Hatanaka and colleagues investigated whether the etiology of the underlying liver disease affected the efficacy of atezolizumab and bevacizumab (A/B). They reported the results of a retrospective cohort study of 323 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A cirrhosis who started A/B between September 2020 and December 2021. Patients with viral infection were defined as those who were either serum anti–hepatitis C antibody (anti-HCV Ab)- or hepatitis B surface antigen (HBs-Ag)-positive, while patients with nonviral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. After propensity matching, no significant difference in response rate ([RR] 20.6% vs 24.6% in viral and nonviral patients), disease control rate (68.3% vs 69.0%), progression-free survival ([PFS] 7.0 months vs 6.2 months), or 12-month overall survival ([OS] 65.5% vs 71.7%) was seen. The authors concluded that the underlying etiology of liver disease in patients with HCC does not affect the response to treatment with A/B.

Scheiner and colleagues evaluated the efficacy of immunotherapy in patients with HCC who had already received immune checkpoint inhibitors (ICI) in a previous line of therapy. The authors reported the results of an international, retrospective multicenter study of 58 patients with HCC who received at least two lines of ICI-based therapies. The first ICI was discontinued due to disease progression in 90%. Nonetheless, the RR to the second ICI was 26% (compared with 22% for the first ICI), with a time-to-progression (TTP) of 5.4 months (95% CI, 3.0-7.7) for the first ICI and 5.2 months (95% CI, 3.3-7.0) for the second ICI. Grade 3/4 treatment-related adverse events were observed in 16% and 17% of patients with the first and second ICI, respectively. Therefore, the authors believe that ICI rechallenge is safe and results in a treatment benefit for a similar proportion of HCC patients, as is seen with the first ICI treatment. They suggest that ICI-based regimens should be studied in prospective trials of patients who progressed on first-line immunotherapy.

Finally, Kim and colleagues reported outcomes of patients who developed anti-drug antibodies (ADA) against atezolizumab while on A/B. In this prospective cohort study, 174 patients with advanced HCC who were treated with first-line A/B were tested for serum ADA levels prior to treatment and at 3 weeks (cycle 2 day 1 [C2D1]). Clinically, patients with progressive disease exhibited higher ADA levels (median 65.2 [0-520.4] ng/mL) at C2D1 than responders (0-117.5 ng/mL). Patients with high ADA levels at C2D1 had a reduced response rate (29%-34% vs 7-11%) and worse PFS and OS. The investigators found that very high ADA levels (≥ 1000 ng/mL) at 3 weeks were consistently associated with poor clinical outcomes due to reduced systemic exposure to atezolizumab and impaired proliferation and activation of peripheral CD8-positive T cells. They suggested future validation and standardization of ADA assays to optimize treatment with atezolizumab in patients with uHCC.

Hatanaka and colleagues investigated whether the etiology of the underlying liver disease affected the efficacy of atezolizumab and bevacizumab (A/B). They reported the results of a retrospective cohort study of 323 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A cirrhosis who started A/B between September 2020 and December 2021. Patients with viral infection were defined as those who were either serum anti–hepatitis C antibody (anti-HCV Ab)- or hepatitis B surface antigen (HBs-Ag)-positive, while patients with nonviral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. After propensity matching, no significant difference in response rate ([RR] 20.6% vs 24.6% in viral and nonviral patients), disease control rate (68.3% vs 69.0%), progression-free survival ([PFS] 7.0 months vs 6.2 months), or 12-month overall survival ([OS] 65.5% vs 71.7%) was seen. The authors concluded that the underlying etiology of liver disease in patients with HCC does not affect the response to treatment with A/B.

Scheiner and colleagues evaluated the efficacy of immunotherapy in patients with HCC who had already received immune checkpoint inhibitors (ICI) in a previous line of therapy. The authors reported the results of an international, retrospective multicenter study of 58 patients with HCC who received at least two lines of ICI-based therapies. The first ICI was discontinued due to disease progression in 90%. Nonetheless, the RR to the second ICI was 26% (compared with 22% for the first ICI), with a time-to-progression (TTP) of 5.4 months (95% CI, 3.0-7.7) for the first ICI and 5.2 months (95% CI, 3.3-7.0) for the second ICI. Grade 3/4 treatment-related adverse events were observed in 16% and 17% of patients with the first and second ICI, respectively. Therefore, the authors believe that ICI rechallenge is safe and results in a treatment benefit for a similar proportion of HCC patients, as is seen with the first ICI treatment. They suggest that ICI-based regimens should be studied in prospective trials of patients who progressed on first-line immunotherapy.

Finally, Kim and colleagues reported outcomes of patients who developed anti-drug antibodies (ADA) against atezolizumab while on A/B. In this prospective cohort study, 174 patients with advanced HCC who were treated with first-line A/B were tested for serum ADA levels prior to treatment and at 3 weeks (cycle 2 day 1 [C2D1]). Clinically, patients with progressive disease exhibited higher ADA levels (median 65.2 [0-520.4] ng/mL) at C2D1 than responders (0-117.5 ng/mL). Patients with high ADA levels at C2D1 had a reduced response rate (29%-34% vs 7-11%) and worse PFS and OS. The investigators found that very high ADA levels (≥ 1000 ng/mL) at 3 weeks were consistently associated with poor clinical outcomes due to reduced systemic exposure to atezolizumab and impaired proliferation and activation of peripheral CD8-positive T cells. They suggested future validation and standardization of ADA assays to optimize treatment with atezolizumab in patients with uHCC.

