Older patients with ccRCC may respond better than younger patients to phosphoinositide 3-kinase (PI3K) or checkpoint inhibition because of age-related changes in gene expression, according to investigators.

This possibility was raised by in silico results from a broader study of gene expression patterns in clear cell renal carcinoma (ccRCC) and normal kidney tissues, reported lead author, Lara Feulner, MD, of the department of human genetics at McGill University and Genome Quebec Innovation Centre in Montreal.

“Several factors could contribute to the interindividual diversity among cancer patients,” the investigators wrote in a report published in Urologic Oncology.

“Their disease course could be affected not only by cell-intrinsic factors, but also by age-related changes impacting the vasculature, immune system and stroma. Little is known in this regard about ccRCC, a disease which affects adults across a wide age spectrum. Whether and how aging and comorbidities such as atherosclerosis may affect the biology and therapy of ccRCC has scarcely been considered,” they wrote.

The investigators explored this territory by analyzing datasets from The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) program of the International Cancer Genome Consortium. Using regression, pathway enrichment, and connectivity mapping analyses, they were able to determine associations between age and gene expression, cellular processes, and drug treatment responses, respectively.

The investigators reported that age-related gene expression patterns occurred commonly in both normal and tumor tissues. Associations were reproducible between TCGA and CAGEKID datasets for both classes of tissue (tumor samples, R equal to 0.416, P less than 2.2 x 10-16; normal samples, R equal to 0.403, P less than 2.2 x 10-16). Out of the top 1,000 age-associated genes in tumor samples from each dataset, 383 were commonly downregulated with age and 294 were commonly upregulated with age in both datasets (P less than 2.2 x 10-16).

Among cellular pathways, the investigators found opposite age-relationship patterns. For example, normal tissues upregulated extracellular matrix and cell adhesion pathways with age, whereas tumor tissues downregulated the same pathways. Similar patterns of opposition were found in metabolism and oxidation pathways. Other age-related patterns were noted in some immune pathways, such as upregulation of toll-like receptor and tumor necrosis factor 2 noncanonical NF-kappa-B signaling in tumors, which became more common with age. A closer look showed that upregulation of tumor necrosis factor signaling was more common in female patients, who also downregulated Notch pathways more often than men.

Analysis of treatment responses showed possible relationships with age-dependent gene expression and immunotherapy. Specifically, of 532 genes tied to programmed cell death protein 1 (PD-1) resistance, 69 were among the 383 genes downregulated in older patients with ccRCC (P less than 2.2 x 10-16; 4.05 fold-enrichment), suggesting that older patients may respond better to anti-PD-1 therapy than younger patients. Similarly, connectivity map analysis showed that age-dependent gene expression may improve candidacy of older ccRCC patients for PI3K inhibition.

“We now have evidence that there are notable differences in tumor-associated pathway regulation between younger and older ccRCC patients, which may be therapeutically actionable,” the authors concluded.

The study was funded by the Cancer Research Society operation grant, a Canadian Cancer Society Research Institute Innovation-to-Impact grant, and a Canadian Institutes of Health Research Foundation grant. The authors reported no conflicts of interest.

SOURCE: Feulner et al. Urol Onc. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.11.006.

Older patients with ccRCC may respond better than younger patients to phosphoinositide 3-kinase (PI3K) or checkpoint inhibition because of age-related changes in gene expression, according to investigators.

This possibility was raised by in silico results from a broader study of gene expression patterns in clear cell renal carcinoma (ccRCC) and normal kidney tissues, reported lead author, Lara Feulner, MD, of the department of human genetics at McGill University and Genome Quebec Innovation Centre in Montreal.

“Several factors could contribute to the interindividual diversity among cancer patients,” the investigators wrote in a report published in Urologic Oncology.

“Their disease course could be affected not only by cell-intrinsic factors, but also by age-related changes impacting the vasculature, immune system and stroma. Little is known in this regard about ccRCC, a disease which affects adults across a wide age spectrum. Whether and how aging and comorbidities such as atherosclerosis may affect the biology and therapy of ccRCC has scarcely been considered,” they wrote.

The investigators explored this territory by analyzing datasets from The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) program of the International Cancer Genome Consortium. Using regression, pathway enrichment, and connectivity mapping analyses, they were able to determine associations between age and gene expression, cellular processes, and drug treatment responses, respectively.

The investigators reported that age-related gene expression patterns occurred commonly in both normal and tumor tissues. Associations were reproducible between TCGA and CAGEKID datasets for both classes of tissue (tumor samples, R equal to 0.416, P less than 2.2 x 10-16; normal samples, R equal to 0.403, P less than 2.2 x 10-16). Out of the top 1,000 age-associated genes in tumor samples from each dataset, 383 were commonly downregulated with age and 294 were commonly upregulated with age in both datasets (P less than 2.2 x 10-16).

Among cellular pathways, the investigators found opposite age-relationship patterns. For example, normal tissues upregulated extracellular matrix and cell adhesion pathways with age, whereas tumor tissues downregulated the same pathways. Similar patterns of opposition were found in metabolism and oxidation pathways. Other age-related patterns were noted in some immune pathways, such as upregulation of toll-like receptor and tumor necrosis factor 2 noncanonical NF-kappa-B signaling in tumors, which became more common with age. A closer look showed that upregulation of tumor necrosis factor signaling was more common in female patients, who also downregulated Notch pathways more often than men.

Analysis of treatment responses showed possible relationships with age-dependent gene expression and immunotherapy. Specifically, of 532 genes tied to programmed cell death protein 1 (PD-1) resistance, 69 were among the 383 genes downregulated in older patients with ccRCC (P less than 2.2 x 10-16; 4.05 fold-enrichment), suggesting that older patients may respond better to anti-PD-1 therapy than younger patients. Similarly, connectivity map analysis showed that age-dependent gene expression may improve candidacy of older ccRCC patients for PI3K inhibition.

“We now have evidence that there are notable differences in tumor-associated pathway regulation between younger and older ccRCC patients, which may be therapeutically actionable,” the authors concluded.

The study was funded by the Cancer Research Society operation grant, a Canadian Cancer Society Research Institute Innovation-to-Impact grant, and a Canadian Institutes of Health Research Foundation grant. The authors reported no conflicts of interest.

SOURCE: Feulner et al. Urol Onc. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.11.006.

Older patients with ccRCC may respond better than younger patients to phosphoinositide 3-kinase (PI3K) or checkpoint inhibition because of age-related changes in gene expression, according to investigators.

This possibility was raised by in silico results from a broader study of gene expression patterns in clear cell renal carcinoma (ccRCC) and normal kidney tissues, reported lead author, Lara Feulner, MD, of the department of human genetics at McGill University and Genome Quebec Innovation Centre in Montreal.

“Several factors could contribute to the interindividual diversity among cancer patients,” the investigators wrote in a report published in Urologic Oncology.

“Their disease course could be affected not only by cell-intrinsic factors, but also by age-related changes impacting the vasculature, immune system and stroma. Little is known in this regard about ccRCC, a disease which affects adults across a wide age spectrum. Whether and how aging and comorbidities such as atherosclerosis may affect the biology and therapy of ccRCC has scarcely been considered,” they wrote.

The investigators explored this territory by analyzing datasets from The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) program of the International Cancer Genome Consortium. Using regression, pathway enrichment, and connectivity mapping analyses, they were able to determine associations between age and gene expression, cellular processes, and drug treatment responses, respectively.

The investigators reported that age-related gene expression patterns occurred commonly in both normal and tumor tissues. Associations were reproducible between TCGA and CAGEKID datasets for both classes of tissue (tumor samples, R equal to 0.416, P less than 2.2 x 10-16; normal samples, R equal to 0.403, P less than 2.2 x 10-16). Out of the top 1,000 age-associated genes in tumor samples from each dataset, 383 were commonly downregulated with age and 294 were commonly upregulated with age in both datasets (P less than 2.2 x 10-16).

