The ratio of apolipoproteins B and A1 (apo B/A1) is an independent prognostic factor in patients with metastatic renal cell carcinoma, according to authors of a recent retrospective study.

The apo B/A1 ratio, evaluated prior to cytoreductive nephrectomy, was significantly linked with poor progression-free survival and overall survival, according to Fan Zhang, MD, of the Chinese PLA General Hospital in Beijing and coauthors.

Those findings suggest that patients with metastatic RCC should receive “consistent follow-up” that includes evaluation of that ratio, Dr. Zhang and colleagues said.

“As a novel prognostic factor, the preoperative apo B/A1 ratio can be utilized as a supplement to improve the current prognostic evaluation and treatment decision for patients with metastatic RCC,” they wrote in Urologic Oncology.

Apo B and A1, which are predominant components of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), respectively, have “extensive connections” with cardiovascular disease, diabetes, and Alzheimer disease, the authors said.

The apo B/A1 ratio is a known risk index for cardiovascular disease, and in recent studies, it appeared to have some value in prognosis and prediction of gastric and colorectal cancer, among other neoplasms, they added.

In their retrospective study, Dr. Zhang and colleagues analyzed data on 287 metastatic RCC patients who underwent cytoreductive nephrectomy at the Chinese PLA General Hospital. The median age of the patients was 56 years, and the median apo B/A1 ratio was 0.859.

Significantly poorer progression-free survival was seen in the group of patients with a preoperative apo B/A1 ratio over the cutoff of 0.977 (P less than .0001) compared with those under the cutoff, the investigators reported. Likewise, overall survival was poorer for patients with an apo B/A1 ratio over a cutoff of 0.847 (P = .0005).

The apo B/A1 ratio was higher in patients with Fuhrman grade 3-4 versus grade 1-2 patients (P = .010), though the investigators said no significant differences in the ratio were seen in patients stratified by age, body mass index, fatty liver, number of metastases, among other subgroup analyses.

Multivariate analysis revealed that the two independent prognostic factors for progression-free survival were preoperative apo B/A1 ratio and Fuhrman grade, with hazard ratios of 3.131 and 1.906, respectively (P less than .001 for both), while independent prognostic factors for overall survival also included the apo B/A1 ratio (hazard ratio, 2.173; P less than .001) and Fuhrman grade, along with tumor necrosis and receiving targeted therapy.

This retrospective study was limited by relatively small samples from a single center, and the prognostic value of the apo B/A1 ratio needs to be verified in other studies, investigators said.

“Peripheral blood biomarkers only provide a supplement to the traditional prognostic factors in the prediction of the prognosis for patients with metastatic RCC, and are still unable to replace it,” Dr. Zhang and associates said.

The Beijing Natural Science Foundation supported the study. Dr. Zhang and coauthors had no disclosed conflicts of interest related to the work.

SOURCE: Zhang F et al. Urol Oncol. 2018 Nov 30. doi: 10.1016/j.urolonc.2018.11.010.

The ratio of apolipoproteins B and A1 (apo B/A1) is an independent prognostic factor in patients with metastatic renal cell carcinoma, according to authors of a recent retrospective study.

The apo B/A1 ratio, evaluated prior to cytoreductive nephrectomy, was significantly linked with poor progression-free survival and overall survival, according to Fan Zhang, MD, of the Chinese PLA General Hospital in Beijing and coauthors.

Those findings suggest that patients with metastatic RCC should receive “consistent follow-up” that includes evaluation of that ratio, Dr. Zhang and colleagues said.

“As a novel prognostic factor, the preoperative apo B/A1 ratio can be utilized as a supplement to improve the current prognostic evaluation and treatment decision for patients with metastatic RCC,” they wrote in Urologic Oncology.

Apo B and A1, which are predominant components of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), respectively, have “extensive connections” with cardiovascular disease, diabetes, and Alzheimer disease, the authors said.

The apo B/A1 ratio is a known risk index for cardiovascular disease, and in recent studies, it appeared to have some value in prognosis and prediction of gastric and colorectal cancer, among other neoplasms, they added.

In their retrospective study, Dr. Zhang and colleagues analyzed data on 287 metastatic RCC patients who underwent cytoreductive nephrectomy at the Chinese PLA General Hospital. The median age of the patients was 56 years, and the median apo B/A1 ratio was 0.859.

Significantly poorer progression-free survival was seen in the group of patients with a preoperative apo B/A1 ratio over the cutoff of 0.977 (P less than .0001) compared with those under the cutoff, the investigators reported. Likewise, overall survival was poorer for patients with an apo B/A1 ratio over a cutoff of 0.847 (P = .0005).

The apo B/A1 ratio was higher in patients with Fuhrman grade 3-4 versus grade 1-2 patients (P = .010), though the investigators said no significant differences in the ratio were seen in patients stratified by age, body mass index, fatty liver, number of metastases, among other subgroup analyses.

Multivariate analysis revealed that the two independent prognostic factors for progression-free survival were preoperative apo B/A1 ratio and Fuhrman grade, with hazard ratios of 3.131 and 1.906, respectively (P less than .001 for both), while independent prognostic factors for overall survival also included the apo B/A1 ratio (hazard ratio, 2.173; P less than .001) and Fuhrman grade, along with tumor necrosis and receiving targeted therapy.

This retrospective study was limited by relatively small samples from a single center, and the prognostic value of the apo B/A1 ratio needs to be verified in other studies, investigators said.

“Peripheral blood biomarkers only provide a supplement to the traditional prognostic factors in the prediction of the prognosis for patients with metastatic RCC, and are still unable to replace it,” Dr. Zhang and associates said.

The Beijing Natural Science Foundation supported the study. Dr. Zhang and coauthors had no disclosed conflicts of interest related to the work.

SOURCE: Zhang F et al. Urol Oncol. 2018 Nov 30. doi: 10.1016/j.urolonc.2018.11.010.

The ratio of apolipoproteins B and A1 (apo B/A1) is an independent prognostic factor in patients with metastatic renal cell carcinoma, according to authors of a recent retrospective study.

The apo B/A1 ratio, evaluated prior to cytoreductive nephrectomy, was significantly linked with poor progression-free survival and overall survival, according to Fan Zhang, MD, of the Chinese PLA General Hospital in Beijing and coauthors.

Those findings suggest that patients with metastatic RCC should receive “consistent follow-up” that includes evaluation of that ratio, Dr. Zhang and colleagues said.

“As a novel prognostic factor, the preoperative apo B/A1 ratio can be utilized as a supplement to improve the current prognostic evaluation and treatment decision for patients with metastatic RCC,” they wrote in Urologic Oncology.

Apo B and A1, which are predominant components of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), respectively, have “extensive connections” with cardiovascular disease, diabetes, and Alzheimer disease, the authors said.

The apo B/A1 ratio is a known risk index for cardiovascular disease, and in recent studies, it appeared to have some value in prognosis and prediction of gastric and colorectal cancer, among other neoplasms, they added.

In their retrospective study, Dr. Zhang and colleagues analyzed data on 287 metastatic RCC patients who underwent cytoreductive nephrectomy at the Chinese PLA General Hospital. The median age of the patients was 56 years, and the median apo B/A1 ratio was 0.859.

Significantly poorer progression-free survival was seen in the group of patients with a preoperative apo B/A1 ratio over the cutoff of 0.977 (P less than .0001) compared with those under the cutoff, the investigators reported. Likewise, overall survival was poorer for patients with an apo B/A1 ratio over a cutoff of 0.847 (P = .0005).

The apo B/A1 ratio was higher in patients with Fuhrman grade 3-4 versus grade 1-2 patients (P = .010), though the investigators said no significant differences in the ratio were seen in patients stratified by age, body mass index, fatty liver, number of metastases, among other subgroup analyses.

Multivariate analysis revealed that the two independent prognostic factors for progression-free survival were preoperative apo B/A1 ratio and Fuhrman grade, with hazard ratios of 3.131 and 1.906, respectively (P less than .001 for both), while independent prognostic factors for overall survival also included the apo B/A1 ratio (hazard ratio, 2.173; P less than .001) and Fuhrman grade, along with tumor necrosis and receiving targeted therapy.

This retrospective study was limited by relatively small samples from a single center, and the prognostic value of the apo B/A1 ratio needs to be verified in other studies, investigators said.

“Peripheral blood biomarkers only provide a supplement to the traditional prognostic factors in the prediction of the prognosis for patients with metastatic RCC, and are still unable to replace it,” Dr. Zhang and associates said.

The Beijing Natural Science Foundation supported the study. Dr. Zhang and coauthors had no disclosed conflicts of interest related to the work.

SOURCE: Zhang F et al. Urol Oncol. 2018 Nov 30. doi: 10.1016/j.urolonc.2018.11.010.

IgA vasculitis, also called Henoch-Schönlein purpura, increases risks for hypertension and chronic kidney disease (CKD), according to a retrospective study of more than 13,000 patients with IgAV.

In patients with adult-onset IgA vasculitis (IgAV), mortality risk is also increased, reported first author Alexander Tracy and his colleagues at the University of Birmingham (England).

“Long-term health outcomes of adult-onset IgAV are not well characterized,” the investigators wrote in Annals of Rheumatic Disease. “Most evidence regarding complications of IgAV in adults derives from case reports and case series; there is need for controlled epidemiological studies to address this question.”

The retrospective study compared 2,828 patients with adult-onset IgAV and 10,405 patients with childhood-onset IgAV against sex- and age-matched controls. Patients diagnosed at age 16 years or older were classified as having adult-onset disease. The investigators drew their data from The Health Improvement Network database, which includes 3.6 million active patients from more than 675 general practices in the United Kingdom. Patients in the present study were diagnosed with IgAV between 2005 and 2016. After diagnosis, participant follow-up continued until any of the following occurred: outcome event, patient left practice, death, the practice stopped contributing data, or the study ended. Primary outcomes for adult-onset patients were venous thromboembolism (VTE), ischemic heart disease, hypertension, stage 3-5 CKD, stroke/transient ischemic attack, and all-cause mortality. Primary outcomes for patients with childhood-onset disease were limited to CKD, hypertension, and VTE.

The incidence of childhood-onset IgAV was 27.22 per 100,000 person-years, whereas adult-onset disease was much less common at 2.20 per 100,000 person-years. Mean age at onset of childhood IgAV was 6.68 years. The adult-onset group had a mean age at diagnosis of 38.1 years.


