Jan Dyer

As more people are surviving breast cancer, more will be given bisphosphonate (BP) for bone metastases—and may be at risk for treatment adverse effects, such as atypical femoral fracture (AFF). Clinicians from Royal Victoria Hospital, Belfast, United Kingdom, describe what they learned in the first reported case of AFF caused by daily ibandronate.

The patient, a 55-year-old woman, had been diagnosed and treated for breast cancer. Twelve years later, she began having hip and lower back pain and was diagnosed with bony metastatic spread. She was started on hormone-suppressing therapy as well as daily ibandronic acid. Four years later, she began having new lower limb and groin pain. Radiography, bone scans and other tests indicated further metastatic spread to her left femur.

While she was waiting for scheduled radiotherapy, she fell, fracturing her left femur. Radiographs revealed AFF, presumed secondary to her BP therapy rather than metastasis. She underwent intramedullary nail fixation.

Evidence suggests that AFFs are stress fractures, the clinicians say. Repetitive loading on bone can lead to micro cracks, which are even more vulnerable to stress when BPs suppress the normal bone repair process.

Atypical femoral fracture is rare. Most cases have been patients receiving intravenous BP; to the clinicians’ knowledge this is the first report of AFF with an oral BP prescribed for bone metastatic breast cancer. But incidence of AFF grows with prolonged treatment, and the risk is raised with oral dosing, which is much higher in cancer cases, the clinicians note, compared with osteoporosis.

Because patients often have prodromal pain before an overt break, the clinicians suggest asking all oncology patients on BP about pain in thigh, hip, or groin. Bone scans and magnetic resonance imaging may reveal an imminent fracture. The clinicians caution that AFFs can be bilateral, so the opposite side also should be imaged.

Source:

Espey R, Grimes S, Heyburn G, Kealey WD. BMJ Case Rep. 2017;2017. pii: bcr-2016-217489.
doi: 10.1136/bcr-2016-217489.

As more people are surviving breast cancer, more will be given bisphosphonate (BP) for bone metastases—and may be at risk for treatment adverse effects, such as atypical femoral fracture (AFF). Clinicians from Royal Victoria Hospital, Belfast, United Kingdom, describe what they learned in the first reported case of AFF caused by daily ibandronate.

The patient, a 55-year-old woman, had been diagnosed and treated for breast cancer. Twelve years later, she began having hip and lower back pain and was diagnosed with bony metastatic spread. She was started on hormone-suppressing therapy as well as daily ibandronic acid. Four years later, she began having new lower limb and groin pain. Radiography, bone scans and other tests indicated further metastatic spread to her left femur.

While she was waiting for scheduled radiotherapy, she fell, fracturing her left femur. Radiographs revealed AFF, presumed secondary to her BP therapy rather than metastasis. She underwent intramedullary nail fixation.

Evidence suggests that AFFs are stress fractures, the clinicians say. Repetitive loading on bone can lead to micro cracks, which are even more vulnerable to stress when BPs suppress the normal bone repair process.

Atypical femoral fracture is rare. Most cases have been patients receiving intravenous BP; to the clinicians’ knowledge this is the first report of AFF with an oral BP prescribed for bone metastatic breast cancer. But incidence of AFF grows with prolonged treatment, and the risk is raised with oral dosing, which is much higher in cancer cases, the clinicians note, compared with osteoporosis.

Because patients often have prodromal pain before an overt break, the clinicians suggest asking all oncology patients on BP about pain in thigh, hip, or groin. Bone scans and magnetic resonance imaging may reveal an imminent fracture. The clinicians caution that AFFs can be bilateral, so the opposite side also should be imaged.

Source:

Espey R, Grimes S, Heyburn G, Kealey WD. BMJ Case Rep. 2017;2017. pii: bcr-2016-217489.
doi: 10.1136/bcr-2016-217489.

As more people are surviving breast cancer, more will be given bisphosphonate (BP) for bone metastases—and may be at risk for treatment adverse effects, such as atypical femoral fracture (AFF). Clinicians from Royal Victoria Hospital, Belfast, United Kingdom, describe what they learned in the first reported case of AFF caused by daily ibandronate.

The patient, a 55-year-old woman, had been diagnosed and treated for breast cancer. Twelve years later, she began having hip and lower back pain and was diagnosed with bony metastatic spread. She was started on hormone-suppressing therapy as well as daily ibandronic acid. Four years later, she began having new lower limb and groin pain. Radiography, bone scans and other tests indicated further metastatic spread to her left femur.

