should be suitable for about 85% of patients, whose risk of disease progression is low. Closer surveillance may be appropriate for nodules occurring in younger patients or older overweight individuals with multiple nodules, large nodules (greater than 7.5 mm), or both,” they added.

The Umberto Di Mario Foundation, Banca d’Italia, and the Italian Thyroid Cancer Observatory Foundation funded the study. The authors reported having no conflicts of interest.

Infliximab caused liver injury in 8.3% of treated patients in a prospective study, exceeding rates for other tumor necrosis factor-alpha antagonists, investigators reported online in Clinical Gastroenterology and Hepatology.

The findings show that “liver injury associated with the use of TNF-alpha antagonists is more common than previously reported, occurring in 1 in 120 of those exposed to infliximab,” said Dr. Einar S. Björnsson at the University of Iceland in Reykjavik and his associates. Furthermore, neither anti-TNF treatment dose nor baseline antinuclear acid antibody (ANA) status predicted which patients would develop drug-induced liver injury (DILI), the researchers said.

Since emerging in the 1990s, anti-TNF agents have dramatically altered the treatment landscape for autoimmune diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Although they are known to cause liver damage in some patients, data on the topic mainly come from single case reports, the researchers said (Clin. Gastroenterol. Hepatol. 2014 [doi: http://dx.doi.org/10.1016/j.cgh.2014.07.062]) To better understand the association, the researchers prospectively studied patients who received anti-TNF agents between 2009 and 2013 at the University Hospital in Iceland. They defined liver injury as aspartate aminotransferase or alanine aminotransferase (ALT) levels that were at least triple the normal upper limit, or alkaline phosphatase levels of at least double the upper limit.

A total of 1,776 patients were treated with anti-TNF agents during the 5-year study period, the researchers reported. In all, 11 developed drug-induced liver injury (DILI), of which nine cases were caused by infliximab, they said. Liver injury developed in 8.3% of patients treated with infliximab, compared with only 3.7% of those who received adalimumab and 2.3% of those given etanercept, they added. In a past analysis, the researchers calculated that one in every 148 patients would develop DILI during 2 years of treatment with infliximab (Gastroenterology 2014;144:1419-25). Patients who developed DILI on one anti-TNF agent were able to switch therapies without DILI recurring, the investigators said. Seven patients were switched from infliximab to adalimumab, etanercept, or both, and one was switched to infliximab after developing DILI on adalimumab, they added.

The researchers also compared the 11 cases to 22 randomized controls matched by age, sex, underlying condition, and treatment. Notably, among the 11 patients diagnosed with DILI, just 1 (9%) was receiving methotrexate at the time of diagnosis, compared with 59% of the controls (P = .009), they reported. “The reason for this is not clear,” they added. “Methotrexate has been shown to lead to a decrease in circulating autoantibodies in cutaneous lupus erythematosus, but the influence of methotrexate could not be confirmed during infliximab treatment.”

Five of the 11 patients with DILI had liver biopsies, of which three showed severe acute hepatitis, two indicated mild unspecified chronic hepatitis, and one showed pure canalicular cholestasis, the researchers reported. About half the patients needed steroids acutely, but “the vast majority” did not need long-term steroid treatment, they said. Exactly how anti-TNF agents cause liver injury remains unclear, they added. Future studies might evaluate whether these drugs trigger CD4 T cells to react against liver cells, as is the case in classic autoimmune hepatitis, they said.

The researchers reported no funding sources and declared having no conflicts of interest.

Infliximab caused liver injury in 8.3% of treated patients in a prospective study, exceeding rates for other tumor necrosis factor-alpha antagonists, investigators reported online in Clinical Gastroenterology and Hepatology.

The findings show that “liver injury associated with the use of TNF-alpha antagonists is more common than previously reported, occurring in 1 in 120 of those exposed to infliximab,” said Dr. Einar S. Björnsson at the University of Iceland in Reykjavik and his associates. Furthermore, neither anti-TNF treatment dose nor baseline antinuclear acid antibody (ANA) status predicted which patients would develop drug-induced liver injury (DILI), the researchers said.