Hatanaka and colleagues investigated whether the etiology of the underlying liver disease affected the efficacy of atezolizumab and bevacizumab (A/B). They reported the results of a retrospective cohort study of 323 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A cirrhosis who started A/B between September 2020 and December 2021. Patients with viral infection were defined as those who were either serum anti–hepatitis C antibody (anti-HCV Ab)- or hepatitis B surface antigen (HBs-Ag)-positive, while patients with nonviral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. After propensity matching, no significant difference in response rate ([RR] 20.6% vs 24.6% in viral and nonviral patients), disease control rate (68.3% vs 69.0%), progression-free survival ([PFS] 7.0 months vs 6.2 months), or 12-month overall survival ([OS] 65.5% vs 71.7%) was seen. The authors concluded that the underlying etiology of liver disease in patients with HCC does not affect the response to treatment with A/B.

Scheiner and colleagues evaluated the efficacy of immunotherapy in patients with HCC who had already received immune checkpoint inhibitors (ICI) in a previous line of therapy. The authors reported the results of an international, retrospective multicenter study of 58 patients with HCC who received at least two lines of ICI-based therapies. The first ICI was discontinued due to disease progression in 90%. Nonetheless, the RR to the second ICI was 26% (compared with 22% for the first ICI), with a time-to-progression (TTP) of 5.4 months (95% CI, 3.0-7.7) for the first ICI and 5.2 months (95% CI, 3.3-7.0) for the second ICI. Grade 3/4 treatment-related adverse events were observed in 16% and 17% of patients with the first and second ICI, respectively. Therefore, the authors believe that ICI rechallenge is safe and results in a treatment benefit for a similar proportion of HCC patients, as is seen with the first ICI treatment. They suggest that ICI-based regimens should be studied in prospective trials of patients who progressed on first-line immunotherapy.

Finally, Kim and colleagues reported outcomes of patients who developed anti-drug antibodies (ADA) against atezolizumab while on A/B. In this prospective cohort study, 174 patients with advanced HCC who were treated with first-line A/B were tested for serum ADA levels prior to treatment and at 3 weeks (cycle 2 day 1 [C2D1]). Clinically, patients with progressive disease exhibited higher ADA levels (median 65.2 [0-520.4] ng/mL) at C2D1 than responders (0-117.5 ng/mL). Patients with high ADA levels at C2D1 had a reduced response rate (29%-34% vs 7-11%) and worse PFS and OS. The investigators found that very high ADA levels (≥ 1000 ng/mL) at 3 weeks were consistently associated with poor clinical outcomes due to reduced systemic exposure to atezolizumab and impaired proliferation and activation of peripheral CD8-positive T cells. They suggested future validation and standardization of ADA assays to optimize treatment with atezolizumab in patients with uHCC.

Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.³

Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.⁴

Additional References

1. Schmid P, Cortes J, Dent R, et al; for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
2. Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
3. Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
4. Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015

Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.³

Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.⁴

Additional References

1. Schmid P, Cortes J, Dent R, et al; for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
2. Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
3. Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
4. Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015

Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.³

Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.⁴

Additional References

1. Schmid P, Cortes J, Dent R, et al; for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
2. Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
3. Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
4. Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015

CHICAGO – Taking NSAIDs for knee osteoarthritis may worsen inflammation and pain over time, suggest new data revealed at the annual meeting of the Radiological Society of North America.

Johanna Luitjens, MD, a postdoctoral scholar in the department of radiology and biomedical Imaging at the University of California, San Francisco, told this news organization that NSAIDs are frequently used to treat OA pain because inflammation is one of the main drivers of OA, but whether they actually help outcomes has been unclear. Her study suggests that they don’t help – and may actually worsen – outcomes.

Denise Fulton/MDedge News

In particular, this study looked at the impact of NSAIDs on synovitis – the inflammation of the membrane lining the knee joint – by using MRI-based structural biomarkers.

OA, the most common form of arthritis, affects more than 32 million adults in the United States and more than 500 million people worldwide.
 

No approved therapy to reduce OA progression

Little is known of the long-term effects of NSAIDs on OA progression. Currently, there’s no approved therapy to cure OA or to reduce its advance.

Dr. Luitjens noted, however, that the synovial membrane mediates development and progression of OA and may be a good therapeutic target.

Researchers studied participants from the Osteoarthritis Initiative (OAI) cohort with moderate to severe OA who used NSAIDs regularly for at least 1 year between baseline and 4-year follow-up. All participants had high-quality 3T MRI of the knee at baseline and after 4 years. Images were scored for biomarkers of inflammation, including cartilage thickness and composition.

Dr. Luitjens and associates studied 721 participants who matched the inclusion criteria (129 with and 592 participants without regular NSAID use). The available data did not further specify amounts of NSAIDs used.

At baseline, significantly higher signal intensity in the infrapatellar fat pad (IFP) was seen in patients who used NSAID, compared with controls (adjusted difference in score, 0.26; 95% confidence interval, –0.5 to –0.129; P = .039).

In addition, at the end of the study period, there was a significantly greater increase in signal intensity of IFP (adjusted difference in score, 0.46; 95% CI, 0.2-0.72; P < .001) and higher increase in effusion synovitis (adjusted difference in score, 0.27; 95% CI, 0.06-0.47;  P = .01) in NSAID users, compared with controls.

IFP size and synovial proliferation score did not different significantly between groups at the start of the study and showed no significant change over time.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared with the control group, and worsened at 4-year follow-up.