Compared with controls, all patients with IgAV, regardless of onset age, had increased risks of hypertension (adult-onset adjusted hazard ratio, 1.42; P less than .001; childhood-onset aHR, 1.52; P less than .001) and CKD (adult-onset aHR, 1.54; P less than .001; childhood-onset aHR, 1.89; P = .01). Patients with adult-onset IgAV showed increased risk of death, compared with controls (aHR, 1.27; P = .006). No associations were found between IgAV and stroke/transient ischemic attack, VTE, or ischemic heart disease.

“These findings emphasize the importance of blood pressure and renal function monitoring in patients with IgAV,” the investigators concluded. “Our data also suggest that IgAV should not be considered a ‘single-hit’ disease, but that clinicians should monitor for long-term sequelae. Further research is required to clarify the cause of hypertension in patients with IgAV, and to investigate whether such patients suffer from additional long-term sequelae than that are currently unrecognized.”

The investigators reported no funding sources or conflicts or interest.

SOURCE: Tracy A et al. Ann Rheum Dis. 2018 Nov 28. doi: 10.1136/annrheumdis-2018-214142.

IgA vasculitis, also called Henoch-Schönlein purpura, increases risks for hypertension and chronic kidney disease (CKD), according to a retrospective study of more than 13,000 patients with IgAV.

In patients with adult-onset IgA vasculitis (IgAV), mortality risk is also increased, reported first author Alexander Tracy and his colleagues at the University of Birmingham (England).

“Long-term health outcomes of adult-onset IgAV are not well characterized,” the investigators wrote in Annals of Rheumatic Disease. “Most evidence regarding complications of IgAV in adults derives from case reports and case series; there is need for controlled epidemiological studies to address this question.”

The retrospective study compared 2,828 patients with adult-onset IgAV and 10,405 patients with childhood-onset IgAV against sex- and age-matched controls. Patients diagnosed at age 16 years or older were classified as having adult-onset disease. The investigators drew their data from The Health Improvement Network database, which includes 3.6 million active patients from more than 675 general practices in the United Kingdom. Patients in the present study were diagnosed with IgAV between 2005 and 2016. After diagnosis, participant follow-up continued until any of the following occurred: outcome event, patient left practice, death, the practice stopped contributing data, or the study ended. Primary outcomes for adult-onset patients were venous thromboembolism (VTE), ischemic heart disease, hypertension, stage 3-5 CKD, stroke/transient ischemic attack, and all-cause mortality. Primary outcomes for patients with childhood-onset disease were limited to CKD, hypertension, and VTE.

The incidence of childhood-onset IgAV was 27.22 per 100,000 person-years, whereas adult-onset disease was much less common at 2.20 per 100,000 person-years. Mean age at onset of childhood IgAV was 6.68 years. The adult-onset group had a mean age at diagnosis of 38.1 years.


Compared with controls, all patients with IgAV, regardless of onset age, had increased risks of hypertension (adult-onset adjusted hazard ratio, 1.42; P less than .001; childhood-onset aHR, 1.52; P less than .001) and CKD (adult-onset aHR, 1.54; P less than .001; childhood-onset aHR, 1.89; P = .01). Patients with adult-onset IgAV showed increased risk of death, compared with controls (aHR, 1.27; P = .006). No associations were found between IgAV and stroke/transient ischemic attack, VTE, or ischemic heart disease.

“These findings emphasize the importance of blood pressure and renal function monitoring in patients with IgAV,” the investigators concluded. “Our data also suggest that IgAV should not be considered a ‘single-hit’ disease, but that clinicians should monitor for long-term sequelae. Further research is required to clarify the cause of hypertension in patients with IgAV, and to investigate whether such patients suffer from additional long-term sequelae than that are currently unrecognized.”

The investigators reported no funding sources or conflicts or interest.

SOURCE: Tracy A et al. Ann Rheum Dis. 2018 Nov 28. doi: 10.1136/annrheumdis-2018-214142.

IgA vasculitis, also called Henoch-Schönlein purpura, increases risks for hypertension and chronic kidney disease (CKD), according to a retrospective study of more than 13,000 patients with IgAV.

In patients with adult-onset IgA vasculitis (IgAV), mortality risk is also increased, reported first author Alexander Tracy and his colleagues at the University of Birmingham (England).

“Long-term health outcomes of adult-onset IgAV are not well characterized,” the investigators wrote in Annals of Rheumatic Disease. “Most evidence regarding complications of IgAV in adults derives from case reports and case series; there is need for controlled epidemiological studies to address this question.”

The retrospective study compared 2,828 patients with adult-onset IgAV and 10,405 patients with childhood-onset IgAV against sex- and age-matched controls. Patients diagnosed at age 16 years or older were classified as having adult-onset disease. The investigators drew their data from The Health Improvement Network database, which includes 3.6 million active patients from more than 675 general practices in the United Kingdom. Patients in the present study were diagnosed with IgAV between 2005 and 2016. After diagnosis, participant follow-up continued until any of the following occurred: outcome event, patient left practice, death, the practice stopped contributing data, or the study ended. Primary outcomes for adult-onset patients were venous thromboembolism (VTE), ischemic heart disease, hypertension, stage 3-5 CKD, stroke/transient ischemic attack, and all-cause mortality. Primary outcomes for patients with childhood-onset disease were limited to CKD, hypertension, and VTE.

The incidence of childhood-onset IgAV was 27.22 per 100,000 person-years, whereas adult-onset disease was much less common at 2.20 per 100,000 person-years. Mean age at onset of childhood IgAV was 6.68 years. The adult-onset group had a mean age at diagnosis of 38.1 years.


Compared with controls, all patients with IgAV, regardless of onset age, had increased risks of hypertension (adult-onset adjusted hazard ratio, 1.42; P less than .001; childhood-onset aHR, 1.52; P less than .001) and CKD (adult-onset aHR, 1.54; P less than .001; childhood-onset aHR, 1.89; P = .01). Patients with adult-onset IgAV showed increased risk of death, compared with controls (aHR, 1.27; P = .006). No associations were found between IgAV and stroke/transient ischemic attack, VTE, or ischemic heart disease.

“These findings emphasize the importance of blood pressure and renal function monitoring in patients with IgAV,” the investigators concluded. “Our data also suggest that IgAV should not be considered a ‘single-hit’ disease, but that clinicians should monitor for long-term sequelae. Further research is required to clarify the cause of hypertension in patients with IgAV, and to investigate whether such patients suffer from additional long-term sequelae than that are currently unrecognized.”

The investigators reported no funding sources or conflicts or interest.

SOURCE: Tracy A et al. Ann Rheum Dis. 2018 Nov 28. doi: 10.1136/annrheumdis-2018-214142.

As clinicians trained in the care of children, we have struggled in recent years with how much care is appropriate to provide to the parents of our young charges.

Ridofranz/Thinkstock

Gradual progression has occurred from recognizing postpartum depression as affecting infants, to recommending screening, to creation of a billing code for screening as “for the benefit of” the child, and increasingly even being paid for that code. We now see referral of depressed parents as within our scope of practice with the goal of protecting the child’s emotional development from the caregiver’s altered mental condition, as well as relieving the parent’s suffering. Some of us even provide treatment ourselves.

While the family history has been our standard way of assessing “transgenerational transmission” of risk for physical and mental health conditions, parenting practices are a more direct transmission threat, and one more amenable to our intervention.

Aversive parenting acts happen to many people growing up, but how the parent thinks about these seems to make the difference between consciously protecting the child from similar experiences or unconsciously playing them out in the child’s life. With 64% of U.S. adults reporting at least one adverse childhood experience (ACE), many of which were acts or omissions by their parents, we need to be vigilant to track their translation of past events, “the ghosts,” into present parenting.
 

Just ask

“I barely have time to talk about the child,” you may be saying, “how can I have time to dig into the parent’s issues, much less know what to do?” Exploring for connections to the parent’s past in primary care is most crucial when the parent-child relationship is strained, or the parent’s handling of typical or problematic child behaviors is abnormal, clinically symptomatic, or dangerous. Nonetheless, helping all parents make these connections enriches life and meaning for families, and dramatically strengthens the doctor-family relationship. Then all of our care is more effective.

In my experience, this valuable connection is not difficult to make – it lives just below the surface for most parents. We may want to ask permission first, noting that “our ideas about how to parent tend to be shaped by how we were parented.” By simply asking, “May I ask how your parents would have handled this [behavior or situation]?” we may hear a description of a reasonable approach (sent to my room), denial that this ever came up (I was never as hardheaded as this kid!), blanking out (Things were tough. I have tried to block it all out), or clues to a pattern better not repeated (Oh, my father would have beat me ...). This question also may be useful in elucidating cultural or generational differences between what was done to them and their own intentions that can be hard to bridge. All of these are opportunities for promoting positive parenting by creating empathy for that child of the past to carry forward to the own child in the present.

While we may be lucky to have even one parent at the visit, we should ask the one present the equivalent question of the partner’s past. Even if one parent had a model that he or she wanted to emulate or a ghost to bust, the other may not agree. Conflict between partners undermines management and can create harmful tension. If the parent does not know, this is an important homework assignment to being collaborative coparents.
 

Empathize

After hearing about the past experiences, we should empathize with the parent regarding pain experienced as a child in the past (“That would be very scary for any child”) and ask “How much is this a burden for you now?” to see if help is needed. But this is a key educational moment for us as child development experts to suggest how children of the age they were then might process the events. For example, one might explain reaction to abandonment by a father by saying, “Any 6-year-old whose father left would feel sad and mad, but also might think he had done something wrong or wasn’t worth staying around for.” One might react to a story of abusive discipline by saying, “Children need to feel safe and protected at home. Not knowing when your parent is going to hurt you could produce lifelong anxiety and trouble trusting your closest relationships.” Watch to see if this connects for them.

Selma Fraiberg, in the classic article “Ghosts in the Nursery,”¹ noted that if parents have come to empathize with their past hurting selves, they will work to prevent similar pain for their own children. If they have dealt with these experiences by identifying with the aggressive or neglectful adult or blanking the memory, they are more likely to act out similar practices with their children.