Since emerging in the 1990s, anti-TNF agents have dramatically altered the treatment landscape for autoimmune diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Although they are known to cause liver damage in some patients, data on the topic mainly come from single case reports, the researchers said (Clin. Gastroenterol. Hepatol. 2014 [doi: http://dx.doi.org/10.1016/j.cgh.2014.07.062]) To better understand the association, the researchers prospectively studied patients who received anti-TNF agents between 2009 and 2013 at the University Hospital in Iceland. They defined liver injury as aspartate aminotransferase or alanine aminotransferase (ALT) levels that were at least triple the normal upper limit, or alkaline phosphatase levels of at least double the upper limit.

A total of 1,776 patients were treated with anti-TNF agents during the 5-year study period, the researchers reported. In all, 11 developed drug-induced liver injury (DILI), of which nine cases were caused by infliximab, they said. Liver injury developed in 8.3% of patients treated with infliximab, compared with only 3.7% of those who received adalimumab and 2.3% of those given etanercept, they added. In a past analysis, the researchers calculated that one in every 148 patients would develop DILI during 2 years of treatment with infliximab (Gastroenterology 2014;144:1419-25). Patients who developed DILI on one anti-TNF agent were able to switch therapies without DILI recurring, the investigators said. Seven patients were switched from infliximab to adalimumab, etanercept, or both, and one was switched to infliximab after developing DILI on adalimumab, they added.

The researchers also compared the 11 cases to 22 randomized controls matched by age, sex, underlying condition, and treatment. Notably, among the 11 patients diagnosed with DILI, just 1 (9%) was receiving methotrexate at the time of diagnosis, compared with 59% of the controls (P = .009), they reported. “The reason for this is not clear,” they added. “Methotrexate has been shown to lead to a decrease in circulating autoantibodies in cutaneous lupus erythematosus, but the influence of methotrexate could not be confirmed during infliximab treatment.”

Five of the 11 patients with DILI had liver biopsies, of which three showed severe acute hepatitis, two indicated mild unspecified chronic hepatitis, and one showed pure canalicular cholestasis, the researchers reported. About half the patients needed steroids acutely, but “the vast majority” did not need long-term steroid treatment, they said. Exactly how anti-TNF agents cause liver injury remains unclear, they added. Future studies might evaluate whether these drugs trigger CD4 T cells to react against liver cells, as is the case in classic autoimmune hepatitis, they said.

The researchers reported no funding sources and declared having no conflicts of interest.

Infliximab caused liver injury in 8.3% of treated patients in a prospective study, exceeding rates for other tumor necrosis factor-alpha antagonists, investigators reported online in Clinical Gastroenterology and Hepatology.

The findings show that “liver injury associated with the use of TNF-alpha antagonists is more common than previously reported, occurring in 1 in 120 of those exposed to infliximab,” said Dr. Einar S. Björnsson at the University of Iceland in Reykjavik and his associates. Furthermore, neither anti-TNF treatment dose nor baseline antinuclear acid antibody (ANA) status predicted which patients would develop drug-induced liver injury (DILI), the researchers said.

Since emerging in the 1990s, anti-TNF agents have dramatically altered the treatment landscape for autoimmune diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Although they are known to cause liver damage in some patients, data on the topic mainly come from single case reports, the researchers said (Clin. Gastroenterol. Hepatol. 2014 [doi: http://dx.doi.org/10.1016/j.cgh.2014.07.062]) To better understand the association, the researchers prospectively studied patients who received anti-TNF agents between 2009 and 2013 at the University Hospital in Iceland. They defined liver injury as aspartate aminotransferase or alanine aminotransferase (ALT) levels that were at least triple the normal upper limit, or alkaline phosphatase levels of at least double the upper limit.

A total of 1,776 patients were treated with anti-TNF agents during the 5-year study period, the researchers reported. In all, 11 developed drug-induced liver injury (DILI), of which nine cases were caused by infliximab, they said. Liver injury developed in 8.3% of patients treated with infliximab, compared with only 3.7% of those who received adalimumab and 2.3% of those given etanercept, they added. In a past analysis, the researchers calculated that one in every 148 patients would develop DILI during 2 years of treatment with infliximab (Gastroenterology 2014;144:1419-25). Patients who developed DILI on one anti-TNF agent were able to switch therapies without DILI recurring, the investigators said. Seven patients were switched from infliximab to adalimumab, etanercept, or both, and one was switched to infliximab after developing DILI on adalimumab, they added.