Design limits strength

Amanda E. Nelson, MD, associate professor of medicine, division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill, cautioned against assuming causality, pointing out that the OAI is an observational cohort study. (Dr. Nelson was not involved in the OAI or Dr. Luitjens’ analysis.)

“[The OAI is] large and well known, but it wasn’t designed to compare these groups, and this was a small subset,” she said in an interview. Without randomization, it’s hard to judge the results.

“It may be that people on NSAIDs for the duration of the study had more pain and had more disease to begin with, or had more symptoms or had failed other treatments,” she said, adding that the effect sizes were small.

Measures such as the IFP are ranked 0-3, so “the clinical difference of a 0.26 difference on a 0-3 scale is a bit uncertain,” she said.

Dr. Luitjens said that the researchers tried to adjust for potential confounders but agreed that randomized controlled trials are needed to better advise physicians and patients on the benefits or harms of using NSAIDs for OA.

Weighing the risks in older adults

Una Makris, MD, associate professor of internal medicine in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, noted that NSAIDs are “not always the safest option.”

“We are still in desperate need of disease-modifying drugs in OA with rigorous randomized trials to show efficacy for outcomes that are most meaningful to patients,” Dr. Makris, who was not involved in the study, told this news organization.

“OA is most common in older adults, those often with multiple comorbidities, so we must always weigh the risks – including known adverse effects which can be amplified in older adults – and benefits with the goal of improved function and less pain,” Dr. Makris said.

NSAID use also should be considered in the context of body mass index, cardiovascular risk, prior trauma or injury, other medication use, and behavioral factors, including physical activity, she said.

Dr. Luitjens, Dr. Nelson, and Dr. Makris reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHICAGO – Taking NSAIDs for knee osteoarthritis may worsen inflammation and pain over time, suggest new data revealed at the annual meeting of the Radiological Society of North America.

Johanna Luitjens, MD, a postdoctoral scholar in the department of radiology and biomedical Imaging at the University of California, San Francisco, told this news organization that NSAIDs are frequently used to treat OA pain because inflammation is one of the main drivers of OA, but whether they actually help outcomes has been unclear. Her study suggests that they don’t help – and may actually worsen – outcomes.

Denise Fulton/MDedge News

In particular, this study looked at the impact of NSAIDs on synovitis – the inflammation of the membrane lining the knee joint – by using MRI-based structural biomarkers.

OA, the most common form of arthritis, affects more than 32 million adults in the United States and more than 500 million people worldwide.
 

No approved therapy to reduce OA progression

Little is known of the long-term effects of NSAIDs on OA progression. Currently, there’s no approved therapy to cure OA or to reduce its advance.

Dr. Luitjens noted, however, that the synovial membrane mediates development and progression of OA and may be a good therapeutic target.

Researchers studied participants from the Osteoarthritis Initiative (OAI) cohort with moderate to severe OA who used NSAIDs regularly for at least 1 year between baseline and 4-year follow-up. All participants had high-quality 3T MRI of the knee at baseline and after 4 years. Images were scored for biomarkers of inflammation, including cartilage thickness and composition.

Dr. Luitjens and associates studied 721 participants who matched the inclusion criteria (129 with and 592 participants without regular NSAID use). The available data did not further specify amounts of NSAIDs used.

At baseline, significantly higher signal intensity in the infrapatellar fat pad (IFP) was seen in patients who used NSAID, compared with controls (adjusted difference in score, 0.26; 95% confidence interval, –0.5 to –0.129; P = .039).

In addition, at the end of the study period, there was a significantly greater increase in signal intensity of IFP (adjusted difference in score, 0.46; 95% CI, 0.2-0.72; P < .001) and higher increase in effusion synovitis (adjusted difference in score, 0.27; 95% CI, 0.06-0.47;  P = .01) in NSAID users, compared with controls.

IFP size and synovial proliferation score did not different significantly between groups at the start of the study and showed no significant change over time.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared with the control group, and worsened at 4-year follow-up.

Design limits strength

Amanda E. Nelson, MD, associate professor of medicine, division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill, cautioned against assuming causality, pointing out that the OAI is an observational cohort study. (Dr. Nelson was not involved in the OAI or Dr. Luitjens’ analysis.)

“[The OAI is] large and well known, but it wasn’t designed to compare these groups, and this was a small subset,” she said in an interview. Without randomization, it’s hard to judge the results.

“It may be that people on NSAIDs for the duration of the study had more pain and had more disease to begin with, or had more symptoms or had failed other treatments,” she said, adding that the effect sizes were small.

Measures such as the IFP are ranked 0-3, so “the clinical difference of a 0.26 difference on a 0-3 scale is a bit uncertain,” she said.

Dr. Luitjens said that the researchers tried to adjust for potential confounders but agreed that randomized controlled trials are needed to better advise physicians and patients on the benefits or harms of using NSAIDs for OA.

Weighing the risks in older adults

Una Makris, MD, associate professor of internal medicine in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, noted that NSAIDs are “not always the safest option.”

“We are still in desperate need of disease-modifying drugs in OA with rigorous randomized trials to show efficacy for outcomes that are most meaningful to patients,” Dr. Makris, who was not involved in the study, told this news organization.

“OA is most common in older adults, those often with multiple comorbidities, so we must always weigh the risks – including known adverse effects which can be amplified in older adults – and benefits with the goal of improved function and less pain,” Dr. Makris said.