While she was waiting for scheduled radiotherapy, she fell, fracturing her left femur. Radiographs revealed AFF, presumed secondary to her BP therapy rather than metastasis. She underwent intramedullary nail fixation.

Evidence suggests that AFFs are stress fractures, the clinicians say. Repetitive loading on bone can lead to micro cracks, which are even more vulnerable to stress when BPs suppress the normal bone repair process.

Atypical femoral fracture is rare. Most cases have been patients receiving intravenous BP; to the clinicians’ knowledge this is the first report of AFF with an oral BP prescribed for bone metastatic breast cancer. But incidence of AFF grows with prolonged treatment, and the risk is raised with oral dosing, which is much higher in cancer cases, the clinicians note, compared with osteoporosis.

Because patients often have prodromal pain before an overt break, the clinicians suggest asking all oncology patients on BP about pain in thigh, hip, or groin. Bone scans and magnetic resonance imaging may reveal an imminent fracture. The clinicians caution that AFFs can be bilateral, so the opposite side also should be imaged.

Source:

Espey R, Grimes S, Heyburn G, Kealey WD. BMJ Case Rep. 2017;2017. pii: bcr-2016-217489.
doi: 10.1136/bcr-2016-217489.

In an “important first,” the FDA has fast-tracked a cancer treatment based on a biomarker rather than on the location of the tumor.

Pembrolizumab (Keytruda) has already been approved for certain patients with metastatic melanoma, metastatic non-small cell lung cancer, and other cancers. With the new approval, pembrolizumab is now indicated for adult and pediatric patients with unresectable or metastatic solid tumors that have a biomarker known as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Microsatellite instability-high and dMMR tumors have abnormalities that affect the proper repair of DNA inside the cell. Pembrolizumab blocks a cellular pathway (PD-1/PD-L1—proteins found in immune cells and some cancer cells), which may help the immune system fight the cancer cells.

Tumors with the biomarkers are most commonly found in colorectal, endometrial, and gastrointestinal cancers. About 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors. Less commonly, they are found in cancers in the breast, prostate, bladder, thyroid gland, and other locations.

In 5 clinical trials, of 149 patients treated with pembrolizumab for 15 cancer types, 40% had a complete or partial response. For most of those patients, the response lasted ≥ 6 months.

In an “important first,” the FDA has fast-tracked a cancer treatment based on a biomarker rather than on the location of the tumor.

Pembrolizumab (Keytruda) has already been approved for certain patients with metastatic melanoma, metastatic non-small cell lung cancer, and other cancers. With the new approval, pembrolizumab is now indicated for adult and pediatric patients with unresectable or metastatic solid tumors that have a biomarker known as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Microsatellite instability-high and dMMR tumors have abnormalities that affect the proper repair of DNA inside the cell. Pembrolizumab blocks a cellular pathway (PD-1/PD-L1—proteins found in immune cells and some cancer cells), which may help the immune system fight the cancer cells.

Tumors with the biomarkers are most commonly found in colorectal, endometrial, and gastrointestinal cancers. About 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors. Less commonly, they are found in cancers in the breast, prostate, bladder, thyroid gland, and other locations.

In 5 clinical trials, of 149 patients treated with pembrolizumab for 15 cancer types, 40% had a complete or partial response. For most of those patients, the response lasted ≥ 6 months.

In an “important first,” the FDA has fast-tracked a cancer treatment based on a biomarker rather than on the location of the tumor.

Pembrolizumab (Keytruda) has already been approved for certain patients with metastatic melanoma, metastatic non-small cell lung cancer, and other cancers. With the new approval, pembrolizumab is now indicated for adult and pediatric patients with unresectable or metastatic solid tumors that have a biomarker known as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Microsatellite instability-high and dMMR tumors have abnormalities that affect the proper repair of DNA inside the cell. Pembrolizumab blocks a cellular pathway (PD-1/PD-L1—proteins found in immune cells and some cancer cells), which may help the immune system fight the cancer cells.

Tumors with the biomarkers are most commonly found in colorectal, endometrial, and gastrointestinal cancers. About 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors. Less commonly, they are found in cancers in the breast, prostate, bladder, thyroid gland, and other locations.