Among cellular pathways, the investigators found opposite age-relationship patterns. For example, normal tissues upregulated extracellular matrix and cell adhesion pathways with age, whereas tumor tissues downregulated the same pathways. Similar patterns of opposition were found in metabolism and oxidation pathways. Other age-related patterns were noted in some immune pathways, such as upregulation of toll-like receptor and tumor necrosis factor 2 noncanonical NF-kappa-B signaling in tumors, which became more common with age. A closer look showed that upregulation of tumor necrosis factor signaling was more common in female patients, who also downregulated Notch pathways more often than men.

Analysis of treatment responses showed possible relationships with age-dependent gene expression and immunotherapy. Specifically, of 532 genes tied to programmed cell death protein 1 (PD-1) resistance, 69 were among the 383 genes downregulated in older patients with ccRCC (P less than 2.2 x 10-16; 4.05 fold-enrichment), suggesting that older patients may respond better to anti-PD-1 therapy than younger patients. Similarly, connectivity map analysis showed that age-dependent gene expression may improve candidacy of older ccRCC patients for PI3K inhibition.

“We now have evidence that there are notable differences in tumor-associated pathway regulation between younger and older ccRCC patients, which may be therapeutically actionable,” the authors concluded.

The study was funded by the Cancer Research Society operation grant, a Canadian Cancer Society Research Institute Innovation-to-Impact grant, and a Canadian Institutes of Health Research Foundation grant. The authors reported no conflicts of interest.

SOURCE: Feulner et al. Urol Onc. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.11.006.

San Diego – In patients with atrial fibrillation who had direct oral anticoagulant (DOAC) interruption for an elective surgery, a simple and standardized management strategy yielded low rates of bleeding and thromboembolism, according to results of a prospective study of more than 3,000 patients.

Rates of major bleeding were less than 2% and rates of arterial thromboembolism were less than 1% in patients managed in accordance with the strategy, which foregoes heparin bridging and preoperative coagulation testing, according to investigator James D. Douketis, MD, of St. Joseph’s Healthcare and McMaster University, Hamilton, Ont.

“This is the first study to demonstrate the safety of a standardized perioperative management approach in a patients with atrial fibrillation who are taking a DOAC, and we hope will establish a standard and will have an effect on our clinical practice guidelines,” Dr. Douketis said during a press briefing at the annual meeting of the American Society of Hematology.

This trial offers the “most definitive evidence to date” that atrial fibrillation patients can – in an organized fashion based on bleeding risk – safely stop taking DOACs, said Mark Crowther, MD, chair and professor of medicine at McMaster University.

“This study will almost instantaneously establish a treatment practice and a treatment standard for the vast number of patients in North America and around the world who take these drugs,” added Dr. Crowther, who moderated the press briefing.

The PAUSE study included three parallel cohorts of atrial fibrillation patients taking DOACs (apixaban, dabigatran, or rivaroxaban) who required anticoagulant interruption for an elective surgery or procedure.

The DOAC interruptions were done using standardized protocols based on the pharmacokinetic properties of each DOAC, procedure-associated bleeding risk, and creatinine clearance, the investigators reported.

The interruptions occurred 1 day before and after low bleeding risk surgeries, and 2 days before and after high bleeding risk surgeries, while longer interruptions were used in patients receiving dabigatran who had a creatinine clearance below 50 mL/min.

A total of 3,007 patients at 23 sites in Canada, the United States, and Europe were managed by this approach in the PAUSE study – 1,257 patients receiving apixaban, 668 receiving dabigatran, and 1,082 receiving rivaroxaban – and were evaluated weekly for 30 days post-procedure.

PAUSE is the largest study to date that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care.

The 30-day postoperative rate of major bleeding was low, according to investigators, at 1.35% (95% confidence interval, 0-2.00%) for apixaban, 0.90% (95% CI, 0-1.73%) for dabigatran, and 1.85% (95% CI, 0-2.65%) for rivaroxaban, Dr. Douketis reported.

Likewise, the rate of arterial thromboembolism was low at 0.16% (95% CI, 0-0.48%) for apixaban, 0.6% (95% CI, 0-1.33%) for dabigatran, and 0.37% (95% CI, 0-0.82%) for rivaroxaban, he said.

Most patients (greater than 90%) had minimal to no residual DOAC levels at the time of surgery, the investigator added.

The study was funded by the Canadian Institutes of Health Research and the H&S Foundation of Canada. Dr. Douketis reported disclosures related to Janssen, which makes rivaroxaban; Boehringer-Ingelheim, which makes dabigatran; and other companies. Dr. Crowther reported financial relationships with Bristol-Myers Squibb and other companies.

SOURCE: Douketis J et al. ASH 2018, Abstract LBA-5.

San Diego – In patients with atrial fibrillation who had direct oral anticoagulant (DOAC) interruption for an elective surgery, a simple and standardized management strategy yielded low rates of bleeding and thromboembolism, according to results of a prospective study of more than 3,000 patients.

Rates of major bleeding were less than 2% and rates of arterial thromboembolism were less than 1% in patients managed in accordance with the strategy, which foregoes heparin bridging and preoperative coagulation testing, according to investigator James D. Douketis, MD, of St. Joseph’s Healthcare and McMaster University, Hamilton, Ont.

“This is the first study to demonstrate the safety of a standardized perioperative management approach in a patients with atrial fibrillation who are taking a DOAC, and we hope will establish a standard and will have an effect on our clinical practice guidelines,” Dr. Douketis said during a press briefing at the annual meeting of the American Society of Hematology.

This trial offers the “most definitive evidence to date” that atrial fibrillation patients can – in an organized fashion based on bleeding risk – safely stop taking DOACs, said Mark Crowther, MD, chair and professor of medicine at McMaster University.

“This study will almost instantaneously establish a treatment practice and a treatment standard for the vast number of patients in North America and around the world who take these drugs,” added Dr. Crowther, who moderated the press briefing.

The PAUSE study included three parallel cohorts of atrial fibrillation patients taking DOACs (apixaban, dabigatran, or rivaroxaban) who required anticoagulant interruption for an elective surgery or procedure.

The DOAC interruptions were done using standardized protocols based on the pharmacokinetic properties of each DOAC, procedure-associated bleeding risk, and creatinine clearance, the investigators reported.

The interruptions occurred 1 day before and after low bleeding risk surgeries, and 2 days before and after high bleeding risk surgeries, while longer interruptions were used in patients receiving dabigatran who had a creatinine clearance below 50 mL/min.

A total of 3,007 patients at 23 sites in Canada, the United States, and Europe were managed by this approach in the PAUSE study – 1,257 patients receiving apixaban, 668 receiving dabigatran, and 1,082 receiving rivaroxaban – and were evaluated weekly for 30 days post-procedure.

PAUSE is the largest study to date that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care.

The 30-day postoperative rate of major bleeding was low, according to investigators, at 1.35% (95% confidence interval, 0-2.00%) for apixaban, 0.90% (95% CI, 0-1.73%) for dabigatran, and 1.85% (95% CI, 0-2.65%) for rivaroxaban, Dr. Douketis reported.

Likewise, the rate of arterial thromboembolism was low at 0.16% (95% CI, 0-0.48%) for apixaban, 0.6% (95% CI, 0-1.33%) for dabigatran, and 0.37% (95% CI, 0-0.82%) for rivaroxaban, he said.

Most patients (greater than 90%) had minimal to no residual DOAC levels at the time of surgery, the investigator added.

The study was funded by the Canadian Institutes of Health Research and the H&S Foundation of Canada. Dr. Douketis reported disclosures related to Janssen, which makes rivaroxaban; Boehringer-Ingelheim, which makes dabigatran; and other companies. Dr. Crowther reported financial relationships with Bristol-Myers Squibb and other companies.

SOURCE: Douketis J et al. ASH 2018, Abstract LBA-5.