For some, being able to tolerate reviewing these painful times enough to experience empathy for the child may require years of work with a trusted therapist. We should be prepared to refer if the parents are in distress. But for many, getting our help to understand how a child might feel and later act after these experiences may be enough to interrupt the transmission. We can try to elicit current impact of the past (“How are those experiences affecting your parenting now?”). This question, expecting impact, often causes parents to stop short and think. While at first denying impact, if I have been compassionate and nonjudgmental in asking, they often return with more insight.
 

Help with parenting issues

After eliciting perceptions of the past, I find it useful to ask, “So, what have (the two of) you decided” about how to manage [the problematic parenting situation]?” The implication is that parenting actions are decisions. Making this decision process overt may reveal that they are having blank out moments of impulsive action, or ambivalence with thoughts and feelings in conflict, or arguments resulting in standoffs. A common reaction to hurts in the past is for parents to strongly avoid doing as their own parents did, but then have no plan at all, get increasingly emotional, and finally blow up and scream or hit or storm off ineffectually. We can help them pick out one or two stressful situations, often perceived disrespect or defiance by the child, and plan steps for when it comes up again – as hot-button issues always do. It is important to let them know that their “emotion brain” is likely to speak up first under stress and the “thinking brain” takes longer. We, and they, need to be patient and congratulate them for little bits of progress in having rationality win.

Don’t forget that children adapt to the parenting they receive and develop reactions that may interfere with seeing their parents in a new mode of trust and kindness. A child may have defended him/herself from the emotional pain of not feeling safe or protected by the parent who is acting out a ghost and may react by laughing, running, spitting, hitting, shutting down, pushing the parent away, or saying “I don’t care.” The child’s reaction, too, takes time and consistent responsiveness to change to accept new parenting patterns. It can be painful to the newly-aware parents to recognize these behaviors are caused, at least in part, by their own actions, especially when it is a repetition of their own childhood experiences. We can be the patient, empathic coach – believing in their good intentions as they develop as parents – just as they would have wanted from their parents when they were growing up.



Dr. Howard is assistant professor of pediatrics at The Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert for MDedge News. E-mail her at [email protected].


Reference

1. “Ghosts in the Nursery: A Psychoanalytic Approach to the Problems of Impaired Infant-Mother Relationships,” J Am Acad Child Psychiatry. 1975 Summer;14(3);387-421.

As clinicians trained in the care of children, we have struggled in recent years with how much care is appropriate to provide to the parents of our young charges.

Ridofranz/Thinkstock

Gradual progression has occurred from recognizing postpartum depression as affecting infants, to recommending screening, to creation of a billing code for screening as “for the benefit of” the child, and increasingly even being paid for that code. We now see referral of depressed parents as within our scope of practice with the goal of protecting the child’s emotional development from the caregiver’s altered mental condition, as well as relieving the parent’s suffering. Some of us even provide treatment ourselves.

While the family history has been our standard way of assessing “transgenerational transmission” of risk for physical and mental health conditions, parenting practices are a more direct transmission threat, and one more amenable to our intervention.

Aversive parenting acts happen to many people growing up, but how the parent thinks about these seems to make the difference between consciously protecting the child from similar experiences or unconsciously playing them out in the child’s life. With 64% of U.S. adults reporting at least one adverse childhood experience (ACE), many of which were acts or omissions by their parents, we need to be vigilant to track their translation of past events, “the ghosts,” into present parenting.
 

Just ask

“I barely have time to talk about the child,” you may be saying, “how can I have time to dig into the parent’s issues, much less know what to do?” Exploring for connections to the parent’s past in primary care is most crucial when the parent-child relationship is strained, or the parent’s handling of typical or problematic child behaviors is abnormal, clinically symptomatic, or dangerous. Nonetheless, helping all parents make these connections enriches life and meaning for families, and dramatically strengthens the doctor-family relationship. Then all of our care is more effective.

In my experience, this valuable connection is not difficult to make – it lives just below the surface for most parents. We may want to ask permission first, noting that “our ideas about how to parent tend to be shaped by how we were parented.” By simply asking, “May I ask how your parents would have handled this [behavior or situation]?” we may hear a description of a reasonable approach (sent to my room), denial that this ever came up (I was never as hardheaded as this kid!), blanking out (Things were tough. I have tried to block it all out), or clues to a pattern better not repeated (Oh, my father would have beat me ...). This question also may be useful in elucidating cultural or generational differences between what was done to them and their own intentions that can be hard to bridge. All of these are opportunities for promoting positive parenting by creating empathy for that child of the past to carry forward to the own child in the present.

While we may be lucky to have even one parent at the visit, we should ask the one present the equivalent question of the partner’s past. Even if one parent had a model that he or she wanted to emulate or a ghost to bust, the other may not agree. Conflict between partners undermines management and can create harmful tension. If the parent does not know, this is an important homework assignment to being collaborative coparents.
 

Empathize

After hearing about the past experiences, we should empathize with the parent regarding pain experienced as a child in the past (“That would be very scary for any child”) and ask “How much is this a burden for you now?” to see if help is needed. But this is a key educational moment for us as child development experts to suggest how children of the age they were then might process the events. For example, one might explain reaction to abandonment by a father by saying, “Any 6-year-old whose father left would feel sad and mad, but also might think he had done something wrong or wasn’t worth staying around for.” One might react to a story of abusive discipline by saying, “Children need to feel safe and protected at home. Not knowing when your parent is going to hurt you could produce lifelong anxiety and trouble trusting your closest relationships.” Watch to see if this connects for them.

Selma Fraiberg, in the classic article “Ghosts in the Nursery,”¹ noted that if parents have come to empathize with their past hurting selves, they will work to prevent similar pain for their own children. If they have dealt with these experiences by identifying with the aggressive or neglectful adult or blanking the memory, they are more likely to act out similar practices with their children.

For some, being able to tolerate reviewing these painful times enough to experience empathy for the child may require years of work with a trusted therapist. We should be prepared to refer if the parents are in distress. But for many, getting our help to understand how a child might feel and later act after these experiences may be enough to interrupt the transmission. We can try to elicit current impact of the past (“How are those experiences affecting your parenting now?”). This question, expecting impact, often causes parents to stop short and think. While at first denying impact, if I have been compassionate and nonjudgmental in asking, they often return with more insight.
 

Help with parenting issues

After eliciting perceptions of the past, I find it useful to ask, “So, what have (the two of) you decided” about how to manage [the problematic parenting situation]?” The implication is that parenting actions are decisions. Making this decision process overt may reveal that they are having blank out moments of impulsive action, or ambivalence with thoughts and feelings in conflict, or arguments resulting in standoffs. A common reaction to hurts in the past is for parents to strongly avoid doing as their own parents did, but then have no plan at all, get increasingly emotional, and finally blow up and scream or hit or storm off ineffectually. We can help them pick out one or two stressful situations, often perceived disrespect or defiance by the child, and plan steps for when it comes up again – as hot-button issues always do. It is important to let them know that their “emotion brain” is likely to speak up first under stress and the “thinking brain” takes longer. We, and they, need to be patient and congratulate them for little bits of progress in having rationality win.

Don’t forget that children adapt to the parenting they receive and develop reactions that may interfere with seeing their parents in a new mode of trust and kindness. A child may have defended him/herself from the emotional pain of not feeling safe or protected by the parent who is acting out a ghost and may react by laughing, running, spitting, hitting, shutting down, pushing the parent away, or saying “I don’t care.” The child’s reaction, too, takes time and consistent responsiveness to change to accept new parenting patterns. It can be painful to the newly-aware parents to recognize these behaviors are caused, at least in part, by their own actions, especially when it is a repetition of their own childhood experiences. We can be the patient, empathic coach – believing in their good intentions as they develop as parents – just as they would have wanted from their parents when they were growing up.



Dr. Howard is assistant professor of pediatrics at The Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert for MDedge News. E-mail her at [email protected].


Reference

1. “Ghosts in the Nursery: A Psychoanalytic Approach to the Problems of Impaired Infant-Mother Relationships,” J Am Acad Child Psychiatry. 1975 Summer;14(3);387-421.

As clinicians trained in the care of children, we have struggled in recent years with how much care is appropriate to provide to the parents of our young charges.

Ridofranz/Thinkstock

Gradual progression has occurred from recognizing postpartum depression as affecting infants, to recommending screening, to creation of a billing code for screening as “for the benefit of” the child, and increasingly even being paid for that code. We now see referral of depressed parents as within our scope of practice with the goal of protecting the child’s emotional development from the caregiver’s altered mental condition, as well as relieving the parent’s suffering. Some of us even provide treatment ourselves.

While the family history has been our standard way of assessing “transgenerational transmission” of risk for physical and mental health conditions, parenting practices are a more direct transmission threat, and one more amenable to our intervention.

Aversive parenting acts happen to many people growing up, but how the parent thinks about these seems to make the difference between consciously protecting the child from similar experiences or unconsciously playing them out in the child’s life. With 64% of U.S. adults reporting at least one adverse childhood experience (ACE), many of which were acts or omissions by their parents, we need to be vigilant to track their translation of past events, “the ghosts,” into present parenting.
 

Just ask

“I barely have time to talk about the child,” you may be saying, “how can I have time to dig into the parent’s issues, much less know what to do?” Exploring for connections to the parent’s past in primary care is most crucial when the parent-child relationship is strained, or the parent’s handling of typical or problematic child behaviors is abnormal, clinically symptomatic, or dangerous. Nonetheless, helping all parents make these connections enriches life and meaning for families, and dramatically strengthens the doctor-family relationship. Then all of our care is more effective.

In my experience, this valuable connection is not difficult to make – it lives just below the surface for most parents. We may want to ask permission first, noting that “our ideas about how to parent tend to be shaped by how we were parented.” By simply asking, “May I ask how your parents would have handled this [behavior or situation]?” we may hear a description of a reasonable approach (sent to my room), denial that this ever came up (I was never as hardheaded as this kid!), blanking out (Things were tough. I have tried to block it all out), or clues to a pattern better not repeated (Oh, my father would have beat me ...). This question also may be useful in elucidating cultural or generational differences between what was done to them and their own intentions that can be hard to bridge. All of these are opportunities for promoting positive parenting by creating empathy for that child of the past to carry forward to the own child in the present.

While we may be lucky to have even one parent at the visit, we should ask the one present the equivalent question of the partner’s past. Even if one parent had a model that he or she wanted to emulate or a ghost to bust, the other may not agree. Conflict between partners undermines management and can create harmful tension. If the parent does not know, this is an important homework assignment to being collaborative coparents.
 