In 5 clinical trials, of 149 patients treated with pembrolizumab for 15 cancer types, 40% had a complete or partial response. For most of those patients, the response lasted ≥ 6 months.

Living in a racially segregated neighborhood can be bad for the blood pressure (BP) if you are a black adult, according to Northwestern University researchers. They found that simply moving away from that neighborhood is enough to reduce systolic blood pressure 1 to 5 points.

In the study, which was partly funded by the NIH, the researchers examined BP readings for 2,280 black adults who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The participants were initially screened in 1985 and 1986 then reexamined several times over the next 25 years. The Northwestern study is the first to look at the longitudinal effects of segregation on BP compare the effect within the same individuals. Previous research had looked at single points in time.

The researchers categorized neighborhood segregation as high, medium, or low, using a scale that compareed the percentage of black residents in a neighborhood to the surrounding area. When neighborhoods were more segregated, the participants had small but statistically significant increases in systolic BP. Less segregation equaled a “notable” drop in BP.

Participants who lived in a highly segregated neighborhood and moved to a less segregated one saw the most significant improvements. Those who moved temporarily saw a 1 mm Hg drop. A permanent move equaled 3 to 5 mm Hg. That’s a “powerful effect,” said lead author Kiarri Kershaw, assistant professor of preventive medicine at Northwestern. Just 1 mm Hg lower at the population level, she notes, could mean “meaningful” reductions in heart attacks, strokes, and heart failure. The associations persisted even after the researchers accounted for marital status, body mass index, smoking history, physical activity, and socioeconomic status of the community.

The changes in blood pressure were not related to poverty or household income. Kershaw says less stress, achieved by reducing exposure to violence and improving opportunities for socioeconomic mobility, is “likely a key factor.” Other factors that could help include improving access to health-promoting resources, such as full-service grocery stores, recreation centers, and health care clinics.

Living in a racially segregated neighborhood can be bad for the blood pressure (BP) if you are a black adult, according to Northwestern University researchers. They found that simply moving away from that neighborhood is enough to reduce systolic blood pressure 1 to 5 points.

In the study, which was partly funded by the NIH, the researchers examined BP readings for 2,280 black adults who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The participants were initially screened in 1985 and 1986 then reexamined several times over the next 25 years. The Northwestern study is the first to look at the longitudinal effects of segregation on BP compare the effect within the same individuals. Previous research had looked at single points in time.

The researchers categorized neighborhood segregation as high, medium, or low, using a scale that compareed the percentage of black residents in a neighborhood to the surrounding area. When neighborhoods were more segregated, the participants had small but statistically significant increases in systolic BP. Less segregation equaled a “notable” drop in BP.

Participants who lived in a highly segregated neighborhood and moved to a less segregated one saw the most significant improvements. Those who moved temporarily saw a 1 mm Hg drop. A permanent move equaled 3 to 5 mm Hg. That’s a “powerful effect,” said lead author Kiarri Kershaw, assistant professor of preventive medicine at Northwestern. Just 1 mm Hg lower at the population level, she notes, could mean “meaningful” reductions in heart attacks, strokes, and heart failure. The associations persisted even after the researchers accounted for marital status, body mass index, smoking history, physical activity, and socioeconomic status of the community.

The changes in blood pressure were not related to poverty or household income. Kershaw says less stress, achieved by reducing exposure to violence and improving opportunities for socioeconomic mobility, is “likely a key factor.” Other factors that could help include improving access to health-promoting resources, such as full-service grocery stores, recreation centers, and health care clinics.

Living in a racially segregated neighborhood can be bad for the blood pressure (BP) if you are a black adult, according to Northwestern University researchers. They found that simply moving away from that neighborhood is enough to reduce systolic blood pressure 1 to 5 points.

In the study, which was partly funded by the NIH, the researchers examined BP readings for 2,280 black adults who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The participants were initially screened in 1985 and 1986 then reexamined several times over the next 25 years. The Northwestern study is the first to look at the longitudinal effects of segregation on BP compare the effect within the same individuals. Previous research had looked at single points in time.

The researchers categorized neighborhood segregation as high, medium, or low, using a scale that compareed the percentage of black residents in a neighborhood to the surrounding area. When neighborhoods were more segregated, the participants had small but statistically significant increases in systolic BP. Less segregation equaled a “notable” drop in BP.