NSAID use also should be considered in the context of body mass index, cardiovascular risk, prior trauma or injury, other medication use, and behavioral factors, including physical activity, she said.

Dr. Luitjens, Dr. Nelson, and Dr. Makris reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHICAGO – Taking NSAIDs for knee osteoarthritis may worsen inflammation and pain over time, suggest new data revealed at the annual meeting of the Radiological Society of North America.

Johanna Luitjens, MD, a postdoctoral scholar in the department of radiology and biomedical Imaging at the University of California, San Francisco, told this news organization that NSAIDs are frequently used to treat OA pain because inflammation is one of the main drivers of OA, but whether they actually help outcomes has been unclear. Her study suggests that they don’t help – and may actually worsen – outcomes.

Denise Fulton/MDedge News

In particular, this study looked at the impact of NSAIDs on synovitis – the inflammation of the membrane lining the knee joint – by using MRI-based structural biomarkers.

OA, the most common form of arthritis, affects more than 32 million adults in the United States and more than 500 million people worldwide.
 

No approved therapy to reduce OA progression

Little is known of the long-term effects of NSAIDs on OA progression. Currently, there’s no approved therapy to cure OA or to reduce its advance.

Dr. Luitjens noted, however, that the synovial membrane mediates development and progression of OA and may be a good therapeutic target.

Researchers studied participants from the Osteoarthritis Initiative (OAI) cohort with moderate to severe OA who used NSAIDs regularly for at least 1 year between baseline and 4-year follow-up. All participants had high-quality 3T MRI of the knee at baseline and after 4 years. Images were scored for biomarkers of inflammation, including cartilage thickness and composition.

Dr. Luitjens and associates studied 721 participants who matched the inclusion criteria (129 with and 592 participants without regular NSAID use). The available data did not further specify amounts of NSAIDs used.

At baseline, significantly higher signal intensity in the infrapatellar fat pad (IFP) was seen in patients who used NSAID, compared with controls (adjusted difference in score, 0.26; 95% confidence interval, –0.5 to –0.129; P = .039).

In addition, at the end of the study period, there was a significantly greater increase in signal intensity of IFP (adjusted difference in score, 0.46; 95% CI, 0.2-0.72; P < .001) and higher increase in effusion synovitis (adjusted difference in score, 0.27; 95% CI, 0.06-0.47;  P = .01) in NSAID users, compared with controls.

IFP size and synovial proliferation score did not different significantly between groups at the start of the study and showed no significant change over time.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared with the control group, and worsened at 4-year follow-up.

Design limits strength

Amanda E. Nelson, MD, associate professor of medicine, division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill, cautioned against assuming causality, pointing out that the OAI is an observational cohort study. (Dr. Nelson was not involved in the OAI or Dr. Luitjens’ analysis.)

“[The OAI is] large and well known, but it wasn’t designed to compare these groups, and this was a small subset,” she said in an interview. Without randomization, it’s hard to judge the results.

“It may be that people on NSAIDs for the duration of the study had more pain and had more disease to begin with, or had more symptoms or had failed other treatments,” she said, adding that the effect sizes were small.

Measures such as the IFP are ranked 0-3, so “the clinical difference of a 0.26 difference on a 0-3 scale is a bit uncertain,” she said.

Dr. Luitjens said that the researchers tried to adjust for potential confounders but agreed that randomized controlled trials are needed to better advise physicians and patients on the benefits or harms of using NSAIDs for OA.

Weighing the risks in older adults

Una Makris, MD, associate professor of internal medicine in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, noted that NSAIDs are “not always the safest option.”

“We are still in desperate need of disease-modifying drugs in OA with rigorous randomized trials to show efficacy for outcomes that are most meaningful to patients,” Dr. Makris, who was not involved in the study, told this news organization.

“OA is most common in older adults, those often with multiple comorbidities, so we must always weigh the risks – including known adverse effects which can be amplified in older adults – and benefits with the goal of improved function and less pain,” Dr. Makris said.

NSAID use also should be considered in the context of body mass index, cardiovascular risk, prior trauma or injury, other medication use, and behavioral factors, including physical activity, she said.

Dr. Luitjens, Dr. Nelson, and Dr. Makris reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

DENVER – As best practices for screening and surveillance of high-risk cutaneous squamous cell carcinoma (CSCC) continue to evolve, mounting evidence supports the use of radiologic imaging.

In a study published in 2020, Emily Ruiz, MD, MPH, and colleagues identified 87 CSCC tumors in 83 patients who underwent baseline or surveillance imaging primary at the Brigham and Women’s Hospital Mohs Surgery Clinic and the Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic, both in Boston, from Jan. 1, 2017, to June 1, 2019. Of the 87 primary CSCCs, 48 (58%) underwent surveillance imaging. The researchers found that imaging detected additional disease in 26 patients, or 30% of cases, “whether that be nodal metastasis, local invasion beyond what was clinically accepted, or in-transit disease,” Dr. Ruiz, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s, said during the annual meeting of the American Society for Dermatologic Surgery. “But if you look at the 16 nodal metastases in this cohort, all were picked up on imaging and not on clinical exam.”

Since publication of these results, Dr. Ruiz routinely considers baseline radiologic imaging in T2b and T3 tumors; borderline T2a tumors (which she said they are now calling “T2a high,” for those who have one risk factor plus another intermediate risk factor),” and T2a tumors in patients who are profoundly immunosuppressed.