Empathize

After hearing about the past experiences, we should empathize with the parent regarding pain experienced as a child in the past (“That would be very scary for any child”) and ask “How much is this a burden for you now?” to see if help is needed. But this is a key educational moment for us as child development experts to suggest how children of the age they were then might process the events. For example, one might explain reaction to abandonment by a father by saying, “Any 6-year-old whose father left would feel sad and mad, but also might think he had done something wrong or wasn’t worth staying around for.” One might react to a story of abusive discipline by saying, “Children need to feel safe and protected at home. Not knowing when your parent is going to hurt you could produce lifelong anxiety and trouble trusting your closest relationships.” Watch to see if this connects for them.

Selma Fraiberg, in the classic article “Ghosts in the Nursery,”¹ noted that if parents have come to empathize with their past hurting selves, they will work to prevent similar pain for their own children. If they have dealt with these experiences by identifying with the aggressive or neglectful adult or blanking the memory, they are more likely to act out similar practices with their children.

For some, being able to tolerate reviewing these painful times enough to experience empathy for the child may require years of work with a trusted therapist. We should be prepared to refer if the parents are in distress. But for many, getting our help to understand how a child might feel and later act after these experiences may be enough to interrupt the transmission. We can try to elicit current impact of the past (“How are those experiences affecting your parenting now?”). This question, expecting impact, often causes parents to stop short and think. While at first denying impact, if I have been compassionate and nonjudgmental in asking, they often return with more insight.
 

Help with parenting issues

After eliciting perceptions of the past, I find it useful to ask, “So, what have (the two of) you decided” about how to manage [the problematic parenting situation]?” The implication is that parenting actions are decisions. Making this decision process overt may reveal that they are having blank out moments of impulsive action, or ambivalence with thoughts and feelings in conflict, or arguments resulting in standoffs. A common reaction to hurts in the past is for parents to strongly avoid doing as their own parents did, but then have no plan at all, get increasingly emotional, and finally blow up and scream or hit or storm off ineffectually. We can help them pick out one or two stressful situations, often perceived disrespect or defiance by the child, and plan steps for when it comes up again – as hot-button issues always do. It is important to let them know that their “emotion brain” is likely to speak up first under stress and the “thinking brain” takes longer. We, and they, need to be patient and congratulate them for little bits of progress in having rationality win.

Don’t forget that children adapt to the parenting they receive and develop reactions that may interfere with seeing their parents in a new mode of trust and kindness. A child may have defended him/herself from the emotional pain of not feeling safe or protected by the parent who is acting out a ghost and may react by laughing, running, spitting, hitting, shutting down, pushing the parent away, or saying “I don’t care.” The child’s reaction, too, takes time and consistent responsiveness to change to accept new parenting patterns. It can be painful to the newly-aware parents to recognize these behaviors are caused, at least in part, by their own actions, especially when it is a repetition of their own childhood experiences. We can be the patient, empathic coach – believing in their good intentions as they develop as parents – just as they would have wanted from their parents when they were growing up.



Dr. Howard is assistant professor of pediatrics at The Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert for MDedge News. E-mail her at [email protected].


Reference

1. “Ghosts in the Nursery: A Psychoanalytic Approach to the Problems of Impaired Infant-Mother Relationships,” J Am Acad Child Psychiatry. 1975 Summer;14(3);387-421.

SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.

The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.

“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.

The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.

The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.

The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.

Patients were defined as being DTC positive if one or more DTCs were detected.

A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).

At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).

Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).

In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.

“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.

There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).

“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.

Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.

SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.

SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.

The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.

“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.

The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.

The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.

The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.

Patients were defined as being DTC positive if one or more DTCs were detected.

A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).

At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).

Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).

In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.

“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.

There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).

“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.

Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.

SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.

SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.

The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.

“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.

The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.

The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.

The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.

Patients were defined as being DTC positive if one or more DTCs were detected.

A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).

At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).

Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).

In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.

“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.

There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).

“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.

Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.

SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.

SAN DIEGO – The combination of ibrutinib and rituximab was associated with a two-thirds reduction in chronic lymphocytic leukemia (CLL) progression, compared with standard chemoimmunotherapy in patients younger than 70 years old, interim results of a phase 3 randomized trial showed.

Among 529 patients with previously untreated, symptomatic CLL randomly assigned to ibrutinib-rituximab (IR) or to chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR), the IR regimen was associated with a 65% reduction in risk for disease progression, which was the trial’s primary endpoint.

The IR regimen was also associated with better overall survival out to 4 years of follow-up, reported Tait D. Shanafelt, MD, of Stanford (Calif.) University.

“This establishes ibrutinib-based therapy as the most effective treatment tested to date in this disease for untreated patients,” he said at a media briefing prior at the annual meeting of the American Society of Hematology.

The study results are likely to dethrone FCR as the most active chemoimmunotherapy regimen against CLL, Dr. Shanafelt said.

In the ECOG-ACRIN Cancer Research Group E1912 trial, 529 patients aged 70 or younger with previously untreated CLL were enrolled and randomly assigned on a 2:1 basis to either standard therapy with six cycles of FCR according to standard protocols (175 patients), or IR, with ibrutinib 420 mg daily for each cycle, and rituximab delivered 50 mg/m² intravenously on day 1 of cycle 2, and 325 mg/m² on day 2 of the same cycle, and 500 mg/m² on day 1 for all remaining cycles (354 patients).

From cycle 8 until progression, patients in the IR arm received daily ibrutinib 420 mg.

Dr. Shanafelt presented results from both an intention-to-treat analysis and a per-protocol analysis excluding 22 patients in the IR arm and 9 patients in the FCR arm who were randomized but later found not to meet eligibility criteria.

After a mean follow-up of 34 months, there were 37 PFS events in the IR arm, compared with 40 events in the FCR arm in an intention-to-treat analysis. The difference translated into a hazard ratio for progression of 0.35 with IR (P less than .00001).

The results were similar in the per-protocol analysis, with an HR of 0.32 favoring IR (P less than .00001).*

There were four deaths in the IR arm, compared with 10 in the FCR arm at the time of the data lock, translating into a hazard ratio (HR) for overall survival of 0.17 (P less than .0003) in the intention-to-treat analysis, and 0.13 in the per-protocol analysis (P less than .0001).

Dr. Shanafelt noted that although the overall number of deaths was relatively small, there were twice as many patients enrolled in the IR arm as in the FCR arm, meaning that the rate of deaths in the FCR arm was fivefold higher than in the IR arm.

In a subgroup analysis of PFS, IR was superior to FCR regardless of patient age, sex, performance status, disease stage, or the presence or absence of the 11q23.3 deletion.

PFS was also significantly better with IR in patients with unmutated immunoglobulin heavy chain variable (IGHV) regions (HR 0.26, P less than .00001), but not in patients with mutated IGHV.*

Grade 3 or greater treatment-related adverse events occurred in 58.5% of patients in the IR arm, compared with 72.1% of patients in the FCR arm. Specific events that occurred significantly less often with IR included neutropenia (22.7% vs. 43.7%), anemia (2.6% vs. 12.0%), thrombocytopenia (2.9% vs. 13.9%), any infection (7.1% vs. 19.0%), and neutropenic fever (2.3% vs. 15.8%; P less than .001 for all comparisons).

Events that occurred more frequently with IR than FCR included atrial fibrillation (2.9% vs. 0%, P = .04), and hypertension (7.4% vs. 1.9%, P = .01).

Dr. Shanafelt acknowledged that one possible barrier to the IR regimen is cost; the monthly cost of ibrutinib maintenance is about $10,000, he said, although he noted that cost considerations were not studied in the trial.

“Future trials testing novel agent combinations to see if we can eliminate the need for chronic therapy should be pursued,” he said.

The trial was sponsored by the National Cancer Institute with additional support from Pharmacyclics. Dr. Shanafelt reported patents and royalties from the Mayo Clinic, and research funding from Celgene, GlaxoSmithKline, Genentech, Abbvie, Pharmacyclics, and Janssen.

SOURCE: Shanafelt TD et al. ASH 2018, Abstract LBA-4.

*Correction, 12/12/2018: An earlier version of this story misstated the P value in two comparisons.

SAN DIEGO – The combination of ibrutinib and rituximab was associated with a two-thirds reduction in chronic lymphocytic leukemia (CLL) progression, compared with standard chemoimmunotherapy in patients younger than 70 years old, interim results of a phase 3 randomized trial showed.

Among 529 patients with previously untreated, symptomatic CLL randomly assigned to ibrutinib-rituximab (IR) or to chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR), the IR regimen was associated with a 65% reduction in risk for disease progression, which was the trial’s primary endpoint.

The IR regimen was also associated with better overall survival out to 4 years of follow-up, reported Tait D. Shanafelt, MD, of Stanford (Calif.) University.

“This establishes ibrutinib-based therapy as the most effective treatment tested to date in this disease for untreated patients,” he said at a media briefing prior at the annual meeting of the American Society of Hematology.

The study results are likely to dethrone FCR as the most active chemoimmunotherapy regimen against CLL, Dr. Shanafelt said.

In the ECOG-ACRIN Cancer Research Group E1912 trial, 529 patients aged 70 or younger with previously untreated CLL were enrolled and randomly assigned on a 2:1 basis to either standard therapy with six cycles of FCR according to standard protocols (175 patients), or IR, with ibrutinib 420 mg daily for each cycle, and rituximab delivered 50 mg/m² intravenously on day 1 of cycle 2, and 325 mg/m² on day 2 of the same cycle, and 500 mg/m² on day 1 for all remaining cycles (354 patients).

From cycle 8 until progression, patients in the IR arm received daily ibrutinib 420 mg.

Dr. Shanafelt presented results from both an intention-to-treat analysis and a per-protocol analysis excluding 22 patients in the IR arm and 9 patients in the FCR arm who were randomized but later found not to meet eligibility criteria.

After a mean follow-up of 34 months, there were 37 PFS events in the IR arm, compared with 40 events in the FCR arm in an intention-to-treat analysis. The difference translated into a hazard ratio for progression of 0.35 with IR (P less than .00001).

The results were similar in the per-protocol analysis, with an HR of 0.32 favoring IR (P less than .00001).*

There were four deaths in the IR arm, compared with 10 in the FCR arm at the time of the data lock, translating into a hazard ratio (HR) for overall survival of 0.17 (P less than .0003) in the intention-to-treat analysis, and 0.13 in the per-protocol analysis (P less than .0001).