Participants who lived in a highly segregated neighborhood and moved to a less segregated one saw the most significant improvements. Those who moved temporarily saw a 1 mm Hg drop. A permanent move equaled 3 to 5 mm Hg. That’s a “powerful effect,” said lead author Kiarri Kershaw, assistant professor of preventive medicine at Northwestern. Just 1 mm Hg lower at the population level, she notes, could mean “meaningful” reductions in heart attacks, strokes, and heart failure. The associations persisted even after the researchers accounted for marital status, body mass index, smoking history, physical activity, and socioeconomic status of the community.

The changes in blood pressure were not related to poverty or household income. Kershaw says less stress, achieved by reducing exposure to violence and improving opportunities for socioeconomic mobility, is “likely a key factor.” Other factors that could help include improving access to health-promoting resources, such as full-service grocery stores, recreation centers, and health care clinics.

Between 2009 and 2014, hepatitis C virus (HCV) infection among women giving birth rose 89%, from 1.8 to 3.4 per live births, according to a study published in Morbidity and Mortality Weekly Report. The researchers say, geographically, the increase in maternal HCV infection mirrors increases in HCV incidence among adults. The highest infection rate was in West Virginia, which had 22.6 per 1,000 live births. Next was Tennessee with 10.1. State infection rates varied widely: Hawaii had the lowest rate, of 0.7.

In Tennessee, the prevalence of maternal HCV infection increased 163%, from 3.8 per 1,000 in 2009 to 10 in 2014. But even among the 95 Tennessee counties, rates varied substantially. The highest rates were in the 52 Appalachian counties. Campbell County had 78 per 1,000 births. Compared with women in urban areas, pregnant women from rural areas had triple the odds of HCV infection. The rise in infection among pregnant women coincides with the rises in heroin and prescription opioid epidemics, which also disproportionately affect rural populations.

Analyzing the Tennessee births, researchers found that the odds of HCV infection were about 5 times higher among women who smoked cigarettes during pregnancy. Concurrent infections were another serious risk factor, with hepatitis B virus infection boosting the odds of HCV infection by nearly 17 times.

HCV infection is a growing—but modifiable—threat among pregnant women, the researchers say. The rise in infection is “particularly concerning,” in light of recent research that has found poor follow-up of HCV-exposed infants. The researchers cite a Philadelphia study that found only 16% of HCV-exposed infants were appropriately followed. That could mean that infected infants are going undetected, the researchers say. The rate of transmission from mothers to infants is estimated at 6%; it’s important for exposed infants to be followed for evidence of seroconversion. But anti-HCV antibody tests can’t be completed until 18 months because passively acquired maternal antibodies can persist. Testing for HCV ribonucleic acid can be performed earlier.

The CDC and the American College of Obstetricians and Gynecologists recommend selective screening of pregnant women at high risk for HCV infection, particularly those with a history of injection drug use or long-term hemodialysis.

Between 2009 and 2014, hepatitis C virus (HCV) infection among women giving birth rose 89%, from 1.8 to 3.4 per live births, according to a study published in Morbidity and Mortality Weekly Report. The researchers say, geographically, the increase in maternal HCV infection mirrors increases in HCV incidence among adults. The highest infection rate was in West Virginia, which had 22.6 per 1,000 live births. Next was Tennessee with 10.1. State infection rates varied widely: Hawaii had the lowest rate, of 0.7.

In Tennessee, the prevalence of maternal HCV infection increased 163%, from 3.8 per 1,000 in 2009 to 10 in 2014. But even among the 95 Tennessee counties, rates varied substantially. The highest rates were in the 52 Appalachian counties. Campbell County had 78 per 1,000 births. Compared with women in urban areas, pregnant women from rural areas had triple the odds of HCV infection. The rise in infection among pregnant women coincides with the rises in heroin and prescription opioid epidemics, which also disproportionately affect rural populations.

Analyzing the Tennessee births, researchers found that the odds of HCV infection were about 5 times higher among women who smoked cigarettes during pregnancy. Concurrent infections were another serious risk factor, with hepatitis B virus infection boosting the odds of HCV infection by nearly 17 times.