San Diego – In patients with atrial fibrillation who had direct oral anticoagulant (DOAC) interruption for an elective surgery, a simple and standardized management strategy yielded low rates of bleeding and thromboembolism, according to results of a prospective study of more than 3,000 patients.

Rates of major bleeding were less than 2% and rates of arterial thromboembolism were less than 1% in patients managed in accordance with the strategy, which foregoes heparin bridging and preoperative coagulation testing, according to investigator James D. Douketis, MD, of St. Joseph’s Healthcare and McMaster University, Hamilton, Ont.

“This is the first study to demonstrate the safety of a standardized perioperative management approach in a patients with atrial fibrillation who are taking a DOAC, and we hope will establish a standard and will have an effect on our clinical practice guidelines,” Dr. Douketis said during a press briefing at the annual meeting of the American Society of Hematology.

This trial offers the “most definitive evidence to date” that atrial fibrillation patients can – in an organized fashion based on bleeding risk – safely stop taking DOACs, said Mark Crowther, MD, chair and professor of medicine at McMaster University.

“This study will almost instantaneously establish a treatment practice and a treatment standard for the vast number of patients in North America and around the world who take these drugs,” added Dr. Crowther, who moderated the press briefing.

The PAUSE study included three parallel cohorts of atrial fibrillation patients taking DOACs (apixaban, dabigatran, or rivaroxaban) who required anticoagulant interruption for an elective surgery or procedure.

The DOAC interruptions were done using standardized protocols based on the pharmacokinetic properties of each DOAC, procedure-associated bleeding risk, and creatinine clearance, the investigators reported.

The interruptions occurred 1 day before and after low bleeding risk surgeries, and 2 days before and after high bleeding risk surgeries, while longer interruptions were used in patients receiving dabigatran who had a creatinine clearance below 50 mL/min.

A total of 3,007 patients at 23 sites in Canada, the United States, and Europe were managed by this approach in the PAUSE study – 1,257 patients receiving apixaban, 668 receiving dabigatran, and 1,082 receiving rivaroxaban – and were evaluated weekly for 30 days post-procedure.

PAUSE is the largest study to date that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care.

The 30-day postoperative rate of major bleeding was low, according to investigators, at 1.35% (95% confidence interval, 0-2.00%) for apixaban, 0.90% (95% CI, 0-1.73%) for dabigatran, and 1.85% (95% CI, 0-2.65%) for rivaroxaban, Dr. Douketis reported.

Likewise, the rate of arterial thromboembolism was low at 0.16% (95% CI, 0-0.48%) for apixaban, 0.6% (95% CI, 0-1.33%) for dabigatran, and 0.37% (95% CI, 0-0.82%) for rivaroxaban, he said.

Most patients (greater than 90%) had minimal to no residual DOAC levels at the time of surgery, the investigator added.

The study was funded by the Canadian Institutes of Health Research and the H&S Foundation of Canada. Dr. Douketis reported disclosures related to Janssen, which makes rivaroxaban; Boehringer-Ingelheim, which makes dabigatran; and other companies. Dr. Crowther reported financial relationships with Bristol-Myers Squibb and other companies.

SOURCE: Douketis J et al. ASH 2018, Abstract LBA-5.

Clear cell renal cell carcinoma (ccRCC) with predominant papillary features is best classified as a rare morphologic variant of ccRCC, not MiT family translocation or papillary RCC, according to an analysis of 23 tumors.

Areas of papillary pattern made up anywhere from 40% to 100% of the 23 tumors. Even so, cytology and immunohistochemical and genetic testing was most consistent with ccRCC, and tumors were negative for TFE3 protein, which ruled out MiT family translocation RCC, reported Reza Alaghehbandan, MD, and his associates. The report is in Annals of Diagnostic Pathology.

The findings help clarify where ccRCC fits in the diagnostic tree when there’s significant papillary morphology, something that hasn’t been clear until now. The proper classification matters because it carries treatment implications; for instance, ccRCC generally responds well to immunotherapy and targeted therapy, but papillary RCC does not, so doctors often recommend treatment through a clinical trial.

“The presence of mixed morphologic components in renal neoplasms in general and in ccRCCs in particular can be puzzling in routine practice, which can potentially lead to misdiagnosis.” Getting it right is “crucial” to ensure the best treatment, said Dr. Alaghehbandan, of the University of British Columbia, Vancouver, and his associates.

Cytokeratin 7 (CK7) staining was negative in the nonpapillary areas of 20 tumors (87%), and only focally positive in three (13%). In contrast, clear cell papillary RCC is strongly and diffusely positive for CK7.

In papillary areas, Alpha-methyl CoA racemase was positive or focally positive in 17 tumors (73.9%); in nonpapillary areas, it was positive or focally positive in 22 (95.6%). Carbonic anhydrase IX was mainly negative in both nonpapillary and papillary areas, while vimentin and CD10 were positive or focally positive in both.

Patients were a mean of 65.2 years old, and 19 were men. The median tumor size was 6.5 cm. At a median follow-up of 2.5 years, two patients had died of their disease, and two had developed metastasis.

There was no industry funding, and the investigators didn’t have any disclosures.

SOURCE: Alaghehbandan R et al. Ann Diagn Pathol. 2018 Nov 22. doi: 10.1016/j.anndiagpath.2018.11.004.

Clear cell renal cell carcinoma (ccRCC) with predominant papillary features is best classified as a rare morphologic variant of ccRCC, not MiT family translocation or papillary RCC, according to an analysis of 23 tumors.

Areas of papillary pattern made up anywhere from 40% to 100% of the 23 tumors. Even so, cytology and immunohistochemical and genetic testing was most consistent with ccRCC, and tumors were negative for TFE3 protein, which ruled out MiT family translocation RCC, reported Reza Alaghehbandan, MD, and his associates. The report is in Annals of Diagnostic Pathology.

The findings help clarify where ccRCC fits in the diagnostic tree when there’s significant papillary morphology, something that hasn’t been clear until now. The proper classification matters because it carries treatment implications; for instance, ccRCC generally responds well to immunotherapy and targeted therapy, but papillary RCC does not, so doctors often recommend treatment through a clinical trial.

“The presence of mixed morphologic components in renal neoplasms in general and in ccRCCs in particular can be puzzling in routine practice, which can potentially lead to misdiagnosis.” Getting it right is “crucial” to ensure the best treatment, said Dr. Alaghehbandan, of the University of British Columbia, Vancouver, and his associates.

Cytokeratin 7 (CK7) staining was negative in the nonpapillary areas of 20 tumors (87%), and only focally positive in three (13%). In contrast, clear cell papillary RCC is strongly and diffusely positive for CK7.

In papillary areas, Alpha-methyl CoA racemase was positive or focally positive in 17 tumors (73.9%); in nonpapillary areas, it was positive or focally positive in 22 (95.6%). Carbonic anhydrase IX was mainly negative in both nonpapillary and papillary areas, while vimentin and CD10 were positive or focally positive in both.

Patients were a mean of 65.2 years old, and 19 were men. The median tumor size was 6.5 cm. At a median follow-up of 2.5 years, two patients had died of their disease, and two had developed metastasis.

There was no industry funding, and the investigators didn’t have any disclosures.

SOURCE: Alaghehbandan R et al. Ann Diagn Pathol. 2018 Nov 22. doi: 10.1016/j.anndiagpath.2018.11.004.

Clear cell renal cell carcinoma (ccRCC) with predominant papillary features is best classified as a rare morphologic variant of ccRCC, not MiT family translocation or papillary RCC, according to an analysis of 23 tumors.

Areas of papillary pattern made up anywhere from 40% to 100% of the 23 tumors. Even so, cytology and immunohistochemical and genetic testing was most consistent with ccRCC, and tumors were negative for TFE3 protein, which ruled out MiT family translocation RCC, reported Reza Alaghehbandan, MD, and his associates. The report is in Annals of Diagnostic Pathology.