Dr. Shanafelt noted that although the overall number of deaths was relatively small, there were twice as many patients enrolled in the IR arm as in the FCR arm, meaning that the rate of deaths in the FCR arm was fivefold higher than in the IR arm.

In a subgroup analysis of PFS, IR was superior to FCR regardless of patient age, sex, performance status, disease stage, or the presence or absence of the 11q23.3 deletion.

PFS was also significantly better with IR in patients with unmutated immunoglobulin heavy chain variable (IGHV) regions (HR 0.26, P less than .00001), but not in patients with mutated IGHV.*

Grade 3 or greater treatment-related adverse events occurred in 58.5% of patients in the IR arm, compared with 72.1% of patients in the FCR arm. Specific events that occurred significantly less often with IR included neutropenia (22.7% vs. 43.7%), anemia (2.6% vs. 12.0%), thrombocytopenia (2.9% vs. 13.9%), any infection (7.1% vs. 19.0%), and neutropenic fever (2.3% vs. 15.8%; P less than .001 for all comparisons).

Events that occurred more frequently with IR than FCR included atrial fibrillation (2.9% vs. 0%, P = .04), and hypertension (7.4% vs. 1.9%, P = .01).

Dr. Shanafelt acknowledged that one possible barrier to the IR regimen is cost; the monthly cost of ibrutinib maintenance is about $10,000, he said, although he noted that cost considerations were not studied in the trial.

“Future trials testing novel agent combinations to see if we can eliminate the need for chronic therapy should be pursued,” he said.

The trial was sponsored by the National Cancer Institute with additional support from Pharmacyclics. Dr. Shanafelt reported patents and royalties from the Mayo Clinic, and research funding from Celgene, GlaxoSmithKline, Genentech, Abbvie, Pharmacyclics, and Janssen.

SOURCE: Shanafelt TD et al. ASH 2018, Abstract LBA-4.

*Correction, 12/12/2018: An earlier version of this story misstated the P value in two comparisons.

SAN DIEGO – The combination of ibrutinib and rituximab was associated with a two-thirds reduction in chronic lymphocytic leukemia (CLL) progression, compared with standard chemoimmunotherapy in patients younger than 70 years old, interim results of a phase 3 randomized trial showed.

Among 529 patients with previously untreated, symptomatic CLL randomly assigned to ibrutinib-rituximab (IR) or to chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR), the IR regimen was associated with a 65% reduction in risk for disease progression, which was the trial’s primary endpoint.

The IR regimen was also associated with better overall survival out to 4 years of follow-up, reported Tait D. Shanafelt, MD, of Stanford (Calif.) University.

“This establishes ibrutinib-based therapy as the most effective treatment tested to date in this disease for untreated patients,” he said at a media briefing prior at the annual meeting of the American Society of Hematology.

The study results are likely to dethrone FCR as the most active chemoimmunotherapy regimen against CLL, Dr. Shanafelt said.

In the ECOG-ACRIN Cancer Research Group E1912 trial, 529 patients aged 70 or younger with previously untreated CLL were enrolled and randomly assigned on a 2:1 basis to either standard therapy with six cycles of FCR according to standard protocols (175 patients), or IR, with ibrutinib 420 mg daily for each cycle, and rituximab delivered 50 mg/m² intravenously on day 1 of cycle 2, and 325 mg/m² on day 2 of the same cycle, and 500 mg/m² on day 1 for all remaining cycles (354 patients).

From cycle 8 until progression, patients in the IR arm received daily ibrutinib 420 mg.

Dr. Shanafelt presented results from both an intention-to-treat analysis and a per-protocol analysis excluding 22 patients in the IR arm and 9 patients in the FCR arm who were randomized but later found not to meet eligibility criteria.

After a mean follow-up of 34 months, there were 37 PFS events in the IR arm, compared with 40 events in the FCR arm in an intention-to-treat analysis. The difference translated into a hazard ratio for progression of 0.35 with IR (P less than .00001).

The results were similar in the per-protocol analysis, with an HR of 0.32 favoring IR (P less than .00001).*

There were four deaths in the IR arm, compared with 10 in the FCR arm at the time of the data lock, translating into a hazard ratio (HR) for overall survival of 0.17 (P less than .0003) in the intention-to-treat analysis, and 0.13 in the per-protocol analysis (P less than .0001).

Dr. Shanafelt noted that although the overall number of deaths was relatively small, there were twice as many patients enrolled in the IR arm as in the FCR arm, meaning that the rate of deaths in the FCR arm was fivefold higher than in the IR arm.

In a subgroup analysis of PFS, IR was superior to FCR regardless of patient age, sex, performance status, disease stage, or the presence or absence of the 11q23.3 deletion.

PFS was also significantly better with IR in patients with unmutated immunoglobulin heavy chain variable (IGHV) regions (HR 0.26, P less than .00001), but not in patients with mutated IGHV.*

Grade 3 or greater treatment-related adverse events occurred in 58.5% of patients in the IR arm, compared with 72.1% of patients in the FCR arm. Specific events that occurred significantly less often with IR included neutropenia (22.7% vs. 43.7%), anemia (2.6% vs. 12.0%), thrombocytopenia (2.9% vs. 13.9%), any infection (7.1% vs. 19.0%), and neutropenic fever (2.3% vs. 15.8%; P less than .001 for all comparisons).

Events that occurred more frequently with IR than FCR included atrial fibrillation (2.9% vs. 0%, P = .04), and hypertension (7.4% vs. 1.9%, P = .01).

Dr. Shanafelt acknowledged that one possible barrier to the IR regimen is cost; the monthly cost of ibrutinib maintenance is about $10,000, he said, although he noted that cost considerations were not studied in the trial.

“Future trials testing novel agent combinations to see if we can eliminate the need for chronic therapy should be pursued,” he said.

The trial was sponsored by the National Cancer Institute with additional support from Pharmacyclics. Dr. Shanafelt reported patents and royalties from the Mayo Clinic, and research funding from Celgene, GlaxoSmithKline, Genentech, Abbvie, Pharmacyclics, and Janssen.

SOURCE: Shanafelt TD et al. ASH 2018, Abstract LBA-4.

*Correction, 12/12/2018: An earlier version of this story misstated the P value in two comparisons.

SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.

Courtesy American Society of Hematology

“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”

Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”

Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.

In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.

In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”

When asked how his care could have been improved, Mr. Brokaw said there could have been more focus on the physical effects of multiple myeloma on his body. “There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”

At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”

He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”

“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.

Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”

SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.

Courtesy American Society of Hematology

“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”

Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”

Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.

In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.

In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”

When asked how his care could have been improved, Mr. Brokaw said there could have been more focus on the physical effects of multiple myeloma on his body. “There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”

At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”

He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”

“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.

Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”

SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.

Courtesy American Society of Hematology

“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”

Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”

Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.

In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.

In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”

When asked how his care could have been improved, Mr. Brokaw said there could have been more focus on the physical effects of multiple myeloma on his body. “There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”

At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”

He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”

“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.

Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”

LAS VEGAS – Vaginal trial of labor is safe after myomectomy, at least if the uterine cavity wasn’t entered, according to investigators from Northwestern University, Chicago.

M. Alexander Otto/MDedge News

The American College of Obstetricians and Gynecologists lists prior myomectomy as a medically-indicated reason for delivery before 39 weeks. The advice reflects a traditional concern that uterine scars will rupture during labor, with potentially devastating consequences for both mother and infant.

Reviews have put the risk at less than 1%, so ob.gyns. have shied away from ACOG’s blanket advice and now use uterine-cavity entry during myomectomy as their talisman for deciding whether or not to offer women vaginal delivery. The assumption is that uterine entry makes rupture more likely, but there’s not much evidence to support that idea, and it’s become clear in recent years that women who have a significant full-thickness insult to uterine integrity – a prior C-section – can usually deliver vaginally with no problem. In short, the uterus seems to have a remarkable ability to heal itself.

Even so, there are still ob.gyns. who pressure women into having premature babies if they’ve had a fibroid removed even without cavity entry. Barring additional indications, that doesn’t happen anymore at Northwestern University, said lead investigator Nathan King, MD, an ob.gyn. resident at the university.

The Northwestern team wanted to clear the fog. What they found adds to “literature that demonstrates the overall low risk of undergoing VTOL [vaginal trial of labor] after a prior myomectomy. We hope providers will feel more comfortable talking to their patients about delivery [options] and the success of VTOL after myomectomy,” Dr. King said at a meeting sponsored by AAGL.*

He and his team analyzed pregnancy outcomes in 112 women who had a live birth after non–cavity-entering myomectomies. Forty-nine women (44%) were allowed to undergo VTOL; 63 others had C-sections, most at term.

Thirty-two VTOL women (65%) had vaginal deliveries, a success rate similar to that of labor after C-section. There was just one uterine rupture in the VTOL group, for an incidence of 2%, which also was comparable to the rupture risk after a low-transverse C-section.

The rupture was discovered after spontaneous vaginal delivery, and an addressed by laparotomy. Both mother and infant were fine.

Adverse events were less likely in the VTOL group, regardless if they ultimately delivered vaginally or by C-section. The lower adverse event rate was driven by fewer postpartum hemorrhages (odds ratio, 0.441, 95% confidence interval, 0.2002-0.9722, P = .042).

There were no demographic difference between women who were allowed to undergo VTOL and those who were not. For most, it was their first delivery.

Women who had their uterine cavities entered during myomectomy weren’t allowed to undergo VTOL at Northwestern, and were not included in the analysis. Also, the study did not include women who became pregnant after myomectomy, but did not have a live delivery. The incidence of uterine rupture among them, if any, was not reported.

There was no external funding for the work, and Dr. King didn’t have any disclosures.

[email protected]

SOURCE: King N et al. 2018 AAGL Global Congress, Abstract 162.

*Correction, 12/11/2018: An earlier version of this story misstated the name of the meeting sponsor. It is AAGL.
 

LAS VEGAS – Vaginal trial of labor is safe after myomectomy, at least if the uterine cavity wasn’t entered, according to investigators from Northwestern University, Chicago.

M. Alexander Otto/MDedge News

The American College of Obstetricians and Gynecologists lists prior myomectomy as a medically-indicated reason for delivery before 39 weeks. The advice reflects a traditional concern that uterine scars will rupture during labor, with potentially devastating consequences for both mother and infant.