The researchers also compared the 11 cases to 22 randomized controls matched by age, sex, underlying condition, and treatment. Notably, among the 11 patients diagnosed with DILI, just 1 (9%) was receiving methotrexate at the time of diagnosis, compared with 59% of the controls (P = .009), they reported. “The reason for this is not clear,” they added. “Methotrexate has been shown to lead to a decrease in circulating autoantibodies in cutaneous lupus erythematosus, but the influence of methotrexate could not be confirmed during infliximab treatment.”

Five of the 11 patients with DILI had liver biopsies, of which three showed severe acute hepatitis, two indicated mild unspecified chronic hepatitis, and one showed pure canalicular cholestasis, the researchers reported. About half the patients needed steroids acutely, but “the vast majority” did not need long-term steroid treatment, they said. Exactly how anti-TNF agents cause liver injury remains unclear, they added. Future studies might evaluate whether these drugs trigger CD4 T cells to react against liver cells, as is the case in classic autoimmune hepatitis, they said.

The researchers reported no funding sources and declared having no conflicts of interest.

Chronic Helicobacter pylori infection suppresses interleukin-33 cytokine in the stomach, which inhibits the CD4+ T helper cell 2 (or Th2) response and may set the stage for gastric carcinoma, investigators reported online in Cellular and Molecular Gastroenterology and Hepatology.

But long-term rises in IL-33 also can trigger precancerous changes in the stomach by causing the immune system to skew excessively toward Th2 instead of Th1 immunity, said Jon Buzzelli and his associates at the University of Melbourne in Parkville, Australia.

“Despite the immune response being vastly different ... the outcome appears to be similar, as preneoplastic changes occur in both settings,” the researchers added. “In keeping with recent findings, these data suggest that H. pylori may be a beneficial organism that under certain circumstances may help to ensure that gastric immunity is tightly regulated.” (Cellular and Molecular Gastroenterology and Hepatology 2015 [http://dx.doi.org/10.1016/j.jcmgh.2014.12.003 5])

©NDDIC.NIH.gov

IL-33 is a member of a diverse group of cytokines called alarmins, which quickly trigger an immune response to injury or infection when released by dying cells. Fasted mice in the study that were given oral aspirin to induce gastric injury had elevated IL-33 expression, compared with controls 4 hours later, the investigators reported. “This demonstrates that IL-33 responds immediately to gastric insult through relocalization and transcriptional changes, and may be involved in gastric wound healing,” they added.

The researchers also found that gastric IL-33 levels in mice rose fourfold just 1 day after they were infected with H. pylori. But 2 months later, the mice’s IL-33 levels had fallen below those of controls, resembling the researchers’ comparison of H. pylori–positive and uninfected human stomach specimens, they said.

Furthermore, the drop in IL-33 caused a tilt away from Th2 toward Th1 immunity, which appeared to trigger precancerous changes to the gastric mucosa, the researchers added. “The inhibition of gastric IL-33 in response to chronic H. pylori infection may be a key event in gastric cancer progression,” they concluded.

But eliminating H. pylori might also cause problems in some cases, the findings suggested. The declining prevalence of helicobacteriosis in humans has accompanied a rise in Barrett’s esophagus, which precedes esophageal cancer, they noted. When the researchers administered extra IL-33 to mice – mimicking the absence of H. pylori – the cardia of their stomachs expanded and became markedly metaplastic, which precedes Barrett’s esophagus in humans, they noted. H. pylori might help prevent Barrett’s esophagus by suppressing IL-33 and thereby regulating Th2 immunity, they concluded.

The researchers also found that mice born and reared in a pathogen-free environment had lower IL-33 levels, compared with those in conventional housing, they said. Gastric IL-33 expression appeared to rise as bacterial load and diversity increased, supporting the idea that IL-33 functions in this setting as an alarmin, they added.