The findings help clarify where ccRCC fits in the diagnostic tree when there’s significant papillary morphology, something that hasn’t been clear until now. The proper classification matters because it carries treatment implications; for instance, ccRCC generally responds well to immunotherapy and targeted therapy, but papillary RCC does not, so doctors often recommend treatment through a clinical trial.

“The presence of mixed morphologic components in renal neoplasms in general and in ccRCCs in particular can be puzzling in routine practice, which can potentially lead to misdiagnosis.” Getting it right is “crucial” to ensure the best treatment, said Dr. Alaghehbandan, of the University of British Columbia, Vancouver, and his associates.

Cytokeratin 7 (CK7) staining was negative in the nonpapillary areas of 20 tumors (87%), and only focally positive in three (13%). In contrast, clear cell papillary RCC is strongly and diffusely positive for CK7.

In papillary areas, Alpha-methyl CoA racemase was positive or focally positive in 17 tumors (73.9%); in nonpapillary areas, it was positive or focally positive in 22 (95.6%). Carbonic anhydrase IX was mainly negative in both nonpapillary and papillary areas, while vimentin and CD10 were positive or focally positive in both.

Patients were a mean of 65.2 years old, and 19 were men. The median tumor size was 6.5 cm. At a median follow-up of 2.5 years, two patients had died of their disease, and two had developed metastasis.

There was no industry funding, and the investigators didn’t have any disclosures.

SOURCE: Alaghehbandan R et al. Ann Diagn Pathol. 2018 Nov 22. doi: 10.1016/j.anndiagpath.2018.11.004.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

PHOENIX – An initiative designed to reduce avoidable emergency room visits and hospitalizations cut admissions by 16%, according to a report from a large, independent, community-based oncology practice.

The program saved nearly $3.2 million in Medicare costs over the course of the year, said Molly Mendenhall, RN, of Oncology Hematology Care in Cincinnati.

“By keeping those patients out of the hospital, we were able to improve patient quality of life, and increase patient satisfaction by treating them in their home clinic instead of the hospital,” Ms. Mendenhall said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

The campaign was developed in anticipation of participating in the Oncology Care Model (OCM), a program focused on providing coordinated and high-quality care for Medicare oncology patients at the same or lower cost.

Prior to participating in OCM, Ms. Mendenhall and her colleagues set up an after-hours phone triage system, proactive chemotherapy follow-up calls, and a Saturday-Sunday urgent care clinic designed to help avoid any unnecessary hospitalizations over the weekend.

They also set up a 2-hour structured OCM treatment planning visit to prioritize shared decision making between the patient and the clinical team regarding diagnosis, symptom management, financial assistance, and other aspects of care.

The most influential part of the initiative, according to Ms. Mendenhall, was a patient-directed “Call Us Early – Call Us First” campaign that included symptom management teaching sheets, a 34-page teaching book, and branded buttons, pens, and magnets all designed to emphasize the patient responsibility to use the phone.

“All of those previous steps really wouldn’t make a difference if the patients still weren’t calling us,” Ms. Mendenhall explained.

Over the first year of participation in the OCM program, the oncology practice saw a 16% statistically significant reduction in hospital admissions (P = .005). The number of inpatient admissions per 100 patients dropped from 26.8 at baseline to 22.6 at the most recent follow-up in a report published simultaneously in the Journal of Oncology Practice.

Reduced admissions translated into a drop of $798,000 in inpatient costs per quarter over 1,600 patients, or $3.129 million in savings for the Centers for Medicare & Medicaid Services over the first year of participation in OCM, according to the researchers.

Patient satisfaction scores trended positively over the course of that year based on a review of blinded surveys that asked patients to rate clinical care, communication, access, information exchange, and other aspects of their experience.

Scores on those surveys were 8.03 on a scale of 0-10 (low to high) during the baseline period of January to September 2016, the researchers said. Scores were 8.29 and 8.26 for two follow-up surveys.

Ms. Mendenhall had no disclosures to report. Coauthors on the study provided disclosures related to Janssen Oncology, Pfizer, Amgen, Abbvie, Merck, Pharmacyclics, Bristol-Myers Squibb, Celgene, Genentech/Roche, AZTherapies, and Lilly. Two coauthors reported leadership, stock, or other ownership interests in Oncology Hematology Care/US Oncology.

SOURCE: Mendenhall M et al. Quality Care Symposium, Abstract 30.

PHOENIX – An initiative designed to reduce avoidable emergency room visits and hospitalizations cut admissions by 16%, according to a report from a large, independent, community-based oncology practice.

The program saved nearly $3.2 million in Medicare costs over the course of the year, said Molly Mendenhall, RN, of Oncology Hematology Care in Cincinnati.

“By keeping those patients out of the hospital, we were able to improve patient quality of life, and increase patient satisfaction by treating them in their home clinic instead of the hospital,” Ms. Mendenhall said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

The campaign was developed in anticipation of participating in the Oncology Care Model (OCM), a program focused on providing coordinated and high-quality care for Medicare oncology patients at the same or lower cost.

Prior to participating in OCM, Ms. Mendenhall and her colleagues set up an after-hours phone triage system, proactive chemotherapy follow-up calls, and a Saturday-Sunday urgent care clinic designed to help avoid any unnecessary hospitalizations over the weekend.

They also set up a 2-hour structured OCM treatment planning visit to prioritize shared decision making between the patient and the clinical team regarding diagnosis, symptom management, financial assistance, and other aspects of care.

The most influential part of the initiative, according to Ms. Mendenhall, was a patient-directed “Call Us Early – Call Us First” campaign that included symptom management teaching sheets, a 34-page teaching book, and branded buttons, pens, and magnets all designed to emphasize the patient responsibility to use the phone.

“All of those previous steps really wouldn’t make a difference if the patients still weren’t calling us,” Ms. Mendenhall explained.

Over the first year of participation in the OCM program, the oncology practice saw a 16% statistically significant reduction in hospital admissions (P = .005). The number of inpatient admissions per 100 patients dropped from 26.8 at baseline to 22.6 at the most recent follow-up in a report published simultaneously in the Journal of Oncology Practice.

Reduced admissions translated into a drop of $798,000 in inpatient costs per quarter over 1,600 patients, or $3.129 million in savings for the Centers for Medicare & Medicaid Services over the first year of participation in OCM, according to the researchers.

Patient satisfaction scores trended positively over the course of that year based on a review of blinded surveys that asked patients to rate clinical care, communication, access, information exchange, and other aspects of their experience.

Scores on those surveys were 8.03 on a scale of 0-10 (low to high) during the baseline period of January to September 2016, the researchers said. Scores were 8.29 and 8.26 for two follow-up surveys.

Ms. Mendenhall had no disclosures to report. Coauthors on the study provided disclosures related to Janssen Oncology, Pfizer, Amgen, Abbvie, Merck, Pharmacyclics, Bristol-Myers Squibb, Celgene, Genentech/Roche, AZTherapies, and Lilly. Two coauthors reported leadership, stock, or other ownership interests in Oncology Hematology Care/US Oncology.

SOURCE: Mendenhall M et al. Quality Care Symposium, Abstract 30.

PHOENIX – An initiative designed to reduce avoidable emergency room visits and hospitalizations cut admissions by 16%, according to a report from a large, independent, community-based oncology practice.

The program saved nearly $3.2 million in Medicare costs over the course of the year, said Molly Mendenhall, RN, of Oncology Hematology Care in Cincinnati.

“By keeping those patients out of the hospital, we were able to improve patient quality of life, and increase patient satisfaction by treating them in their home clinic instead of the hospital,” Ms. Mendenhall said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

The campaign was developed in anticipation of participating in the Oncology Care Model (OCM), a program focused on providing coordinated and high-quality care for Medicare oncology patients at the same or lower cost.

Prior to participating in OCM, Ms. Mendenhall and her colleagues set up an after-hours phone triage system, proactive chemotherapy follow-up calls, and a Saturday-Sunday urgent care clinic designed to help avoid any unnecessary hospitalizations over the weekend.