“My preference is to always do [the imaging] before treatment unless I’m up-staging them during surgery,” said Dr. Ruiz, who also directs the High-Risk Skin Cancer Clinic at Dana Farber. “We have picked up nodal metastases before surgery, which enables us to create a good therapeutic plan for our patients before we start operating. Then we image them every 6 months or so for about 2 years. Sometimes we will extend that out to 3 years.”

Some clinicians use sentinel lymph node biopsy (SLNB) as a diagnostic test, but there are mixed results about its prognostic significance. A retrospective observational study of 720 patients with CSCC found that SLNB provided no benefit regarding further metastasis or tumor-specific survival, compared with those who received routine observation and follow-up, “but head and neck surgeons in the U.S. are putting together some prospective data from multiple centers,” Dr. Ruiz said. “I think in the coming years, you will have more multicenter data to inform us as to whether to do SLNB or not.”

Surgery may be the mainstay of treatment for resectable SCC, but the emerging role of neoadjuvant therapeutics is changing the way oncologists treat these tumors. For example, in a phase 2 trial recently published in the New England Journal of Medicine, 79 patients with stage II-IV CSCC received up to four doses of immunotherapy with the programmed death receptor–1 (PD-1) blocker cemiplimab administered every 3 weeks. The primary endpoint was a pathologic complete response, defined as the absence of viable tumor cells in the surgical specimen at a central laboratory. The researchers observed that 68% of patients had an objective response.

“These were patients with localized tumors that were either very aggressive or had nodal metastases,” said Dr, Ruiz, who was the site primary investigator at Dana Farber and a coauthor of the NEJM study. “This has altered the way we approach treating our larger tumors that could be resectable but have a lot of disease either locally or in the nodal basin. We think that we can shrink down the tumor and make it easier to resect, but also there is the possibility or improving outcomes.”

At Brigham and Women’s and the Dana Farber, she and her colleagues consider immunotherapy for multiple recurrent tumors that have been previously irradiated; cases of large tumor burden locally or in the nodal basin; tumors that have a complex surgical plan; cases where there is a low likelihood of achieving clear surgical margins; and cases of in-transit disease.

“We use two to four doses of immunotherapy prior to surgery and assess the tumor response after two doses both clinically and radiologically,” she said. “If the tumor continues to grow, we would do surgery sooner.”

The side-effect profile of immunotherapy is another consideration. “Some patients are not appropriate for a neoadjuvant immunotherapy approach, such as transplant patients,” she said.

According to the latest National Comprehensive Cancer Network guidelines, surgery with or without adjuvant radiation is the current standard of care for treating CSCC. These guidelines were developed without much data to support the use of radiation, but a 20-year retrospective cohort study at Brigham and Women’s Hospital and the Cleveland Clinic Foundation found that adjuvant radiation following margin resection in high T-stage CSCC cut the risk of local and locoregional recurrence in half.

“This is something that radiation oncologists have told us for years, but there was no data to support it, so it was nice to see that borne out in clinical data,” said Dr. Ruiz, the study’s lead author. The 10% risk of local recurrence observed in the study “may not be high enough for some of our older patients, so we wanted to see if we could identify a group of high tumors that had higher risk of local recurrence,” she said. They found that patients who had a greater than 20% risk of poor outcome were those with recurrent tumors, those with tumors 6 cm or greater in size, and those with all four BWH risk factors (tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, or tumor invasion beyond fat excluding bone invasion).

“Those risks were also cut in half if you added radiation,” she said. “So, the way I now approach counseling patients is, I try to estimate their baseline risk as best I can based on the tumor itself. I tell them that if they want to do adjuvant radiation it would cut the risk in half. Some patients are too frail and want to pass on it, while others are very interested.”

Of patients who did not receive radiation but had a disease recurrence, just under half of tumors were salvageable, about 25% died of their disease, and 23% had persistent disease. “I think this does support using radiation earlier on for the appropriate patient,” Dr. Ruiz said. “I consider the baseline risks [and] balance that with the patient’s comorbidities.”

Limited data exists on adjuvant immunotherapy for CSCC, but two ongoing randomized prospective clinical trials underway are studying the PD-1 inhibitors cemiplimab and pembrolizumab versus placebo. “We don’t have data yet, but prior to randomization, patients undergo surgery with macroscopic gross resection of all disease,” Dr. Ruiz said. “All tumors receive ART [adjuvant radiation therapy] prior to randomization”

Dr. Ruiz disclosed that she is a consultant for Sanofi, Regeneron, Genentech, and Jaunce Therapeutics. She is also a member of the advisory board for Checkpoint Therapeutics and is an investigator for Merck, Sanofi, and Regeneron.

DENVER – As best practices for screening and surveillance of high-risk cutaneous squamous cell carcinoma (CSCC) continue to evolve, mounting evidence supports the use of radiologic imaging.

In a study published in 2020, Emily Ruiz, MD, MPH, and colleagues identified 87 CSCC tumors in 83 patients who underwent baseline or surveillance imaging primary at the Brigham and Women’s Hospital Mohs Surgery Clinic and the Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic, both in Boston, from Jan. 1, 2017, to June 1, 2019. Of the 87 primary CSCCs, 48 (58%) underwent surveillance imaging. The researchers found that imaging detected additional disease in 26 patients, or 30% of cases, “whether that be nodal metastasis, local invasion beyond what was clinically accepted, or in-transit disease,” Dr. Ruiz, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s, said during the annual meeting of the American Society for Dermatologic Surgery. “But if you look at the 16 nodal metastases in this cohort, all were picked up on imaging and not on clinical exam.”