The investigators also examined whether the TFF2 gene – which helps regulate homeostasis in mucus cells – promoted IL-33 expression in the stomach, as it does in the lungs. Indeed, TFF2 knockout mice had about 40% less gastric IL-33, compared with wild-type mice, they said. Humans with chronic helicobacteriosis also have low TFF2 expression, which continues to fall as gastric cancer grows, they noted.

The study was funded by the Victorian Government’s Operational Infrastructure Support Program and National Health & Medical Research Council, Australia. The researchers reported no conflicts of interest.

Chronic Helicobacter pylori infection suppresses interleukin-33 cytokine in the stomach, which inhibits the CD4+ T helper cell 2 (or Th2) response and may set the stage for gastric carcinoma, investigators reported online in Cellular and Molecular Gastroenterology and Hepatology.

But long-term rises in IL-33 also can trigger precancerous changes in the stomach by causing the immune system to skew excessively toward Th2 instead of Th1 immunity, said Jon Buzzelli and his associates at the University of Melbourne in Parkville, Australia.

“Despite the immune response being vastly different ... the outcome appears to be similar, as preneoplastic changes occur in both settings,” the researchers added. “In keeping with recent findings, these data suggest that H. pylori may be a beneficial organism that under certain circumstances may help to ensure that gastric immunity is tightly regulated.” (Cellular and Molecular Gastroenterology and Hepatology 2015 [http://dx.doi.org/10.1016/j.jcmgh.2014.12.003 5])

©NDDIC.NIH.gov

IL-33 is a member of a diverse group of cytokines called alarmins, which quickly trigger an immune response to injury or infection when released by dying cells. Fasted mice in the study that were given oral aspirin to induce gastric injury had elevated IL-33 expression, compared with controls 4 hours later, the investigators reported. “This demonstrates that IL-33 responds immediately to gastric insult through relocalization and transcriptional changes, and may be involved in gastric wound healing,” they added.

The researchers also found that gastric IL-33 levels in mice rose fourfold just 1 day after they were infected with H. pylori. But 2 months later, the mice’s IL-33 levels had fallen below those of controls, resembling the researchers’ comparison of H. pylori–positive and uninfected human stomach specimens, they said.

Furthermore, the drop in IL-33 caused a tilt away from Th2 toward Th1 immunity, which appeared to trigger precancerous changes to the gastric mucosa, the researchers added. “The inhibition of gastric IL-33 in response to chronic H. pylori infection may be a key event in gastric cancer progression,” they concluded.

But eliminating H. pylori might also cause problems in some cases, the findings suggested. The declining prevalence of helicobacteriosis in humans has accompanied a rise in Barrett’s esophagus, which precedes esophageal cancer, they noted. When the researchers administered extra IL-33 to mice – mimicking the absence of H. pylori – the cardia of their stomachs expanded and became markedly metaplastic, which precedes Barrett’s esophagus in humans, they noted. H. pylori might help prevent Barrett’s esophagus by suppressing IL-33 and thereby regulating Th2 immunity, they concluded.

The researchers also found that mice born and reared in a pathogen-free environment had lower IL-33 levels, compared with those in conventional housing, they said. Gastric IL-33 expression appeared to rise as bacterial load and diversity increased, supporting the idea that IL-33 functions in this setting as an alarmin, they added.

The investigators also examined whether the TFF2 gene – which helps regulate homeostasis in mucus cells – promoted IL-33 expression in the stomach, as it does in the lungs. Indeed, TFF2 knockout mice had about 40% less gastric IL-33, compared with wild-type mice, they said. Humans with chronic helicobacteriosis also have low TFF2 expression, which continues to fall as gastric cancer grows, they noted.

The study was funded by the Victorian Government’s Operational Infrastructure Support Program and National Health & Medical Research Council, Australia. The researchers reported no conflicts of interest.

Chronic Helicobacter pylori infection suppresses interleukin-33 cytokine in the stomach, which inhibits the CD4+ T helper cell 2 (or Th2) response and may set the stage for gastric carcinoma, investigators reported online in Cellular and Molecular Gastroenterology and Hepatology.