They also set up a 2-hour structured OCM treatment planning visit to prioritize shared decision making between the patient and the clinical team regarding diagnosis, symptom management, financial assistance, and other aspects of care.

The most influential part of the initiative, according to Ms. Mendenhall, was a patient-directed “Call Us Early – Call Us First” campaign that included symptom management teaching sheets, a 34-page teaching book, and branded buttons, pens, and magnets all designed to emphasize the patient responsibility to use the phone.

“All of those previous steps really wouldn’t make a difference if the patients still weren’t calling us,” Ms. Mendenhall explained.

Over the first year of participation in the OCM program, the oncology practice saw a 16% statistically significant reduction in hospital admissions (P = .005). The number of inpatient admissions per 100 patients dropped from 26.8 at baseline to 22.6 at the most recent follow-up in a report published simultaneously in the Journal of Oncology Practice.

Reduced admissions translated into a drop of $798,000 in inpatient costs per quarter over 1,600 patients, or $3.129 million in savings for the Centers for Medicare & Medicaid Services over the first year of participation in OCM, according to the researchers.

Patient satisfaction scores trended positively over the course of that year based on a review of blinded surveys that asked patients to rate clinical care, communication, access, information exchange, and other aspects of their experience.

Scores on those surveys were 8.03 on a scale of 0-10 (low to high) during the baseline period of January to September 2016, the researchers said. Scores were 8.29 and 8.26 for two follow-up surveys.

Ms. Mendenhall had no disclosures to report. Coauthors on the study provided disclosures related to Janssen Oncology, Pfizer, Amgen, Abbvie, Merck, Pharmacyclics, Bristol-Myers Squibb, Celgene, Genentech/Roche, AZTherapies, and Lilly. Two coauthors reported leadership, stock, or other ownership interests in Oncology Hematology Care/US Oncology.

SOURCE: Mendenhall M et al. Quality Care Symposium, Abstract 30.

AUSTIN, TEX. – Using psychological screenings for law enforcement employment decisions can be a worthwhile supplement to more traditional hiring procedures, but such tools should be used with caution, a recent case study suggests.

“Pre-employment psychological evaluations for police officers are increasingly utilizing self-reported personality assessments to identify attributes in candidates that have shown to correlate with job performance outcomes,” Ann Marie Mckenzie Cassidy, DO, of Icahn School of Medicine at Mount Sinai, New York, and her colleagues wrote in an abstract presented at the annual meeting of the American Academy of Psychiatry and the Law.

“As research supporting the predictive power of written self-reported measurements expands, the call for this empirically validated data to be weighted over clinician judgment is becoming more substantive,” the researchers wrote. “The following case exemplifies a psychological evaluation where test results were either inconclusive or strongly conflicted with the clinical picture of the candidate.”

The applicant was a 34-year-old male Army veteran who received an honorable discharge after three deployments. Though he had no relevant medical or formal psychiatric history or drug use, he said he did drink alcohol heavily for a short time after joining the Army. He also had four speeding citations and one drag racing citation.

His personal history revealed several problems, including a military write-up for yelling at a subordinate and a history of difficulties working with his supervisor.

“While working as a car mechanic, he was unable to resolve a conflict with a difficult customer” and quit his job without notice, leading his employer to say he would not hire the applicant again. Yet, the applicant “denied interpersonal issues at work” and said he did not recall the yelling incident. He also said the situation where he quit with only 2 hours’ notice was unfair.

The applicant reported stress, “feeling down and having a diminished interest in activities” following his deployment in Iraq, but he turned down treatment for his stress. He also “used unprofessional language during the examination, and, when asked to refrain from cursing, he did not express concern about this conduct.”

His psychological test results on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), however, suggested “a pattern of positive impression management and defensiveness that is not likely to accurately represent existing psychopathology,” the researchers reported. “Closer review suggests the applicant is apt to see himself as having high moral standards and not having aggressive impulses,” they wrote. Similarly, the applicant’s Sixteen Personality Factor Questionnaire results “reflected an individual who is tough-minded, with low anxiety, who is emotionally stable, deferential, and relaxed.”

These two tools’ findings conflicted with the applicant’s history and presentation, and the examiner deemed him “psychologically unsuitable for hire.”

The researchers said this case reinforces the importance of investigating how empirical data – even with tools such as the MMPI-2, whose predictive power has been validated in several studies – are weighted and used with clinical psychological assessments.

“There needs to be greater feedback about divergent clinical observations and test data before empirically validated test correlates are weighted more heavily,” the researchers concluded. “Until there is greater exploration of divergent or complementary testing findings and clinical judgment, test data should not be weighted over clinical judgment in psychological evaluations.”

AUSTIN, TEX. – Using psychological screenings for law enforcement employment decisions can be a worthwhile supplement to more traditional hiring procedures, but such tools should be used with caution, a recent case study suggests.

“Pre-employment psychological evaluations for police officers are increasingly utilizing self-reported personality assessments to identify attributes in candidates that have shown to correlate with job performance outcomes,” Ann Marie Mckenzie Cassidy, DO, of Icahn School of Medicine at Mount Sinai, New York, and her colleagues wrote in an abstract presented at the annual meeting of the American Academy of Psychiatry and the Law.

“As research supporting the predictive power of written self-reported measurements expands, the call for this empirically validated data to be weighted over clinician judgment is becoming more substantive,” the researchers wrote. “The following case exemplifies a psychological evaluation where test results were either inconclusive or strongly conflicted with the clinical picture of the candidate.”

The applicant was a 34-year-old male Army veteran who received an honorable discharge after three deployments. Though he had no relevant medical or formal psychiatric history or drug use, he said he did drink alcohol heavily for a short time after joining the Army. He also had four speeding citations and one drag racing citation.

His personal history revealed several problems, including a military write-up for yelling at a subordinate and a history of difficulties working with his supervisor.

“While working as a car mechanic, he was unable to resolve a conflict with a difficult customer” and quit his job without notice, leading his employer to say he would not hire the applicant again. Yet, the applicant “denied interpersonal issues at work” and said he did not recall the yelling incident. He also said the situation where he quit with only 2 hours’ notice was unfair.

The applicant reported stress, “feeling down and having a diminished interest in activities” following his deployment in Iraq, but he turned down treatment for his stress. He also “used unprofessional language during the examination, and, when asked to refrain from cursing, he did not express concern about this conduct.”

His psychological test results on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), however, suggested “a pattern of positive impression management and defensiveness that is not likely to accurately represent existing psychopathology,” the researchers reported. “Closer review suggests the applicant is apt to see himself as having high moral standards and not having aggressive impulses,” they wrote. Similarly, the applicant’s Sixteen Personality Factor Questionnaire results “reflected an individual who is tough-minded, with low anxiety, who is emotionally stable, deferential, and relaxed.”

These two tools’ findings conflicted with the applicant’s history and presentation, and the examiner deemed him “psychologically unsuitable for hire.”

The researchers said this case reinforces the importance of investigating how empirical data – even with tools such as the MMPI-2, whose predictive power has been validated in several studies – are weighted and used with clinical psychological assessments.

“There needs to be greater feedback about divergent clinical observations and test data before empirically validated test correlates are weighted more heavily,” the researchers concluded. “Until there is greater exploration of divergent or complementary testing findings and clinical judgment, test data should not be weighted over clinical judgment in psychological evaluations.”

AUSTIN, TEX. – Using psychological screenings for law enforcement employment decisions can be a worthwhile supplement to more traditional hiring procedures, but such tools should be used with caution, a recent case study suggests.

“Pre-employment psychological evaluations for police officers are increasingly utilizing self-reported personality assessments to identify attributes in candidates that have shown to correlate with job performance outcomes,” Ann Marie Mckenzie Cassidy, DO, of Icahn School of Medicine at Mount Sinai, New York, and her colleagues wrote in an abstract presented at the annual meeting of the American Academy of Psychiatry and the Law.