HCV infection is a growing—but modifiable—threat among pregnant women, the researchers say. The rise in infection is “particularly concerning,” in light of recent research that has found poor follow-up of HCV-exposed infants. The researchers cite a Philadelphia study that found only 16% of HCV-exposed infants were appropriately followed. That could mean that infected infants are going undetected, the researchers say. The rate of transmission from mothers to infants is estimated at 6%; it’s important for exposed infants to be followed for evidence of seroconversion. But anti-HCV antibody tests can’t be completed until 18 months because passively acquired maternal antibodies can persist. Testing for HCV ribonucleic acid can be performed earlier.

The CDC and the American College of Obstetricians and Gynecologists recommend selective screening of pregnant women at high risk for HCV infection, particularly those with a history of injection drug use or long-term hemodialysis.

Between 2009 and 2014, hepatitis C virus (HCV) infection among women giving birth rose 89%, from 1.8 to 3.4 per live births, according to a study published in Morbidity and Mortality Weekly Report. The researchers say, geographically, the increase in maternal HCV infection mirrors increases in HCV incidence among adults. The highest infection rate was in West Virginia, which had 22.6 per 1,000 live births. Next was Tennessee with 10.1. State infection rates varied widely: Hawaii had the lowest rate, of 0.7.

In Tennessee, the prevalence of maternal HCV infection increased 163%, from 3.8 per 1,000 in 2009 to 10 in 2014. But even among the 95 Tennessee counties, rates varied substantially. The highest rates were in the 52 Appalachian counties. Campbell County had 78 per 1,000 births. Compared with women in urban areas, pregnant women from rural areas had triple the odds of HCV infection. The rise in infection among pregnant women coincides with the rises in heroin and prescription opioid epidemics, which also disproportionately affect rural populations.

Analyzing the Tennessee births, researchers found that the odds of HCV infection were about 5 times higher among women who smoked cigarettes during pregnancy. Concurrent infections were another serious risk factor, with hepatitis B virus infection boosting the odds of HCV infection by nearly 17 times.

HCV infection is a growing—but modifiable—threat among pregnant women, the researchers say. The rise in infection is “particularly concerning,” in light of recent research that has found poor follow-up of HCV-exposed infants. The researchers cite a Philadelphia study that found only 16% of HCV-exposed infants were appropriately followed. That could mean that infected infants are going undetected, the researchers say. The rate of transmission from mothers to infants is estimated at 6%; it’s important for exposed infants to be followed for evidence of seroconversion. But anti-HCV antibody tests can’t be completed until 18 months because passively acquired maternal antibodies can persist. Testing for HCV ribonucleic acid can be performed earlier.

The CDC and the American College of Obstetricians and Gynecologists recommend selective screening of pregnant women at high risk for HCV infection, particularly those with a history of injection drug use or long-term hemodialysis.

Take a brand-new research facility, then add a neighboring U.S. Army base with one of the largest veteran populations of any health care network and a world-class team of researchers—that’s a “recipe for success,” says Dr. Michael Russell, director of the VA Center of Excellence for Research on Returning War Veterans in Waco, Texas.

The 53,000-square-foot center is designed to conduct state-of-the-art research on mental health problems associated with PTSD and TBI, “signature wounds” of conflicts in Afghanistan and the Middle East. The flagship study is named Project MAVEREX. Researchers will examine whether the inability of the regions in injured brains to communicate with one another worsens behavior outcomes. Using “cutting-edge data analysis techniques,” they hope to characterize the effects of TBI on brain structure and function “with very high precision,” says Dr. Evan Gordon, a cognitive neuroscientist working on MAVEREX.

The Center of Excellence is on the campus of the historic Doris Miller VAMC. The facility has space for 75 staff members and faculty as well as 25 trainees. It features multiple examination rooms, observation rooms, electrocardiography, electroencephalography, a 3 Tesla MRI, a transcranial magnetic stimulation suite, and a custom-built laboratory wing.

Take a brand-new research facility, then add a neighboring U.S. Army base with one of the largest veteran populations of any health care network and a world-class team of researchers—that’s a “recipe for success,” says Dr. Michael Russell, director of the VA Center of Excellence for Research on Returning War Veterans in Waco, Texas.

The 53,000-square-foot center is designed to conduct state-of-the-art research on mental health problems associated with PTSD and TBI, “signature wounds” of conflicts in Afghanistan and the Middle East. The flagship study is named Project MAVEREX. Researchers will examine whether the inability of the regions in injured brains to communicate with one another worsens behavior outcomes. Using “cutting-edge data analysis techniques,” they hope to characterize the effects of TBI on brain structure and function “with very high precision,” says Dr. Evan Gordon, a cognitive neuroscientist working on MAVEREX.