But long-term rises in IL-33 also can trigger precancerous changes in the stomach by causing the immune system to skew excessively toward Th2 instead of Th1 immunity, said Jon Buzzelli and his associates at the University of Melbourne in Parkville, Australia.

“Despite the immune response being vastly different ... the outcome appears to be similar, as preneoplastic changes occur in both settings,” the researchers added. “In keeping with recent findings, these data suggest that H. pylori may be a beneficial organism that under certain circumstances may help to ensure that gastric immunity is tightly regulated.” (Cellular and Molecular Gastroenterology and Hepatology 2015 [http://dx.doi.org/10.1016/j.jcmgh.2014.12.003 5])

©NDDIC.NIH.gov

IL-33 is a member of a diverse group of cytokines called alarmins, which quickly trigger an immune response to injury or infection when released by dying cells. Fasted mice in the study that were given oral aspirin to induce gastric injury had elevated IL-33 expression, compared with controls 4 hours later, the investigators reported. “This demonstrates that IL-33 responds immediately to gastric insult through relocalization and transcriptional changes, and may be involved in gastric wound healing,” they added.

The researchers also found that gastric IL-33 levels in mice rose fourfold just 1 day after they were infected with H. pylori. But 2 months later, the mice’s IL-33 levels had fallen below those of controls, resembling the researchers’ comparison of H. pylori–positive and uninfected human stomach specimens, they said.

Furthermore, the drop in IL-33 caused a tilt away from Th2 toward Th1 immunity, which appeared to trigger precancerous changes to the gastric mucosa, the researchers added. “The inhibition of gastric IL-33 in response to chronic H. pylori infection may be a key event in gastric cancer progression,” they concluded.

But eliminating H. pylori might also cause problems in some cases, the findings suggested. The declining prevalence of helicobacteriosis in humans has accompanied a rise in Barrett’s esophagus, which precedes esophageal cancer, they noted. When the researchers administered extra IL-33 to mice – mimicking the absence of H. pylori – the cardia of their stomachs expanded and became markedly metaplastic, which precedes Barrett’s esophagus in humans, they noted. H. pylori might help prevent Barrett’s esophagus by suppressing IL-33 and thereby regulating Th2 immunity, they concluded.

The researchers also found that mice born and reared in a pathogen-free environment had lower IL-33 levels, compared with those in conventional housing, they said. Gastric IL-33 expression appeared to rise as bacterial load and diversity increased, supporting the idea that IL-33 functions in this setting as an alarmin, they added.

The investigators also examined whether the TFF2 gene – which helps regulate homeostasis in mucus cells – promoted IL-33 expression in the stomach, as it does in the lungs. Indeed, TFF2 knockout mice had about 40% less gastric IL-33, compared with wild-type mice, they said. Humans with chronic helicobacteriosis also have low TFF2 expression, which continues to fall as gastric cancer grows, they noted.

The study was funded by the Victorian Government’s Operational Infrastructure Support Program and National Health & Medical Research Council, Australia. The researchers reported no conflicts of interest.

In a registry-based study, 3.8% of patients with pancreatic cancer had germline mutations in genes known to significantly increase cancer risk, researchers reported in the March issue of Gastroenterology.

“A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study shows the value of using a multiple-gene panel in pancreatic cancer,” said Robert Grant of the Ontario Institute for Cancer Research in Toronto and his associates.

©SilverV/Thinkstock.com

Source: American Gastroenterological Association

Some patients had mutations in the BRCA and MMR genes, about which enough is known to help guide preventive measures and treatment decisions, the researchers noted. “Furthermore, all mutation carriers represent a high-risk subgroup of patients for pancreatic cancer researchers to consider for screening studies and for experimental targeted therapies,” the investigators wrote (Gastroenterology 2014 Dec. 2 [doi:10.1053/j.gastro.2014.11.042]).

For the study, the investigators carried out multigene next-generation sequencing of DNA from the blood and saliva of 290 patients with pancreatic cancer. The patients were randomly chosen from a population-based pancreatic cancer registry in Ontario. The researchers looked for mutations in 13 genes that have been previously linked to cancers: APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53. They found a total of 11 pathogenic germline mutations in seven of these genes, including 3 in the ATM gene, 1 in BRCA1,2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53, they reported.