“As research supporting the predictive power of written self-reported measurements expands, the call for this empirically validated data to be weighted over clinician judgment is becoming more substantive,” the researchers wrote. “The following case exemplifies a psychological evaluation where test results were either inconclusive or strongly conflicted with the clinical picture of the candidate.”

The applicant was a 34-year-old male Army veteran who received an honorable discharge after three deployments. Though he had no relevant medical or formal psychiatric history or drug use, he said he did drink alcohol heavily for a short time after joining the Army. He also had four speeding citations and one drag racing citation.

His personal history revealed several problems, including a military write-up for yelling at a subordinate and a history of difficulties working with his supervisor.

“While working as a car mechanic, he was unable to resolve a conflict with a difficult customer” and quit his job without notice, leading his employer to say he would not hire the applicant again. Yet, the applicant “denied interpersonal issues at work” and said he did not recall the yelling incident. He also said the situation where he quit with only 2 hours’ notice was unfair.

The applicant reported stress, “feeling down and having a diminished interest in activities” following his deployment in Iraq, but he turned down treatment for his stress. He also “used unprofessional language during the examination, and, when asked to refrain from cursing, he did not express concern about this conduct.”

His psychological test results on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), however, suggested “a pattern of positive impression management and defensiveness that is not likely to accurately represent existing psychopathology,” the researchers reported. “Closer review suggests the applicant is apt to see himself as having high moral standards and not having aggressive impulses,” they wrote. Similarly, the applicant’s Sixteen Personality Factor Questionnaire results “reflected an individual who is tough-minded, with low anxiety, who is emotionally stable, deferential, and relaxed.”

These two tools’ findings conflicted with the applicant’s history and presentation, and the examiner deemed him “psychologically unsuitable for hire.”

The researchers said this case reinforces the importance of investigating how empirical data – even with tools such as the MMPI-2, whose predictive power has been validated in several studies – are weighted and used with clinical psychological assessments.

“There needs to be greater feedback about divergent clinical observations and test data before empirically validated test correlates are weighted more heavily,” the researchers concluded. “Until there is greater exploration of divergent or complementary testing findings and clinical judgment, test data should not be weighted over clinical judgment in psychological evaluations.”

LAS VEGAS – Injecting the cervix with bupivacaine before laparoscopic hysterectomy significantly reduces postoperative pain, according to a small trial at the University of Tennessee, Chattanooga.

M. Alexander Otto/MDedge News

Twenty-one women were randomized to 0.5% bupivacaine, 5 mL injected into the cervix at the 3 o’clock position, and 5 mL injected into at the 9 o’clock position to a depth of 3 cm, after anesthesia induction but before insertion of the uterine manipulator. A control group of 20 women received 5 mL of 0.9% saline injected into the same positions. Surgeons were blinded to the randomization.

A stopwatch was started at extubation, and the women were asked to rate their pain on a 10-point visual analogue scale exactly at 30 and 60 minutes.

The bupivacaine group had less pain at both 30 minutes (3.2 versus 5.7 points, P = .01) and 60 minutes (2.3 versus 5.9 points, P less than .001); 71% of women in the bupivacaine group had an average score of 4 or less, indicating adequate pain control, versus just 25% in the control arm (P = .003)

“This is something we should be considering” routinely for laparoscopic hysterectomy, an audience member said after hearing the presentation at a meeting sponsored by AAGL.

Another audience member was concerned about urinary retention, but there was no increase in the treatment arm, said lead investigator Steven Radtke, MD, a former ob.gyn. surgery fellow at the university, but now at Texas Tech University, El Paso.

There have been many prior attempts to reduce pain after laparoscopic hysterectomy, such as infiltrating port sites with local anesthetic, but the results have been marginal at best, and almost all of them have focused on the abdominal wall as the source of pain.

The investigators thought that pain was more related to perimetrium dissection, colpotomy, and other parts of the operation. There also have been good studies showing that agents injected into the cervix infuse throughout the area. The team decided to try bupivacaine because it’s inexpensive and has a good duration of action, about 8 hours.

There were no significant demographic or intraoperative differences between the groups. On average, women were in their mid-40s, with a body mass index of about 31 kg/m². The operations took about 2 hours, and were for benign indications, such as fibroids. Oophorectomy was the only concomitant procedure allowed.

The investigators are interested in repeating their investigation with liposomal bupivacaine (Exparel), which has a duration of action past 24 hours. It’s much more expensive, but the strong trial results justify the cost, Dr. Radtke said.

There was no external funding, and Dr. Radtke didn’t have any disclosures.

[email protected]

SOURCE: Radtke S et al. 2018 AAGL Global Congress, Abstract 130.

LAS VEGAS – Injecting the cervix with bupivacaine before laparoscopic hysterectomy significantly reduces postoperative pain, according to a small trial at the University of Tennessee, Chattanooga.

M. Alexander Otto/MDedge News

Twenty-one women were randomized to 0.5% bupivacaine, 5 mL injected into the cervix at the 3 o’clock position, and 5 mL injected into at the 9 o’clock position to a depth of 3 cm, after anesthesia induction but before insertion of the uterine manipulator. A control group of 20 women received 5 mL of 0.9% saline injected into the same positions. Surgeons were blinded to the randomization.

A stopwatch was started at extubation, and the women were asked to rate their pain on a 10-point visual analogue scale exactly at 30 and 60 minutes.

The bupivacaine group had less pain at both 30 minutes (3.2 versus 5.7 points, P = .01) and 60 minutes (2.3 versus 5.9 points, P less than .001); 71% of women in the bupivacaine group had an average score of 4 or less, indicating adequate pain control, versus just 25% in the control arm (P = .003)

“This is something we should be considering” routinely for laparoscopic hysterectomy, an audience member said after hearing the presentation at a meeting sponsored by AAGL.

Another audience member was concerned about urinary retention, but there was no increase in the treatment arm, said lead investigator Steven Radtke, MD, a former ob.gyn. surgery fellow at the university, but now at Texas Tech University, El Paso.

There have been many prior attempts to reduce pain after laparoscopic hysterectomy, such as infiltrating port sites with local anesthetic, but the results have been marginal at best, and almost all of them have focused on the abdominal wall as the source of pain.

The investigators thought that pain was more related to perimetrium dissection, colpotomy, and other parts of the operation. There also have been good studies showing that agents injected into the cervix infuse throughout the area. The team decided to try bupivacaine because it’s inexpensive and has a good duration of action, about 8 hours.

There were no significant demographic or intraoperative differences between the groups. On average, women were in their mid-40s, with a body mass index of about 31 kg/m². The operations took about 2 hours, and were for benign indications, such as fibroids. Oophorectomy was the only concomitant procedure allowed.

The investigators are interested in repeating their investigation with liposomal bupivacaine (Exparel), which has a duration of action past 24 hours. It’s much more expensive, but the strong trial results justify the cost, Dr. Radtke said.

There was no external funding, and Dr. Radtke didn’t have any disclosures.

[email protected]

SOURCE: Radtke S et al. 2018 AAGL Global Congress, Abstract 130.

LAS VEGAS – Injecting the cervix with bupivacaine before laparoscopic hysterectomy significantly reduces postoperative pain, according to a small trial at the University of Tennessee, Chattanooga.

M. Alexander Otto/MDedge News

Twenty-one women were randomized to 0.5% bupivacaine, 5 mL injected into the cervix at the 3 o’clock position, and 5 mL injected into at the 9 o’clock position to a depth of 3 cm, after anesthesia induction but before insertion of the uterine manipulator. A control group of 20 women received 5 mL of 0.9% saline injected into the same positions. Surgeons were blinded to the randomization.

A stopwatch was started at extubation, and the women were asked to rate their pain on a 10-point visual analogue scale exactly at 30 and 60 minutes.