Since publication of these results, Dr. Ruiz routinely considers baseline radiologic imaging in T2b and T3 tumors; borderline T2a tumors (which she said they are now calling “T2a high,” for those who have one risk factor plus another intermediate risk factor),” and T2a tumors in patients who are profoundly immunosuppressed.

“My preference is to always do [the imaging] before treatment unless I’m up-staging them during surgery,” said Dr. Ruiz, who also directs the High-Risk Skin Cancer Clinic at Dana Farber. “We have picked up nodal metastases before surgery, which enables us to create a good therapeutic plan for our patients before we start operating. Then we image them every 6 months or so for about 2 years. Sometimes we will extend that out to 3 years.”

Some clinicians use sentinel lymph node biopsy (SLNB) as a diagnostic test, but there are mixed results about its prognostic significance. A retrospective observational study of 720 patients with CSCC found that SLNB provided no benefit regarding further metastasis or tumor-specific survival, compared with those who received routine observation and follow-up, “but head and neck surgeons in the U.S. are putting together some prospective data from multiple centers,” Dr. Ruiz said. “I think in the coming years, you will have more multicenter data to inform us as to whether to do SLNB or not.”

Surgery may be the mainstay of treatment for resectable SCC, but the emerging role of neoadjuvant therapeutics is changing the way oncologists treat these tumors. For example, in a phase 2 trial recently published in the New England Journal of Medicine, 79 patients with stage II-IV CSCC received up to four doses of immunotherapy with the programmed death receptor–1 (PD-1) blocker cemiplimab administered every 3 weeks. The primary endpoint was a pathologic complete response, defined as the absence of viable tumor cells in the surgical specimen at a central laboratory. The researchers observed that 68% of patients had an objective response.

“These were patients with localized tumors that were either very aggressive or had nodal metastases,” said Dr, Ruiz, who was the site primary investigator at Dana Farber and a coauthor of the NEJM study. “This has altered the way we approach treating our larger tumors that could be resectable but have a lot of disease either locally or in the nodal basin. We think that we can shrink down the tumor and make it easier to resect, but also there is the possibility or improving outcomes.”

At Brigham and Women’s and the Dana Farber, she and her colleagues consider immunotherapy for multiple recurrent tumors that have been previously irradiated; cases of large tumor burden locally or in the nodal basin; tumors that have a complex surgical plan; cases where there is a low likelihood of achieving clear surgical margins; and cases of in-transit disease.

“We use two to four doses of immunotherapy prior to surgery and assess the tumor response after two doses both clinically and radiologically,” she said. “If the tumor continues to grow, we would do surgery sooner.”

The side-effect profile of immunotherapy is another consideration. “Some patients are not appropriate for a neoadjuvant immunotherapy approach, such as transplant patients,” she said.

According to the latest National Comprehensive Cancer Network guidelines, surgery with or without adjuvant radiation is the current standard of care for treating CSCC. These guidelines were developed without much data to support the use of radiation, but a 20-year retrospective cohort study at Brigham and Women’s Hospital and the Cleveland Clinic Foundation found that adjuvant radiation following margin resection in high T-stage CSCC cut the risk of local and locoregional recurrence in half.

“This is something that radiation oncologists have told us for years, but there was no data to support it, so it was nice to see that borne out in clinical data,” said Dr. Ruiz, the study’s lead author. The 10% risk of local recurrence observed in the study “may not be high enough for some of our older patients, so we wanted to see if we could identify a group of high tumors that had higher risk of local recurrence,” she said. They found that patients who had a greater than 20% risk of poor outcome were those with recurrent tumors, those with tumors 6 cm or greater in size, and those with all four BWH risk factors (tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, or tumor invasion beyond fat excluding bone invasion).

“Those risks were also cut in half if you added radiation,” she said. “So, the way I now approach counseling patients is, I try to estimate their baseline risk as best I can based on the tumor itself. I tell them that if they want to do adjuvant radiation it would cut the risk in half. Some patients are too frail and want to pass on it, while others are very interested.”

Of patients who did not receive radiation but had a disease recurrence, just under half of tumors were salvageable, about 25% died of their disease, and 23% had persistent disease. “I think this does support using radiation earlier on for the appropriate patient,” Dr. Ruiz said. “I consider the baseline risks [and] balance that with the patient’s comorbidities.”

Limited data exists on adjuvant immunotherapy for CSCC, but two ongoing randomized prospective clinical trials underway are studying the PD-1 inhibitors cemiplimab and pembrolizumab versus placebo. “We don’t have data yet, but prior to randomization, patients undergo surgery with macroscopic gross resection of all disease,” Dr. Ruiz said. “All tumors receive ART [adjuvant radiation therapy] prior to randomization”

Dr. Ruiz disclosed that she is a consultant for Sanofi, Regeneron, Genentech, and Jaunce Therapeutics. She is also a member of the advisory board for Checkpoint Therapeutics and is an investigator for Merck, Sanofi, and Regeneron.

DENVER – As best practices for screening and surveillance of high-risk cutaneous squamous cell carcinoma (CSCC) continue to evolve, mounting evidence supports the use of radiologic imaging.