A total of 3.8% (95% confidence interval, 2.1%-5.6%) of the patients carried mutations, or about 1 in every 26 patients, said the researchers. Most mutations were linked to breast or colorectal cancer. Mutation carriers were significantly more likely to have been diagnosed with breast cancer or colorectal cancer themselves, or to have an affected first-degree relative (P < .01 for both), compared with other patients in the study.

Furthermore, the prevalence of mutations jumped to 10.7% (95% CI, 4.4%-11.1%) when the researchers looked only at patients with a personal or family history of breast cancer, and to 11.1% (95% CI, 3.0%-19.1%) in the subgroup of patients with a personal or family history of colorectal cancer, the investigators reported.

But mutation status was not linked with familial pancreatic cancer, nor with age at diagnosis, which “raises questions with important clinical implications,” said the researchers. “With decreasing sequencing costs, which patients should be referred for multiple-gene panel sequencing? What is the relevance of mutations in [patients] with atypical personal and family histories?”

Answering those questions would require studying many genes from large groups of patients with pancreatic cancer, they emphasized. For now, although multiple-gene panels cost about the same amount as single-gene tests, “the added value of simultaneously sequencing many genes remains uncertain, and likely depends on the clinical setting,” they said. Nonetheless, the analysis uncovered so many mutations in the cohort that the researchers would recommend multiple-gene testing of patients with pancreatic cancer, they said.

Patients were recruited into the registry based on pathology results, which would have excluded those with advanced pancreatic cancer who never had pathology testing, said the investigators. Also, study patients tended to be younger, to have been treated in academic centers, and to have resectable disease more often than other patients in Ontario with pancreatic cancer.

The work was funded by the Weston Garfield Foundation, Pancreatic Cancer Canada, National Cancer Institute, Mount Sinai Hospital Biospecimen Repository, and Teresa Bianco. The investigators declared having no conflicts of interest.

In a registry-based study, 3.8% of patients with pancreatic cancer had germline mutations in genes known to significantly increase cancer risk, researchers reported in the March issue of Gastroenterology.

“A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study shows the value of using a multiple-gene panel in pancreatic cancer,” said Robert Grant of the Ontario Institute for Cancer Research in Toronto and his associates.

©SilverV/Thinkstock.com

Source: American Gastroenterological Association

Some patients had mutations in the BRCA and MMR genes, about which enough is known to help guide preventive measures and treatment decisions, the researchers noted. “Furthermore, all mutation carriers represent a high-risk subgroup of patients for pancreatic cancer researchers to consider for screening studies and for experimental targeted therapies,” the investigators wrote (Gastroenterology 2014 Dec. 2 [doi:10.1053/j.gastro.2014.11.042]).

For the study, the investigators carried out multigene next-generation sequencing of DNA from the blood and saliva of 290 patients with pancreatic cancer. The patients were randomly chosen from a population-based pancreatic cancer registry in Ontario. The researchers looked for mutations in 13 genes that have been previously linked to cancers: APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53. They found a total of 11 pathogenic germline mutations in seven of these genes, including 3 in the ATM gene, 1 in BRCA1,2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53, they reported.

A total of 3.8% (95% confidence interval, 2.1%-5.6%) of the patients carried mutations, or about 1 in every 26 patients, said the researchers. Most mutations were linked to breast or colorectal cancer. Mutation carriers were significantly more likely to have been diagnosed with breast cancer or colorectal cancer themselves, or to have an affected first-degree relative (P < .01 for both), compared with other patients in the study.

Furthermore, the prevalence of mutations jumped to 10.7% (95% CI, 4.4%-11.1%) when the researchers looked only at patients with a personal or family history of breast cancer, and to 11.1% (95% CI, 3.0%-19.1%) in the subgroup of patients with a personal or family history of colorectal cancer, the investigators reported.

But mutation status was not linked with familial pancreatic cancer, nor with age at diagnosis, which “raises questions with important clinical implications,” said the researchers. “With decreasing sequencing costs, which patients should be referred for multiple-gene panel sequencing? What is the relevance of mutations in [patients] with atypical personal and family histories?”