The bupivacaine group had less pain at both 30 minutes (3.2 versus 5.7 points, P = .01) and 60 minutes (2.3 versus 5.9 points, P less than .001); 71% of women in the bupivacaine group had an average score of 4 or less, indicating adequate pain control, versus just 25% in the control arm (P = .003)

“This is something we should be considering” routinely for laparoscopic hysterectomy, an audience member said after hearing the presentation at a meeting sponsored by AAGL.

Another audience member was concerned about urinary retention, but there was no increase in the treatment arm, said lead investigator Steven Radtke, MD, a former ob.gyn. surgery fellow at the university, but now at Texas Tech University, El Paso.

There have been many prior attempts to reduce pain after laparoscopic hysterectomy, such as infiltrating port sites with local anesthetic, but the results have been marginal at best, and almost all of them have focused on the abdominal wall as the source of pain.

The investigators thought that pain was more related to perimetrium dissection, colpotomy, and other parts of the operation. There also have been good studies showing that agents injected into the cervix infuse throughout the area. The team decided to try bupivacaine because it’s inexpensive and has a good duration of action, about 8 hours.

There were no significant demographic or intraoperative differences between the groups. On average, women were in their mid-40s, with a body mass index of about 31 kg/m². The operations took about 2 hours, and were for benign indications, such as fibroids. Oophorectomy was the only concomitant procedure allowed.

The investigators are interested in repeating their investigation with liposomal bupivacaine (Exparel), which has a duration of action past 24 hours. It’s much more expensive, but the strong trial results justify the cost, Dr. Radtke said.

There was no external funding, and Dr. Radtke didn’t have any disclosures.

[email protected]

SOURCE: Radtke S et al. 2018 AAGL Global Congress, Abstract 130.

San Diego – State-of-the-art guidelines for treating sickle cell disease are actively being developed and could be released as early as the spring of 2019, according to Robert Liem, MD, chair of the American Society of Hematology coordination panel for the initiative.

The new clinical practice recommendations will expand on 2014 guidelines published by the National Heart, Lung, and Blood Institute in a way that will help both hematologists and nonhematologists who take care of patients with sickle cell disease, Dr. Liem said in a video interview at the annual meeting of the American Society of Hematology.

Five different guidelines are under development to cover different aspects of acute and chronic complications of sickle cell disease, including pain, cardiopulmonary and kidney disease, cerebrovascular disease, transfusion support, and stem cell transplantation.

Watch the video to learn more about the guideline effort from the perspective of Dr. Liem, who is also the director of the Comprehensive Sickle Cell Program at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

San Diego – State-of-the-art guidelines for treating sickle cell disease are actively being developed and could be released as early as the spring of 2019, according to Robert Liem, MD, chair of the American Society of Hematology coordination panel for the initiative.

The new clinical practice recommendations will expand on 2014 guidelines published by the National Heart, Lung, and Blood Institute in a way that will help both hematologists and nonhematologists who take care of patients with sickle cell disease, Dr. Liem said in a video interview at the annual meeting of the American Society of Hematology.

Five different guidelines are under development to cover different aspects of acute and chronic complications of sickle cell disease, including pain, cardiopulmonary and kidney disease, cerebrovascular disease, transfusion support, and stem cell transplantation.

Watch the video to learn more about the guideline effort from the perspective of Dr. Liem, who is also the director of the Comprehensive Sickle Cell Program at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

San Diego – State-of-the-art guidelines for treating sickle cell disease are actively being developed and could be released as early as the spring of 2019, according to Robert Liem, MD, chair of the American Society of Hematology coordination panel for the initiative.

The new clinical practice recommendations will expand on 2014 guidelines published by the National Heart, Lung, and Blood Institute in a way that will help both hematologists and nonhematologists who take care of patients with sickle cell disease, Dr. Liem said in a video interview at the annual meeting of the American Society of Hematology.

Five different guidelines are under development to cover different aspects of acute and chronic complications of sickle cell disease, including pain, cardiopulmonary and kidney disease, cerebrovascular disease, transfusion support, and stem cell transplantation.

Watch the video to learn more about the guideline effort from the perspective of Dr. Liem, who is also the director of the Comprehensive Sickle Cell Program at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

Researchers have found a significant independent association between nocturnal hypoxemia and risk of incident atrial fibrillation (AF) in patients with obstructive sleep apnea (OSA), which they believe may help prevent the development of AF in this population, according to recent research published in the journal CHEST^®.

“These findings are consistent with those of previous studies suggesting that these groups, who are typically at somewhat lower risk of [atrial fibrillation], might be especially vulnerable to the effects of [obstructive sleep apnea] and hypoxemia,” Tetyana Kendzerska, MD, PhD, of the University of Ottawa in Ottawa, and her colleagues wrote in their study.

They performed an analysis of 8,256 patients with data linked to a provincial health administrative database who had suspected OSA who underwent a sleep study at a large academic hospital between 1994 and 2010. The patients were median 47 years old; 62% of the cohort were men, 28% had an apnea-hypopnea index (AHI) of greater than 30 events per hour, and 6% spent more than 30% of the time during sleep with less than 90% oxygen saturation.

Overall, 173 of 8,256 patients (2.1%) developed AF during the study period. In patients with suspected OSA and who were arrhythmia free, nocturnal hypoxemia significantly increased the risk of incident hospitalized AF (hazard ratio, 2.47; 95% confidence interval, 1.64-3.71) over median 10 years of follow-up (interquartile range, 7-13 years) after the researchers controlled for age, sex, chronic obstructive pulmonary disease, history of heart failure, smoking status, nocturnal hypoxemia, and pulmonary embolism, and this association remained significant after adjustment for body mass index and hypertension (HR, 1.77; 95% CI, 1.15-2.74).

“These findings support a relationship between OSA, chronic nocturnal hypoxemia, and the development of [atrial fibrillation], and may be used to identify those patients with OSA who are at greatest risk of developing AF.”

Researchers cited the observational design, retrospective data collection, and examining hospitalized AF only as limitations in the study. However, they noted that clinical data was collected prospectively and the inability to adjust to positive airway pressure would push results to the null with regard to unstudied confounders.

The authors reported no relevant conflicts of interest.

SOURCE: Kendzerska T et al. CHEST. 2018;doi:10.1016/j.chest.2018.08.1075.

Researchers have found a significant independent association between nocturnal hypoxemia and risk of incident atrial fibrillation (AF) in patients with obstructive sleep apnea (OSA), which they believe may help prevent the development of AF in this population, according to recent research published in the journal CHEST^®.

“These findings are consistent with those of previous studies suggesting that these groups, who are typically at somewhat lower risk of [atrial fibrillation], might be especially vulnerable to the effects of [obstructive sleep apnea] and hypoxemia,” Tetyana Kendzerska, MD, PhD, of the University of Ottawa in Ottawa, and her colleagues wrote in their study.

They performed an analysis of 8,256 patients with data linked to a provincial health administrative database who had suspected OSA who underwent a sleep study at a large academic hospital between 1994 and 2010. The patients were median 47 years old; 62% of the cohort were men, 28% had an apnea-hypopnea index (AHI) of greater than 30 events per hour, and 6% spent more than 30% of the time during sleep with less than 90% oxygen saturation.

Overall, 173 of 8,256 patients (2.1%) developed AF during the study period. In patients with suspected OSA and who were arrhythmia free, nocturnal hypoxemia significantly increased the risk of incident hospitalized AF (hazard ratio, 2.47; 95% confidence interval, 1.64-3.71) over median 10 years of follow-up (interquartile range, 7-13 years) after the researchers controlled for age, sex, chronic obstructive pulmonary disease, history of heart failure, smoking status, nocturnal hypoxemia, and pulmonary embolism, and this association remained significant after adjustment for body mass index and hypertension (HR, 1.77; 95% CI, 1.15-2.74).