The Center of Excellence is on the campus of the historic Doris Miller VAMC. The facility has space for 75 staff members and faculty as well as 25 trainees. It features multiple examination rooms, observation rooms, electrocardiography, electroencephalography, a 3 Tesla MRI, a transcranial magnetic stimulation suite, and a custom-built laboratory wing.

Take a brand-new research facility, then add a neighboring U.S. Army base with one of the largest veteran populations of any health care network and a world-class team of researchers—that’s a “recipe for success,” says Dr. Michael Russell, director of the VA Center of Excellence for Research on Returning War Veterans in Waco, Texas.

The 53,000-square-foot center is designed to conduct state-of-the-art research on mental health problems associated with PTSD and TBI, “signature wounds” of conflicts in Afghanistan and the Middle East. The flagship study is named Project MAVEREX. Researchers will examine whether the inability of the regions in injured brains to communicate with one another worsens behavior outcomes. Using “cutting-edge data analysis techniques,” they hope to characterize the effects of TBI on brain structure and function “with very high precision,” says Dr. Evan Gordon, a cognitive neuroscientist working on MAVEREX.

The Center of Excellence is on the campus of the historic Doris Miller VAMC. The facility has space for 75 staff members and faculty as well as 25 trainees. It features multiple examination rooms, observation rooms, electrocardiography, electroencephalography, a 3 Tesla MRI, a transcranial magnetic stimulation suite, and a custom-built laboratory wing.

The Million Veteran Program (MVP) is now the largest genomic database in the world, with more than 550,000 veterans enrolled. Researchers have been mining the data for a variety of studies, including studies to examine the genetic risk factors for chronic use of alcohol, tobacco, and opioids.

Most people who smoke or use drugs also drink alcohol, and changes in one behavior are likely to be associated with changes in the others, according to researchers from the  VA Connecticut Healthcare System and the Corporal Michael J. Crescenz VAMC. That likelihood suggests a shared genetic risk for multiple-substance use, but to date, studies on the subject have been limited by the small size of the available samples, the researchers say. The MVP is providing a unique opportunity to analyze massive amounts of longitudinal data to discover potential genetic links.

The answers also may provide opportunities for treatment and prevention. For example, it may be possible to reduce the use of multiple harmful substances simultaneously with more than 1 medication.

The first target in this “ambitious effort,” the researchers say, is heavy drinking. They’re using data from the Veterans Aging Cohort Study and from the AUDIT-C, a self-report questionnaire given annually to veterans, which quantifies recent drinking. The researchers plan to validate their initial findings, already published, and then combine that information with the genotype information from the MVP to identify novel genetic predictors of heavy drinking.

The researchers have begun to use a similar approach to study chronic opioid use and smoking. Ultimately, they plan to integrate all the findings to yield genetic profiles for multisubstance use.

The Million Veteran Program (MVP) is now the largest genomic database in the world, with more than 550,000 veterans enrolled. Researchers have been mining the data for a variety of studies, including studies to examine the genetic risk factors for chronic use of alcohol, tobacco, and opioids.

Most people who smoke or use drugs also drink alcohol, and changes in one behavior are likely to be associated with changes in the others, according to researchers from the  VA Connecticut Healthcare System and the Corporal Michael J. Crescenz VAMC. That likelihood suggests a shared genetic risk for multiple-substance use, but to date, studies on the subject have been limited by the small size of the available samples, the researchers say. The MVP is providing a unique opportunity to analyze massive amounts of longitudinal data to discover potential genetic links.

The answers also may provide opportunities for treatment and prevention. For example, it may be possible to reduce the use of multiple harmful substances simultaneously with more than 1 medication.

The first target in this “ambitious effort,” the researchers say, is heavy drinking. They’re using data from the Veterans Aging Cohort Study and from the AUDIT-C, a self-report questionnaire given annually to veterans, which quantifies recent drinking. The researchers plan to validate their initial findings, already published, and then combine that information with the genotype information from the MVP to identify novel genetic predictors of heavy drinking.

The researchers have begun to use a similar approach to study chronic opioid use and smoking. Ultimately, they plan to integrate all the findings to yield genetic profiles for multisubstance use.