In a study published in 2020, Emily Ruiz, MD, MPH, and colleagues identified 87 CSCC tumors in 83 patients who underwent baseline or surveillance imaging primary at the Brigham and Women’s Hospital Mohs Surgery Clinic and the Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic, both in Boston, from Jan. 1, 2017, to June 1, 2019. Of the 87 primary CSCCs, 48 (58%) underwent surveillance imaging. The researchers found that imaging detected additional disease in 26 patients, or 30% of cases, “whether that be nodal metastasis, local invasion beyond what was clinically accepted, or in-transit disease,” Dr. Ruiz, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s, said during the annual meeting of the American Society for Dermatologic Surgery. “But if you look at the 16 nodal metastases in this cohort, all were picked up on imaging and not on clinical exam.”

Since publication of these results, Dr. Ruiz routinely considers baseline radiologic imaging in T2b and T3 tumors; borderline T2a tumors (which she said they are now calling “T2a high,” for those who have one risk factor plus another intermediate risk factor),” and T2a tumors in patients who are profoundly immunosuppressed.

“My preference is to always do [the imaging] before treatment unless I’m up-staging them during surgery,” said Dr. Ruiz, who also directs the High-Risk Skin Cancer Clinic at Dana Farber. “We have picked up nodal metastases before surgery, which enables us to create a good therapeutic plan for our patients before we start operating. Then we image them every 6 months or so for about 2 years. Sometimes we will extend that out to 3 years.”

Some clinicians use sentinel lymph node biopsy (SLNB) as a diagnostic test, but there are mixed results about its prognostic significance. A retrospective observational study of 720 patients with CSCC found that SLNB provided no benefit regarding further metastasis or tumor-specific survival, compared with those who received routine observation and follow-up, “but head and neck surgeons in the U.S. are putting together some prospective data from multiple centers,” Dr. Ruiz said. “I think in the coming years, you will have more multicenter data to inform us as to whether to do SLNB or not.”

Surgery may be the mainstay of treatment for resectable SCC, but the emerging role of neoadjuvant therapeutics is changing the way oncologists treat these tumors. For example, in a phase 2 trial recently published in the New England Journal of Medicine, 79 patients with stage II-IV CSCC received up to four doses of immunotherapy with the programmed death receptor–1 (PD-1) blocker cemiplimab administered every 3 weeks. The primary endpoint was a pathologic complete response, defined as the absence of viable tumor cells in the surgical specimen at a central laboratory. The researchers observed that 68% of patients had an objective response.

“These were patients with localized tumors that were either very aggressive or had nodal metastases,” said Dr, Ruiz, who was the site primary investigator at Dana Farber and a coauthor of the NEJM study. “This has altered the way we approach treating our larger tumors that could be resectable but have a lot of disease either locally or in the nodal basin. We think that we can shrink down the tumor and make it easier to resect, but also there is the possibility or improving outcomes.”

At Brigham and Women’s and the Dana Farber, she and her colleagues consider immunotherapy for multiple recurrent tumors that have been previously irradiated; cases of large tumor burden locally or in the nodal basin; tumors that have a complex surgical plan; cases where there is a low likelihood of achieving clear surgical margins; and cases of in-transit disease.

“We use two to four doses of immunotherapy prior to surgery and assess the tumor response after two doses both clinically and radiologically,” she said. “If the tumor continues to grow, we would do surgery sooner.”

The side-effect profile of immunotherapy is another consideration. “Some patients are not appropriate for a neoadjuvant immunotherapy approach, such as transplant patients,” she said.

According to the latest National Comprehensive Cancer Network guidelines, surgery with or without adjuvant radiation is the current standard of care for treating CSCC. These guidelines were developed without much data to support the use of radiation, but a 20-year retrospective cohort study at Brigham and Women’s Hospital and the Cleveland Clinic Foundation found that adjuvant radiation following margin resection in high T-stage CSCC cut the risk of local and locoregional recurrence in half.

“This is something that radiation oncologists have told us for years, but there was no data to support it, so it was nice to see that borne out in clinical data,” said Dr. Ruiz, the study’s lead author. The 10% risk of local recurrence observed in the study “may not be high enough for some of our older patients, so we wanted to see if we could identify a group of high tumors that had higher risk of local recurrence,” she said. They found that patients who had a greater than 20% risk of poor outcome were those with recurrent tumors, those with tumors 6 cm or greater in size, and those with all four BWH risk factors (tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, or tumor invasion beyond fat excluding bone invasion).

“Those risks were also cut in half if you added radiation,” she said. “So, the way I now approach counseling patients is, I try to estimate their baseline risk as best I can based on the tumor itself. I tell them that if they want to do adjuvant radiation it would cut the risk in half. Some patients are too frail and want to pass on it, while others are very interested.”

Of patients who did not receive radiation but had a disease recurrence, just under half of tumors were salvageable, about 25% died of their disease, and 23% had persistent disease. “I think this does support using radiation earlier on for the appropriate patient,” Dr. Ruiz said. “I consider the baseline risks [and] balance that with the patient’s comorbidities.”

Limited data exists on adjuvant immunotherapy for CSCC, but two ongoing randomized prospective clinical trials underway are studying the PD-1 inhibitors cemiplimab and pembrolizumab versus placebo. “We don’t have data yet, but prior to randomization, patients undergo surgery with macroscopic gross resection of all disease,” Dr. Ruiz said. “All tumors receive ART [adjuvant radiation therapy] prior to randomization”

Dr. Ruiz disclosed that she is a consultant for Sanofi, Regeneron, Genentech, and Jaunce Therapeutics. She is also a member of the advisory board for Checkpoint Therapeutics and is an investigator for Merck, Sanofi, and Regeneron.