Reviews have put the risk at less than 1%, so ob.gyns. have shied away from ACOG’s blanket advice and now use uterine-cavity entry during myomectomy as their talisman for deciding whether or not to offer women vaginal delivery. The assumption is that uterine entry makes rupture more likely, but there’s not much evidence to support that idea, and it’s become clear in recent years that women who have a significant full-thickness insult to uterine integrity – a prior C-section – can usually deliver vaginally with no problem. In short, the uterus seems to have a remarkable ability to heal itself.

Even so, there are still ob.gyns. who pressure women into having premature babies if they’ve had a fibroid removed even without cavity entry. Barring additional indications, that doesn’t happen anymore at Northwestern University, said lead investigator Nathan King, MD, an ob.gyn. resident at the university.

The Northwestern team wanted to clear the fog. What they found adds to “literature that demonstrates the overall low risk of undergoing VTOL [vaginal trial of labor] after a prior myomectomy. We hope providers will feel more comfortable talking to their patients about delivery [options] and the success of VTOL after myomectomy,” Dr. King said at a meeting sponsored by AAGL.*

He and his team analyzed pregnancy outcomes in 112 women who had a live birth after non–cavity-entering myomectomies. Forty-nine women (44%) were allowed to undergo VTOL; 63 others had C-sections, most at term.

Thirty-two VTOL women (65%) had vaginal deliveries, a success rate similar to that of labor after C-section. There was just one uterine rupture in the VTOL group, for an incidence of 2%, which also was comparable to the rupture risk after a low-transverse C-section.

The rupture was discovered after spontaneous vaginal delivery, and an addressed by laparotomy. Both mother and infant were fine.

Adverse events were less likely in the VTOL group, regardless if they ultimately delivered vaginally or by C-section. The lower adverse event rate was driven by fewer postpartum hemorrhages (odds ratio, 0.441, 95% confidence interval, 0.2002-0.9722, P = .042).

There were no demographic difference between women who were allowed to undergo VTOL and those who were not. For most, it was their first delivery.

Women who had their uterine cavities entered during myomectomy weren’t allowed to undergo VTOL at Northwestern, and were not included in the analysis. Also, the study did not include women who became pregnant after myomectomy, but did not have a live delivery. The incidence of uterine rupture among them, if any, was not reported.

There was no external funding for the work, and Dr. King didn’t have any disclosures.

[email protected]

SOURCE: King N et al. 2018 AAGL Global Congress, Abstract 162.

*Correction, 12/11/2018: An earlier version of this story misstated the name of the meeting sponsor. It is AAGL.
 

LAS VEGAS – Vaginal trial of labor is safe after myomectomy, at least if the uterine cavity wasn’t entered, according to investigators from Northwestern University, Chicago.

M. Alexander Otto/MDedge News

The American College of Obstetricians and Gynecologists lists prior myomectomy as a medically-indicated reason for delivery before 39 weeks. The advice reflects a traditional concern that uterine scars will rupture during labor, with potentially devastating consequences for both mother and infant.

Reviews have put the risk at less than 1%, so ob.gyns. have shied away from ACOG’s blanket advice and now use uterine-cavity entry during myomectomy as their talisman for deciding whether or not to offer women vaginal delivery. The assumption is that uterine entry makes rupture more likely, but there’s not much evidence to support that idea, and it’s become clear in recent years that women who have a significant full-thickness insult to uterine integrity – a prior C-section – can usually deliver vaginally with no problem. In short, the uterus seems to have a remarkable ability to heal itself.

Even so, there are still ob.gyns. who pressure women into having premature babies if they’ve had a fibroid removed even without cavity entry. Barring additional indications, that doesn’t happen anymore at Northwestern University, said lead investigator Nathan King, MD, an ob.gyn. resident at the university.

The Northwestern team wanted to clear the fog. What they found adds to “literature that demonstrates the overall low risk of undergoing VTOL [vaginal trial of labor] after a prior myomectomy. We hope providers will feel more comfortable talking to their patients about delivery [options] and the success of VTOL after myomectomy,” Dr. King said at a meeting sponsored by AAGL.*

He and his team analyzed pregnancy outcomes in 112 women who had a live birth after non–cavity-entering myomectomies. Forty-nine women (44%) were allowed to undergo VTOL; 63 others had C-sections, most at term.

Thirty-two VTOL women (65%) had vaginal deliveries, a success rate similar to that of labor after C-section. There was just one uterine rupture in the VTOL group, for an incidence of 2%, which also was comparable to the rupture risk after a low-transverse C-section.

The rupture was discovered after spontaneous vaginal delivery, and an addressed by laparotomy. Both mother and infant were fine.

Adverse events were less likely in the VTOL group, regardless if they ultimately delivered vaginally or by C-section. The lower adverse event rate was driven by fewer postpartum hemorrhages (odds ratio, 0.441, 95% confidence interval, 0.2002-0.9722, P = .042).

There were no demographic difference between women who were allowed to undergo VTOL and those who were not. For most, it was their first delivery.

Women who had their uterine cavities entered during myomectomy weren’t allowed to undergo VTOL at Northwestern, and were not included in the analysis. Also, the study did not include women who became pregnant after myomectomy, but did not have a live delivery. The incidence of uterine rupture among them, if any, was not reported.

There was no external funding for the work, and Dr. King didn’t have any disclosures.

[email protected]

SOURCE: King N et al. 2018 AAGL Global Congress, Abstract 162.

*Correction, 12/11/2018: An earlier version of this story misstated the name of the meeting sponsor. It is AAGL.
 

Whenever the principles of effective medical consultation are discussed, a classic article published in 1983 by Lee Goldman et al. is invariably referenced. In the “Ten Commandments for Effective Consultation,” Goldman argued that internists should “determine the question, establish urgency, look for yourself, be as brief as appropriate, be specific, provide contingency plans, honor thy turf, teach with tact, provide direct personal contact, and follow up.”¹ If these Ten Commandments were followed, then the consultation would be more effective and satisfactory for both the consultant and the referring provider. However, with the advent of comanagement in 1994 where internists and surgeons have a “shared responsibility and accountability,”² there has been a shift, and the once-concrete definitions of a specific reason for consult and the nature of “turf” have become blurred. Since 1994, the use of medical consultation and comanagement has skyrocketed, and today, more than 50% of surgical patients have a medical consultation or comanagement.³ This may be due to increased time pressures on surgeons and better outcomes of comanaged patients (eg, fewer postoperative complications, fewer transfers to an intensive care unit for acute medical deterioration, and increased likelihood to discharge to home).⁴

Medical management of surgical patients in the hospital involves a different skill set than that required to manage general medical patients. Accordingly, in 2012, the Accreditation Council for Graduate Medical Education (ACGME) made medical consultation and perioperative care an End of Training Entrustable Professional Activities and ACGME subcompetency. Earlier this year, a nationwide perioperative curriculum for graduate medical education was consisting of eight objective and core topic modules and pretest/posttest questions selected from SHMConsults.com, including assessment and management of perioperative cardiac and pulmonary risk and management of diabetes, perioperative fever, and anticoagulants. Trainees were assessed using the multiple-choice questions, observed mini-cex, and written evaluation of a consultation report. Despite this encouraging development of curricula and competencies for trainees, there are still important gaps in our knowledge of basic patterns for consultation practices. For example, the type of patients and medical conditions currently encountered on our medical consultation and comanagement services had been previously unknown.

In the December issue of the Journal of Hospital Medicine, Wang et al. answer this question through the first cross-sectional multicenter prospective survey to examine medical consultation/comanagement practices since observational studies in the 1970-1990s.⁶ In a sample of 1,264 consultation requests from 11 academic medical centers over four two-week periods from July 2014 through July 2015, they found that the most common requests for consultation were medical management/comanagement, preoperative evaluation, blood pressure management, and other common postoperative complications, including postoperative atrial fibrillation, heart failure, renal failure, hyponatremia, anemia, hypoxia, and altered mental status.⁹ The majority of referrals were from orthopedic surgery and neurosurgery. They also found that medical consultants and comanagers provided comprehensive evaluations where more than a third of encounters addressed issues that were not stated in the initial reason for consult (RFC) and that consultants addressed more than two RFCs per encounter.⁹

These findings illustrate the paradigm shift of medical consultation focusing on a single specific question to addressing and optimizing the entire patient. This shift toward a broader, more open-ended reason for consultation may present some challenges such as “dumping” where referring surgeons and other specialists signoff their patients after surgery is completed, with internists processing the surgeons’ patients through the hospitalization. These challenges can be mitigated with predefined comanagement agreements with clearly defined roles and collaborative professional relationships.

Nonetheless, given the recent developments in curricula and training competencies mentioned above, internists are better equipped than ever before to put everything together and take care of the medical conditions of the increasingly complex and older surgical patient. For example, if one is consulted to see a patient for postoperative hypertension, it is difficult to not address the patient’s blood sugars in the 300s, lack of venous thromboembolism prophylaxis, delirium, acute renal failure, and acute blood loss anemia. The authors are correct to assert it is critically important to ensure that this input is desired by the referring physician either via verbal communication or comanagement agreements.

The findings of Wang et al. suggest some important future steps in medical consultation to ensure that our trainees and colleagues are prepared to take care of the entire patient regardless of whether the patient is on a consultant or comanagement agreement. This study shows that trainees are exposed to a diverse clinical experience on our medical consultation and comanagement services, which is in accordance with the objectives, assessment tools, and modules of the nationwide curriculum. It is likely that comanagement services will continue to expand as more of our medically complex patients will need either elective or emergency surgeries and surgeons have become less comfortable managing these patients on their own. We also may be asked to participate in quality improvement initiatives in the management of surgical patients, including the “perioperative surgical home programs,” where physicians work on a patient-centered approach to the surgical patient using evidence-based standard clinical care pathways and transitions from before surgery to postdischarge.⁷ We should share our experiences in quality improvement and the patient-centered medical home to ensure that our patients are optimized for surgery and beyond. As Lee Goldman et al. stated in the “Ten Commandments for Effective Consultations,¹” consultative medicine is an important part of an internal medicine practice. Today, more than ever, the consultant or comanagement role or roles need to be carefully defined and clear communication and follow-up are important.