The Million Veteran Program (MVP) is now the largest genomic database in the world, with more than 550,000 veterans enrolled. Researchers have been mining the data for a variety of studies, including studies to examine the genetic risk factors for chronic use of alcohol, tobacco, and opioids.

Most people who smoke or use drugs also drink alcohol, and changes in one behavior are likely to be associated with changes in the others, according to researchers from the  VA Connecticut Healthcare System and the Corporal Michael J. Crescenz VAMC. That likelihood suggests a shared genetic risk for multiple-substance use, but to date, studies on the subject have been limited by the small size of the available samples, the researchers say. The MVP is providing a unique opportunity to analyze massive amounts of longitudinal data to discover potential genetic links.

The answers also may provide opportunities for treatment and prevention. For example, it may be possible to reduce the use of multiple harmful substances simultaneously with more than 1 medication.

The first target in this “ambitious effort,” the researchers say, is heavy drinking. They’re using data from the Veterans Aging Cohort Study and from the AUDIT-C, a self-report questionnaire given annually to veterans, which quantifies recent drinking. The researchers plan to validate their initial findings, already published, and then combine that information with the genotype information from the MVP to identify novel genetic predictors of heavy drinking.

The researchers have begun to use a similar approach to study chronic opioid use and smoking. Ultimately, they plan to integrate all the findings to yield genetic profiles for multisubstance use.

Pregnancy is generally found to offer a respite from multiple sclerosis (MS). Pregnant women rarely develop MS or to have relapses. But in a unique and challenging case, a woman in her 14th week of her second pregnancy developed signs and symptoms of tumefactive multiple sclerosis (TMS), a rare subtype of MS. The TMS was only one of several unexpected clinical puzzles, according to the clinicians reporting on the case.

The patient, who had been healthy, was admitted with acute onset of paresthesias and word-finding difficulty. She had just had a long drive from Florida, and the the clinicians first assumed that she was fatigued from the trip and from the pregnancy. A magnetic resonance imaging (MRI) scan of the brain, however, suggested an ischemic event.

While hospitalized, the patient’s condition rapidly worsened. More scan and test findings proved consistent with TMS. A repeat MRI scan showed interval progression with a growing tumefactive demyelinating lesion (TDL) with diffuse surrounding edema and new periventricular signal changes. Although rare, TDLs often represent fulminant forms of MS, the clinicians note. Because the lesions mimic strokes, tumors, and abscesses, diagnosis is difficult. Moreover, the gadolinium (which was avoided because it can cause birth defects) might have helped them visualize lesions sooner.

The patient was started on high-dose IV methylprednisolone and plasma exchange, but the response was mild. The poor response to both treatment modalities is infrequent in TMS, the clinicians say—yet another unforeseen obstacle.

In addition to counseling the patient about the usual protective effects of pregnancy, her clinicians counseled her “extensively” about natalizumab and the possible beneficial effects of disease-modifying therapies. But the patient made the difficult decision to terminate the pregnancy, in part because she felt it was better to focus on her existing child rather than on caring for 2 young children while having a chronic progressive disease with uncertain recovery.

Another surprise was in store. Within 12 hours after an uncomplicated dilatation and curettage, the patient was able to move her right arm. That “drastic improvement” was followed by moderate improvement in her right leg. Her “paradoxical” improvement after the termination might indicate a “different from expected” hormonal influence in the pathogenesis of TMS, the clinicians say, but more likely represents a delayed corroborating effect of steroids and plasma exchange.

In the following weeks, the patient’s recovery was “satisfying” with gradual improvement and partial return of expressive language.  Eighteen months later, the patient was clinically stable on natalizumab.

Source:
Pakneshan S, Bernitsas E. BMJ Case Rep. 2017. pii: bcr-2017-219534.
 doi: 10.1136/bcr-2017-219534.

Pregnancy is generally found to offer a respite from multiple sclerosis (MS). Pregnant women rarely develop MS or to have relapses. But in a unique and challenging case, a woman in her 14th week of her second pregnancy developed signs and symptoms of tumefactive multiple sclerosis (TMS), a rare subtype of MS. The TMS was only one of several unexpected clinical puzzles, according to the clinicians reporting on the case.

The patient, who had been healthy, was admitted with acute onset of paresthesias and word-finding difficulty. She had just had a long drive from Florida, and the the clinicians first assumed that she was fatigued from the trip and from the pregnancy. A magnetic resonance imaging (MRI) scan of the brain, however, suggested an ischemic event.