“These findings support a relationship between OSA, chronic nocturnal hypoxemia, and the development of [atrial fibrillation], and may be used to identify those patients with OSA who are at greatest risk of developing AF.”

Researchers cited the observational design, retrospective data collection, and examining hospitalized AF only as limitations in the study. However, they noted that clinical data was collected prospectively and the inability to adjust to positive airway pressure would push results to the null with regard to unstudied confounders.

The authors reported no relevant conflicts of interest.

SOURCE: Kendzerska T et al. CHEST. 2018;doi:10.1016/j.chest.2018.08.1075.

Researchers have found a significant independent association between nocturnal hypoxemia and risk of incident atrial fibrillation (AF) in patients with obstructive sleep apnea (OSA), which they believe may help prevent the development of AF in this population, according to recent research published in the journal CHEST^®.

“These findings are consistent with those of previous studies suggesting that these groups, who are typically at somewhat lower risk of [atrial fibrillation], might be especially vulnerable to the effects of [obstructive sleep apnea] and hypoxemia,” Tetyana Kendzerska, MD, PhD, of the University of Ottawa in Ottawa, and her colleagues wrote in their study.

They performed an analysis of 8,256 patients with data linked to a provincial health administrative database who had suspected OSA who underwent a sleep study at a large academic hospital between 1994 and 2010. The patients were median 47 years old; 62% of the cohort were men, 28% had an apnea-hypopnea index (AHI) of greater than 30 events per hour, and 6% spent more than 30% of the time during sleep with less than 90% oxygen saturation.

Overall, 173 of 8,256 patients (2.1%) developed AF during the study period. In patients with suspected OSA and who were arrhythmia free, nocturnal hypoxemia significantly increased the risk of incident hospitalized AF (hazard ratio, 2.47; 95% confidence interval, 1.64-3.71) over median 10 years of follow-up (interquartile range, 7-13 years) after the researchers controlled for age, sex, chronic obstructive pulmonary disease, history of heart failure, smoking status, nocturnal hypoxemia, and pulmonary embolism, and this association remained significant after adjustment for body mass index and hypertension (HR, 1.77; 95% CI, 1.15-2.74).

“These findings support a relationship between OSA, chronic nocturnal hypoxemia, and the development of [atrial fibrillation], and may be used to identify those patients with OSA who are at greatest risk of developing AF.”

Researchers cited the observational design, retrospective data collection, and examining hospitalized AF only as limitations in the study. However, they noted that clinical data was collected prospectively and the inability to adjust to positive airway pressure would push results to the null with regard to unstudied confounders.

The authors reported no relevant conflicts of interest.

SOURCE: Kendzerska T et al. CHEST. 2018;doi:10.1016/j.chest.2018.08.1075.

SAN DIEGO – Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in patients with primary hemophagocytic lymphohistiocytosis (HLH), according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.

Andrew D. Bowser/MDedge News

The recently approved agent should be considered a new therapeutic option for this rare and life-threatening syndrome because of its targeted mode of action, Dr. Locatelli and his coinvestigators reported at the annual meeting of the American Society of Hematology.

Multiple lines of evidence have pointed to interferon gamma as a “rational target” in this disease, and elevated levels of interferon gamma are consistently observed in patients with HLH, Dr. Locatelli said in a press conference at the meeting.

Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.

Primary HLH is a rare, life-threatening syndrome of hyperinflammation, characterized by prolonged fever, cytopenias, and splenomegaly and hepatomegaly, among other clinical manifestations, Dr. Locatelli said.

In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.

The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks, or extended to the point of allogeneic hematopoietic stem cell transplantation (HSCT), if needed.

The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported. The overall response rate was 64.7% for all 34 treated patients (95% confidence interval, 46% to 80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P = .0134), reported data show.

Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.

Common adverse events in the study included infections, infusion-related reactions, pyrexia, and hypertension, while one patient had disseminated histoplasmosis that resolved with appropriate treatment, according to investigators.

In light of these results, the Food and Drug Administration approved emapalumab on Nov. 20, 2018, for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease, or intolerance to conventional HLH treatments.

There is “certainly room for enlarging the indication” to first-line treatment of HLH once a sufficient number of previously untreated patients have been treated with the monoclonal antibody, Dr. Locatelli said.

However, a randomized trial would not be feasible, he said. “It’s a very rare disease, and it would be almost impossible to run a prospective, randomized trial in a reasonable period of time.”

The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.

SOURCE: Locatelli F et al. ASH 2018; Abstract LBA-6.

SAN DIEGO – Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in patients with primary hemophagocytic lymphohistiocytosis (HLH), according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.

Andrew D. Bowser/MDedge News

The recently approved agent should be considered a new therapeutic option for this rare and life-threatening syndrome because of its targeted mode of action, Dr. Locatelli and his coinvestigators reported at the annual meeting of the American Society of Hematology.

Multiple lines of evidence have pointed to interferon gamma as a “rational target” in this disease, and elevated levels of interferon gamma are consistently observed in patients with HLH, Dr. Locatelli said in a press conference at the meeting.

Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.

Primary HLH is a rare, life-threatening syndrome of hyperinflammation, characterized by prolonged fever, cytopenias, and splenomegaly and hepatomegaly, among other clinical manifestations, Dr. Locatelli said.

In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.

The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks, or extended to the point of allogeneic hematopoietic stem cell transplantation (HSCT), if needed.

The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported. The overall response rate was 64.7% for all 34 treated patients (95% confidence interval, 46% to 80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P = .0134), reported data show.

Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.

Common adverse events in the study included infections, infusion-related reactions, pyrexia, and hypertension, while one patient had disseminated histoplasmosis that resolved with appropriate treatment, according to investigators.

In light of these results, the Food and Drug Administration approved emapalumab on Nov. 20, 2018, for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease, or intolerance to conventional HLH treatments.

There is “certainly room for enlarging the indication” to first-line treatment of HLH once a sufficient number of previously untreated patients have been treated with the monoclonal antibody, Dr. Locatelli said.

However, a randomized trial would not be feasible, he said. “It’s a very rare disease, and it would be almost impossible to run a prospective, randomized trial in a reasonable period of time.”

The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.

SOURCE: Locatelli F et al. ASH 2018; Abstract LBA-6.

SAN DIEGO – Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in patients with primary hemophagocytic lymphohistiocytosis (HLH), according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.

Andrew D. Bowser/MDedge News

The recently approved agent should be considered a new therapeutic option for this rare and life-threatening syndrome because of its targeted mode of action, Dr. Locatelli and his coinvestigators reported at the annual meeting of the American Society of Hematology.

Multiple lines of evidence have pointed to interferon gamma as a “rational target” in this disease, and elevated levels of interferon gamma are consistently observed in patients with HLH, Dr. Locatelli said in a press conference at the meeting.

Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.

Primary HLH is a rare, life-threatening syndrome of hyperinflammation, characterized by prolonged fever, cytopenias, and splenomegaly and hepatomegaly, among other clinical manifestations, Dr. Locatelli said.

In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.

The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks, or extended to the point of allogeneic hematopoietic stem cell transplantation (HSCT), if needed.

The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported. The overall response rate was 64.7% for all 34 treated patients (95% confidence interval, 46% to 80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P = .0134), reported data show.

Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.

Common adverse events in the study included infections, infusion-related reactions, pyrexia, and hypertension, while one patient had disseminated histoplasmosis that resolved with appropriate treatment, according to investigators.

In light of these results, the Food and Drug Administration approved emapalumab on Nov. 20, 2018, for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease, or intolerance to conventional HLH treatments.

There is “certainly room for enlarging the indication” to first-line treatment of HLH once a sufficient number of previously untreated patients have been treated with the monoclonal antibody, Dr. Locatelli said.

However, a randomized trial would not be feasible, he said. “It’s a very rare disease, and it would be almost impossible to run a prospective, randomized trial in a reasonable period of time.”

The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.

SOURCE: Locatelli F et al. ASH 2018; Abstract LBA-6.