Whenever the principles of effective medical consultation are discussed, a classic article published in 1983 by Lee Goldman et al. is invariably referenced. In the “Ten Commandments for Effective Consultation,” Goldman argued that internists should “determine the question, establish urgency, look for yourself, be as brief as appropriate, be specific, provide contingency plans, honor thy turf, teach with tact, provide direct personal contact, and follow up.”¹ If these Ten Commandments were followed, then the consultation would be more effective and satisfactory for both the consultant and the referring provider. However, with the advent of comanagement in 1994 where internists and surgeons have a “shared responsibility and accountability,”² there has been a shift, and the once-concrete definitions of a specific reason for consult and the nature of “turf” have become blurred. Since 1994, the use of medical consultation and comanagement has skyrocketed, and today, more than 50% of surgical patients have a medical consultation or comanagement.³ This may be due to increased time pressures on surgeons and better outcomes of comanaged patients (eg, fewer postoperative complications, fewer transfers to an intensive care unit for acute medical deterioration, and increased likelihood to discharge to home).⁴

Medical management of surgical patients in the hospital involves a different skill set than that required to manage general medical patients. Accordingly, in 2012, the Accreditation Council for Graduate Medical Education (ACGME) made medical consultation and perioperative care an End of Training Entrustable Professional Activities and ACGME subcompetency. Earlier this year, a nationwide perioperative curriculum for graduate medical education was consisting of eight objective and core topic modules and pretest/posttest questions selected from SHMConsults.com, including assessment and management of perioperative cardiac and pulmonary risk and management of diabetes, perioperative fever, and anticoagulants. Trainees were assessed using the multiple-choice questions, observed mini-cex, and written evaluation of a consultation report. Despite this encouraging development of curricula and competencies for trainees, there are still important gaps in our knowledge of basic patterns for consultation practices. For example, the type of patients and medical conditions currently encountered on our medical consultation and comanagement services had been previously unknown.

In the December issue of the Journal of Hospital Medicine, Wang et al. answer this question through the first cross-sectional multicenter prospective survey to examine medical consultation/comanagement practices since observational studies in the 1970-1990s.⁶ In a sample of 1,264 consultation requests from 11 academic medical centers over four two-week periods from July 2014 through July 2015, they found that the most common requests for consultation were medical management/comanagement, preoperative evaluation, blood pressure management, and other common postoperative complications, including postoperative atrial fibrillation, heart failure, renal failure, hyponatremia, anemia, hypoxia, and altered mental status.⁹ The majority of referrals were from orthopedic surgery and neurosurgery. They also found that medical consultants and comanagers provided comprehensive evaluations where more than a third of encounters addressed issues that were not stated in the initial reason for consult (RFC) and that consultants addressed more than two RFCs per encounter.⁹

These findings illustrate the paradigm shift of medical consultation focusing on a single specific question to addressing and optimizing the entire patient. This shift toward a broader, more open-ended reason for consultation may present some challenges such as “dumping” where referring surgeons and other specialists signoff their patients after surgery is completed, with internists processing the surgeons’ patients through the hospitalization. These challenges can be mitigated with predefined comanagement agreements with clearly defined roles and collaborative professional relationships.

Nonetheless, given the recent developments in curricula and training competencies mentioned above, internists are better equipped than ever before to put everything together and take care of the medical conditions of the increasingly complex and older surgical patient. For example, if one is consulted to see a patient for postoperative hypertension, it is difficult to not address the patient’s blood sugars in the 300s, lack of venous thromboembolism prophylaxis, delirium, acute renal failure, and acute blood loss anemia. The authors are correct to assert it is critically important to ensure that this input is desired by the referring physician either via verbal communication or comanagement agreements.

The findings of Wang et al. suggest some important future steps in medical consultation to ensure that our trainees and colleagues are prepared to take care of the entire patient regardless of whether the patient is on a consultant or comanagement agreement. This study shows that trainees are exposed to a diverse clinical experience on our medical consultation and comanagement services, which is in accordance with the objectives, assessment tools, and modules of the nationwide curriculum. It is likely that comanagement services will continue to expand as more of our medically complex patients will need either elective or emergency surgeries and surgeons have become less comfortable managing these patients on their own. We also may be asked to participate in quality improvement initiatives in the management of surgical patients, including the “perioperative surgical home programs,” where physicians work on a patient-centered approach to the surgical patient using evidence-based standard clinical care pathways and transitions from before surgery to postdischarge.⁷ We should share our experiences in quality improvement and the patient-centered medical home to ensure that our patients are optimized for surgery and beyond. As Lee Goldman et al. stated in the “Ten Commandments for Effective Consultations,¹” consultative medicine is an important part of an internal medicine practice. Today, more than ever, the consultant or comanagement role or roles need to be carefully defined and clear communication and follow-up are important.

Whenever the principles of effective medical consultation are discussed, a classic article published in 1983 by Lee Goldman et al. is invariably referenced. In the “Ten Commandments for Effective Consultation,” Goldman argued that internists should “determine the question, establish urgency, look for yourself, be as brief as appropriate, be specific, provide contingency plans, honor thy turf, teach with tact, provide direct personal contact, and follow up.”¹ If these Ten Commandments were followed, then the consultation would be more effective and satisfactory for both the consultant and the referring provider. However, with the advent of comanagement in 1994 where internists and surgeons have a “shared responsibility and accountability,”² there has been a shift, and the once-concrete definitions of a specific reason for consult and the nature of “turf” have become blurred. Since 1994, the use of medical consultation and comanagement has skyrocketed, and today, more than 50% of surgical patients have a medical consultation or comanagement.³ This may be due to increased time pressures on surgeons and better outcomes of comanaged patients (eg, fewer postoperative complications, fewer transfers to an intensive care unit for acute medical deterioration, and increased likelihood to discharge to home).⁴

Medical management of surgical patients in the hospital involves a different skill set than that required to manage general medical patients. Accordingly, in 2012, the Accreditation Council for Graduate Medical Education (ACGME) made medical consultation and perioperative care an End of Training Entrustable Professional Activities and ACGME subcompetency. Earlier this year, a nationwide perioperative curriculum for graduate medical education was consisting of eight objective and core topic modules and pretest/posttest questions selected from SHMConsults.com, including assessment and management of perioperative cardiac and pulmonary risk and management of diabetes, perioperative fever, and anticoagulants. Trainees were assessed using the multiple-choice questions, observed mini-cex, and written evaluation of a consultation report. Despite this encouraging development of curricula and competencies for trainees, there are still important gaps in our knowledge of basic patterns for consultation practices. For example, the type of patients and medical conditions currently encountered on our medical consultation and comanagement services had been previously unknown.

In the December issue of the Journal of Hospital Medicine, Wang et al. answer this question through the first cross-sectional multicenter prospective survey to examine medical consultation/comanagement practices since observational studies in the 1970-1990s.⁶ In a sample of 1,264 consultation requests from 11 academic medical centers over four two-week periods from July 2014 through July 2015, they found that the most common requests for consultation were medical management/comanagement, preoperative evaluation, blood pressure management, and other common postoperative complications, including postoperative atrial fibrillation, heart failure, renal failure, hyponatremia, anemia, hypoxia, and altered mental status.⁹ The majority of referrals were from orthopedic surgery and neurosurgery. They also found that medical consultants and comanagers provided comprehensive evaluations where more than a third of encounters addressed issues that were not stated in the initial reason for consult (RFC) and that consultants addressed more than two RFCs per encounter.⁹

These findings illustrate the paradigm shift of medical consultation focusing on a single specific question to addressing and optimizing the entire patient. This shift toward a broader, more open-ended reason for consultation may present some challenges such as “dumping” where referring surgeons and other specialists signoff their patients after surgery is completed, with internists processing the surgeons’ patients through the hospitalization. These challenges can be mitigated with predefined comanagement agreements with clearly defined roles and collaborative professional relationships.

Nonetheless, given the recent developments in curricula and training competencies mentioned above, internists are better equipped than ever before to put everything together and take care of the medical conditions of the increasingly complex and older surgical patient. For example, if one is consulted to see a patient for postoperative hypertension, it is difficult to not address the patient’s blood sugars in the 300s, lack of venous thromboembolism prophylaxis, delirium, acute renal failure, and acute blood loss anemia. The authors are correct to assert it is critically important to ensure that this input is desired by the referring physician either via verbal communication or comanagement agreements.

The findings of Wang et al. suggest some important future steps in medical consultation to ensure that our trainees and colleagues are prepared to take care of the entire patient regardless of whether the patient is on a consultant or comanagement agreement. This study shows that trainees are exposed to a diverse clinical experience on our medical consultation and comanagement services, which is in accordance with the objectives, assessment tools, and modules of the nationwide curriculum. It is likely that comanagement services will continue to expand as more of our medically complex patients will need either elective or emergency surgeries and surgeons have become less comfortable managing these patients on their own. We also may be asked to participate in quality improvement initiatives in the management of surgical patients, including the “perioperative surgical home programs,” where physicians work on a patient-centered approach to the surgical patient using evidence-based standard clinical care pathways and transitions from before surgery to postdischarge.⁷ We should share our experiences in quality improvement and the patient-centered medical home to ensure that our patients are optimized for surgery and beyond. As Lee Goldman et al. stated in the “Ten Commandments for Effective Consultations,¹” consultative medicine is an important part of an internal medicine practice. Today, more than ever, the consultant or comanagement role or roles need to be carefully defined and clear communication and follow-up are important.

Decreased insulin clearance may be the first step on the path to insulin resistance. Also today, tender joint count may confound assessment of RA inflammation, common AEDs confer moderately increased risk of major congenital malformations, and the ACR and the NPF unveil new treatment guidelines for psoriatic arthritis.

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Apple Podcasts

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Decreased insulin clearance may be the first step on the path to insulin resistance. Also today, tender joint count may confound assessment of RA inflammation, common AEDs confer moderately increased risk of major congenital malformations, and the ACR and the NPF unveil new treatment guidelines for psoriatic arthritis.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Decreased insulin clearance may be the first step on the path to insulin resistance. Also today, tender joint count may confound assessment of RA inflammation, common AEDs confer moderately increased risk of major congenital malformations, and the ACR and the NPF unveil new treatment guidelines for psoriatic arthritis.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

© ASH/Rodney White 2018

SAN DIEGO—A phase 1 study suggests lymphodepletion can improve the efficacy of CD30-directed chimeric antigen receptor (CAR) T-cell therapy in patients with Hodgkin lymphoma (HL).