Answering those questions would require studying many genes from large groups of patients with pancreatic cancer, they emphasized. For now, although multiple-gene panels cost about the same amount as single-gene tests, “the added value of simultaneously sequencing many genes remains uncertain, and likely depends on the clinical setting,” they said. Nonetheless, the analysis uncovered so many mutations in the cohort that the researchers would recommend multiple-gene testing of patients with pancreatic cancer, they said.

Patients were recruited into the registry based on pathology results, which would have excluded those with advanced pancreatic cancer who never had pathology testing, said the investigators. Also, study patients tended to be younger, to have been treated in academic centers, and to have resectable disease more often than other patients in Ontario with pancreatic cancer.

The work was funded by the Weston Garfield Foundation, Pancreatic Cancer Canada, National Cancer Institute, Mount Sinai Hospital Biospecimen Repository, and Teresa Bianco. The investigators declared having no conflicts of interest.

In a registry-based study, 3.8% of patients with pancreatic cancer had germline mutations in genes known to significantly increase cancer risk, researchers reported in the March issue of Gastroenterology.

“A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study shows the value of using a multiple-gene panel in pancreatic cancer,” said Robert Grant of the Ontario Institute for Cancer Research in Toronto and his associates.

©SilverV/Thinkstock.com

Source: American Gastroenterological Association

Some patients had mutations in the BRCA and MMR genes, about which enough is known to help guide preventive measures and treatment decisions, the researchers noted. “Furthermore, all mutation carriers represent a high-risk subgroup of patients for pancreatic cancer researchers to consider for screening studies and for experimental targeted therapies,” the investigators wrote (Gastroenterology 2014 Dec. 2 [doi:10.1053/j.gastro.2014.11.042]).

For the study, the investigators carried out multigene next-generation sequencing of DNA from the blood and saliva of 290 patients with pancreatic cancer. The patients were randomly chosen from a population-based pancreatic cancer registry in Ontario. The researchers looked for mutations in 13 genes that have been previously linked to cancers: APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53. They found a total of 11 pathogenic germline mutations in seven of these genes, including 3 in the ATM gene, 1 in BRCA1,2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53, they reported.

A total of 3.8% (95% confidence interval, 2.1%-5.6%) of the patients carried mutations, or about 1 in every 26 patients, said the researchers. Most mutations were linked to breast or colorectal cancer. Mutation carriers were significantly more likely to have been diagnosed with breast cancer or colorectal cancer themselves, or to have an affected first-degree relative (P < .01 for both), compared with other patients in the study.

Furthermore, the prevalence of mutations jumped to 10.7% (95% CI, 4.4%-11.1%) when the researchers looked only at patients with a personal or family history of breast cancer, and to 11.1% (95% CI, 3.0%-19.1%) in the subgroup of patients with a personal or family history of colorectal cancer, the investigators reported.

But mutation status was not linked with familial pancreatic cancer, nor with age at diagnosis, which “raises questions with important clinical implications,” said the researchers. “With decreasing sequencing costs, which patients should be referred for multiple-gene panel sequencing? What is the relevance of mutations in [patients] with atypical personal and family histories?”

Answering those questions would require studying many genes from large groups of patients with pancreatic cancer, they emphasized. For now, although multiple-gene panels cost about the same amount as single-gene tests, “the added value of simultaneously sequencing many genes remains uncertain, and likely depends on the clinical setting,” they said. Nonetheless, the analysis uncovered so many mutations in the cohort that the researchers would recommend multiple-gene testing of patients with pancreatic cancer, they said.

Patients were recruited into the registry based on pathology results, which would have excluded those with advanced pancreatic cancer who never had pathology testing, said the investigators. Also, study patients tended to be younger, to have been treated in academic centers, and to have resectable disease more often than other patients in Ontario with pancreatic cancer.

The work was funded by the Weston Garfield Foundation, Pancreatic Cancer Canada, National Cancer Institute, Mount Sinai Hospital Biospecimen Repository, and Teresa Bianco. The investigators declared having no conflicts of interest.