While hospitalized, the patient’s condition rapidly worsened. More scan and test findings proved consistent with TMS. A repeat MRI scan showed interval progression with a growing tumefactive demyelinating lesion (TDL) with diffuse surrounding edema and new periventricular signal changes. Although rare, TDLs often represent fulminant forms of MS, the clinicians note. Because the lesions mimic strokes, tumors, and abscesses, diagnosis is difficult. Moreover, the gadolinium (which was avoided because it can cause birth defects) might have helped them visualize lesions sooner.

The patient was started on high-dose IV methylprednisolone and plasma exchange, but the response was mild. The poor response to both treatment modalities is infrequent in TMS, the clinicians say—yet another unforeseen obstacle.

In addition to counseling the patient about the usual protective effects of pregnancy, her clinicians counseled her “extensively” about natalizumab and the possible beneficial effects of disease-modifying therapies. But the patient made the difficult decision to terminate the pregnancy, in part because she felt it was better to focus on her existing child rather than on caring for 2 young children while having a chronic progressive disease with uncertain recovery.

Another surprise was in store. Within 12 hours after an uncomplicated dilatation and curettage, the patient was able to move her right arm. That “drastic improvement” was followed by moderate improvement in her right leg. Her “paradoxical” improvement after the termination might indicate a “different from expected” hormonal influence in the pathogenesis of TMS, the clinicians say, but more likely represents a delayed corroborating effect of steroids and plasma exchange.

In the following weeks, the patient’s recovery was “satisfying” with gradual improvement and partial return of expressive language.  Eighteen months later, the patient was clinically stable on natalizumab.

Source:
Pakneshan S, Bernitsas E. BMJ Case Rep. 2017. pii: bcr-2017-219534.
 doi: 10.1136/bcr-2017-219534.

Pregnancy is generally found to offer a respite from multiple sclerosis (MS). Pregnant women rarely develop MS or to have relapses. But in a unique and challenging case, a woman in her 14th week of her second pregnancy developed signs and symptoms of tumefactive multiple sclerosis (TMS), a rare subtype of MS. The TMS was only one of several unexpected clinical puzzles, according to the clinicians reporting on the case.

The patient, who had been healthy, was admitted with acute onset of paresthesias and word-finding difficulty. She had just had a long drive from Florida, and the the clinicians first assumed that she was fatigued from the trip and from the pregnancy. A magnetic resonance imaging (MRI) scan of the brain, however, suggested an ischemic event.

While hospitalized, the patient’s condition rapidly worsened. More scan and test findings proved consistent with TMS. A repeat MRI scan showed interval progression with a growing tumefactive demyelinating lesion (TDL) with diffuse surrounding edema and new periventricular signal changes. Although rare, TDLs often represent fulminant forms of MS, the clinicians note. Because the lesions mimic strokes, tumors, and abscesses, diagnosis is difficult. Moreover, the gadolinium (which was avoided because it can cause birth defects) might have helped them visualize lesions sooner.

The patient was started on high-dose IV methylprednisolone and plasma exchange, but the response was mild. The poor response to both treatment modalities is infrequent in TMS, the clinicians say—yet another unforeseen obstacle.

In addition to counseling the patient about the usual protective effects of pregnancy, her clinicians counseled her “extensively” about natalizumab and the possible beneficial effects of disease-modifying therapies. But the patient made the difficult decision to terminate the pregnancy, in part because she felt it was better to focus on her existing child rather than on caring for 2 young children while having a chronic progressive disease with uncertain recovery.

Another surprise was in store. Within 12 hours after an uncomplicated dilatation and curettage, the patient was able to move her right arm. That “drastic improvement” was followed by moderate improvement in her right leg. Her “paradoxical” improvement after the termination might indicate a “different from expected” hormonal influence in the pathogenesis of TMS, the clinicians say, but more likely represents a delayed corroborating effect of steroids and plasma exchange.

In the following weeks, the patient’s recovery was “satisfying” with gradual improvement and partial return of expressive language.  Eighteen months later, the patient was clinically stable on natalizumab.

Source:
Pakneshan S, Bernitsas E. BMJ Case Rep. 2017. pii: bcr-2017-219534.
 doi: 10.1136/bcr-2017-219534.