Researchers observed improved responses in HL patients treated with fludarabine and cyclophosphamide prior to CD30.CAR T-cell therapy.

This lymphodepleting regimen was also associated with increased toxicity, compared to no lymphodepletion. However, researchers consider the regimen safe.

Carlos A. Ramos, MD, of Baylor College of Medicine in Houston, Texas, presented these results at the 2018 ASH Annual Meeting (abstract 680*).

Without lymphodepletion

Dr. Ramos first discussed a previous phase 1 trial (NCT01316146), which was published in The Journal of Clinical Investigation in 2017.

In this trial, he and his colleagues had tested CD30.CAR T-cell therapy in patients with relapsed/refractory, CD30+ HL or T-cell non-Hodgkin lymphoma. None of these patients underwent lymphodepletion.

There were no dose-limiting toxicities in this trial—including no neurotoxicity or cytokine release syndrome—but responses were “limited,” according to Dr. Ramos.

Three patients achieved a complete response (CR), three had stable disease, and three progressed.

“Although we saw no significant toxicities and some good clinical responses . . ., the bottom line is that the responses were still quite limited, with several patients having, at most, stable disease or progressive disease,” Dr. Ramos said.

With lymphodepletion

Results from the previous trial prompted Dr. Ramos and his colleagues to conduct the RELY-30 trial (NCT02917083) and investigate whether lymphodepletion would improve responses to CD30.CAR T-cell therapy.

Thus far, 11 patients have been treated on this trial. All had relapsed, CD30+ HL at baseline. Six patients are male, and their median age at baseline was 30 (range, 17-69).

The patients had a median of 5 prior treatments (range, 2-9). This included PD-1 inhibitors (n=10), brentuximab vedotin (n=8), and transplant (n=6).

All patients received lymphodepletion with cyclophosphamide at 500 mg/m² and fludarabine at 30 mg/m² daily for 3 days. They then received CD30.CAR T-cell therapy at 2×10⁷ cells/m² or 1×10⁸ cells/m².

Dr. Ramos noted that CD30.CAR T-cell expansion was dose-dependent and increased by lymphodepleting chemotherapy.

“The peak expansion is much higher [with lymphodepletion], probably in the order of two to three logs higher than what we see without lymphodepleting chemotherapy,” he said. “So chemotherapy makes a difference.”

Increased CD30.CAR T-cell expansion was associated with improved response. Of the nine evaluable patients, six achieved a CR, and three progressed.

Four complete responders were still in CR at last follow-up, one of them for more than a year. However, two complete responders ultimately progressed.

In addition to improved responses, the researchers observed increased toxicity in this trial. Dr. Ramos said some of these toxicities are “probably attributable” to the lymphodepleting chemotherapy.

Toxicities included grade 1 cytokine release syndrome (no tocilizumab required), maculopapular rash, transient cytopenias, nausea, vomiting, and alopecia.

Dr. Ramos said these results suggest adoptive transfer of CD30.CAR T cells is “safe, even with chemotherapy.”

He noted that the duration of response with this treatment is unknown, but trial enrollment and follow-up are ongoing.

RELY-30 was sponsored by Baylor College of Medicine. Dr. Ramos reported relationships with Novartis, Celgene, Bluebird Bio, and Tessa Therapeutics.

*Data in the abstract differ from the presentation.

© ASH/Rodney White 2018

SAN DIEGO—A phase 1 study suggests lymphodepletion can improve the efficacy of CD30-directed chimeric antigen receptor (CAR) T-cell therapy in patients with Hodgkin lymphoma (HL).

Researchers observed improved responses in HL patients treated with fludarabine and cyclophosphamide prior to CD30.CAR T-cell therapy.

This lymphodepleting regimen was also associated with increased toxicity, compared to no lymphodepletion. However, researchers consider the regimen safe.

Carlos A. Ramos, MD, of Baylor College of Medicine in Houston, Texas, presented these results at the 2018 ASH Annual Meeting (abstract 680*).

Without lymphodepletion

Dr. Ramos first discussed a previous phase 1 trial (NCT01316146), which was published in The Journal of Clinical Investigation in 2017.

In this trial, he and his colleagues had tested CD30.CAR T-cell therapy in patients with relapsed/refractory, CD30+ HL or T-cell non-Hodgkin lymphoma. None of these patients underwent lymphodepletion.

There were no dose-limiting toxicities in this trial—including no neurotoxicity or cytokine release syndrome—but responses were “limited,” according to Dr. Ramos.

Three patients achieved a complete response (CR), three had stable disease, and three progressed.

“Although we saw no significant toxicities and some good clinical responses . . ., the bottom line is that the responses were still quite limited, with several patients having, at most, stable disease or progressive disease,” Dr. Ramos said.

With lymphodepletion

Results from the previous trial prompted Dr. Ramos and his colleagues to conduct the RELY-30 trial (NCT02917083) and investigate whether lymphodepletion would improve responses to CD30.CAR T-cell therapy.

Thus far, 11 patients have been treated on this trial. All had relapsed, CD30+ HL at baseline. Six patients are male, and their median age at baseline was 30 (range, 17-69).

The patients had a median of 5 prior treatments (range, 2-9). This included PD-1 inhibitors (n=10), brentuximab vedotin (n=8), and transplant (n=6).

All patients received lymphodepletion with cyclophosphamide at 500 mg/m² and fludarabine at 30 mg/m² daily for 3 days. They then received CD30.CAR T-cell therapy at 2×10⁷ cells/m² or 1×10⁸ cells/m².

Dr. Ramos noted that CD30.CAR T-cell expansion was dose-dependent and increased by lymphodepleting chemotherapy.

“The peak expansion is much higher [with lymphodepletion], probably in the order of two to three logs higher than what we see without lymphodepleting chemotherapy,” he said. “So chemotherapy makes a difference.”

Increased CD30.CAR T-cell expansion was associated with improved response. Of the nine evaluable patients, six achieved a CR, and three progressed.

Four complete responders were still in CR at last follow-up, one of them for more than a year. However, two complete responders ultimately progressed.

In addition to improved responses, the researchers observed increased toxicity in this trial. Dr. Ramos said some of these toxicities are “probably attributable” to the lymphodepleting chemotherapy.

Toxicities included grade 1 cytokine release syndrome (no tocilizumab required), maculopapular rash, transient cytopenias, nausea, vomiting, and alopecia.

Dr. Ramos said these results suggest adoptive transfer of CD30.CAR T cells is “safe, even with chemotherapy.”

He noted that the duration of response with this treatment is unknown, but trial enrollment and follow-up are ongoing.

RELY-30 was sponsored by Baylor College of Medicine. Dr. Ramos reported relationships with Novartis, Celgene, Bluebird Bio, and Tessa Therapeutics.

*Data in the abstract differ from the presentation.

© ASH/Rodney White 2018

SAN DIEGO—A phase 1 study suggests lymphodepletion can improve the efficacy of CD30-directed chimeric antigen receptor (CAR) T-cell therapy in patients with Hodgkin lymphoma (HL).

Researchers observed improved responses in HL patients treated with fludarabine and cyclophosphamide prior to CD30.CAR T-cell therapy.

This lymphodepleting regimen was also associated with increased toxicity, compared to no lymphodepletion. However, researchers consider the regimen safe.

Carlos A. Ramos, MD, of Baylor College of Medicine in Houston, Texas, presented these results at the 2018 ASH Annual Meeting (abstract 680*).

Without lymphodepletion

Dr. Ramos first discussed a previous phase 1 trial (NCT01316146), which was published in The Journal of Clinical Investigation in 2017.

In this trial, he and his colleagues had tested CD30.CAR T-cell therapy in patients with relapsed/refractory, CD30+ HL or T-cell non-Hodgkin lymphoma. None of these patients underwent lymphodepletion.

There were no dose-limiting toxicities in this trial—including no neurotoxicity or cytokine release syndrome—but responses were “limited,” according to Dr. Ramos.

Three patients achieved a complete response (CR), three had stable disease, and three progressed.

“Although we saw no significant toxicities and some good clinical responses . . ., the bottom line is that the responses were still quite limited, with several patients having, at most, stable disease or progressive disease,” Dr. Ramos said.

With lymphodepletion

Results from the previous trial prompted Dr. Ramos and his colleagues to conduct the RELY-30 trial (NCT02917083) and investigate whether lymphodepletion would improve responses to CD30.CAR T-cell therapy.

Thus far, 11 patients have been treated on this trial. All had relapsed, CD30+ HL at baseline. Six patients are male, and their median age at baseline was 30 (range, 17-69).

The patients had a median of 5 prior treatments (range, 2-9). This included PD-1 inhibitors (n=10), brentuximab vedotin (n=8), and transplant (n=6).

All patients received lymphodepletion with cyclophosphamide at 500 mg/m² and fludarabine at 30 mg/m² daily for 3 days. They then received CD30.CAR T-cell therapy at 2×10⁷ cells/m² or 1×10⁸ cells/m².

Dr. Ramos noted that CD30.CAR T-cell expansion was dose-dependent and increased by lymphodepleting chemotherapy.

“The peak expansion is much higher [with lymphodepletion], probably in the order of two to three logs higher than what we see without lymphodepleting chemotherapy,” he said. “So chemotherapy makes a difference.”

Increased CD30.CAR T-cell expansion was associated with improved response. Of the nine evaluable patients, six achieved a CR, and three progressed.

Four complete responders were still in CR at last follow-up, one of them for more than a year. However, two complete responders ultimately progressed.

In addition to improved responses, the researchers observed increased toxicity in this trial. Dr. Ramos said some of these toxicities are “probably attributable” to the lymphodepleting chemotherapy.

Toxicities included grade 1 cytokine release syndrome (no tocilizumab required), maculopapular rash, transient cytopenias, nausea, vomiting, and alopecia.

Dr. Ramos said these results suggest adoptive transfer of CD30.CAR T cells is “safe, even with chemotherapy.”

He noted that the duration of response with this treatment is unknown, but trial enrollment and follow-up are ongoing.

RELY-30 was sponsored by Baylor College of Medicine. Dr. Ramos reported relationships with Novartis, Celgene, Bluebird Bio, and Tessa Therapeutics.

*Data in the abstract differ from the presentation.