The safety of vaginal breech delivery has been controversial since the Term Breech Trial in 2000 suggested increased neonatal mortality and short-term morbidity associated with vaginal breech delivery. The stance against breech delivery has softened since that time. Fruscalzo and colleagues provide yet more evidence supporting the safety of vaginal breech deliveries with their single-center, retrospective study, which included 804 singleton pregnant women who underwent vaginal breech vs emergency cesarean section vs elective cesarean section in Coesfeld, Germany. They found no significant differences between the vaginal breech–delivery group vs the other two groups in regard to umbilical artery pH < 7, low Apgar scores, or neonatal intensive care unit admissions. The only significant difference noted was umbilical artery pH < 7.1. This suggests that in experienced hands (each of the candidates was referred to a senior obstetrician for consultation), vaginal breech delivery can be safe, including for nulliparous women (67% were nulliparous), showing that even the short-term morbidity associated with vaginal breech delivery approaches that of planned cesarean section.

Two other articles raise caution regarding SD and increased risk for fetal death and PPH. Linde and colleagues used data from The Medical Birth Registry of Norway and Statistics Norway to examine recurrence risk for PPH associated with various causes. PPH associated with SD led the way: The recurrence risk adjusted odds ratio (aOR) was 6.8 for SD vs 5.9 for retained products of conception, 4.0 for uterine atony, 3.9 for obstetric trauma, and 2.2 for PPH of undefined cause. This study suggests that the risks for SD recurrence should be focused not just on SD, but also on PPH. Another concern regarding shoulder dystocia is raised by Davidesko and colleagues in their analysis of risk factors for intrapartum fetal death. Using a generalized estimation equation model to help identify independent risk factors for intrapartum fetal death, they examined 344,536 deliveries from 1991 to 2016 at Soroka University Medical Center in Israel and noted that SD again led the way: aOR was 23.8 for SD vs 19.0 for uterine rupture, 11.9 for preterm birth, 6.2 for placental abruption, and 3.6 for fetal malpresentation. This high risk for intrapartum fetal death associated with SD suggests a need for even more robust SD drills to help deal with this dreaded and often unpredictable obstetric emergency.

The safety of vaginal breech delivery has been controversial since the Term Breech Trial in 2000 suggested increased neonatal mortality and short-term morbidity associated with vaginal breech delivery. The stance against breech delivery has softened since that time. Fruscalzo and colleagues provide yet more evidence supporting the safety of vaginal breech deliveries with their single-center, retrospective study, which included 804 singleton pregnant women who underwent vaginal breech vs emergency cesarean section vs elective cesarean section in Coesfeld, Germany. They found no significant differences between the vaginal breech–delivery group vs the other two groups in regard to umbilical artery pH < 7, low Apgar scores, or neonatal intensive care unit admissions. The only significant difference noted was umbilical artery pH < 7.1. This suggests that in experienced hands (each of the candidates was referred to a senior obstetrician for consultation), vaginal breech delivery can be safe, including for nulliparous women (67% were nulliparous), showing that even the short-term morbidity associated with vaginal breech delivery approaches that of planned cesarean section.

Two other articles raise caution regarding SD and increased risk for fetal death and PPH. Linde and colleagues used data from The Medical Birth Registry of Norway and Statistics Norway to examine recurrence risk for PPH associated with various causes. PPH associated with SD led the way: The recurrence risk adjusted odds ratio (aOR) was 6.8 for SD vs 5.9 for retained products of conception, 4.0 for uterine atony, 3.9 for obstetric trauma, and 2.2 for PPH of undefined cause. This study suggests that the risks for SD recurrence should be focused not just on SD, but also on PPH. Another concern regarding shoulder dystocia is raised by Davidesko and colleagues in their analysis of risk factors for intrapartum fetal death. Using a generalized estimation equation model to help identify independent risk factors for intrapartum fetal death, they examined 344,536 deliveries from 1991 to 2016 at Soroka University Medical Center in Israel and noted that SD again led the way: aOR was 23.8 for SD vs 19.0 for uterine rupture, 11.9 for preterm birth, 6.2 for placental abruption, and 3.6 for fetal malpresentation. This high risk for intrapartum fetal death associated with SD suggests a need for even more robust SD drills to help deal with this dreaded and often unpredictable obstetric emergency.

The safety of vaginal breech delivery has been controversial since the Term Breech Trial in 2000 suggested increased neonatal mortality and short-term morbidity associated with vaginal breech delivery. The stance against breech delivery has softened since that time. Fruscalzo and colleagues provide yet more evidence supporting the safety of vaginal breech deliveries with their single-center, retrospective study, which included 804 singleton pregnant women who underwent vaginal breech vs emergency cesarean section vs elective cesarean section in Coesfeld, Germany. They found no significant differences between the vaginal breech–delivery group vs the other two groups in regard to umbilical artery pH < 7, low Apgar scores, or neonatal intensive care unit admissions. The only significant difference noted was umbilical artery pH < 7.1. This suggests that in experienced hands (each of the candidates was referred to a senior obstetrician for consultation), vaginal breech delivery can be safe, including for nulliparous women (67% were nulliparous), showing that even the short-term morbidity associated with vaginal breech delivery approaches that of planned cesarean section.

Two other articles raise caution regarding SD and increased risk for fetal death and PPH. Linde and colleagues used data from The Medical Birth Registry of Norway and Statistics Norway to examine recurrence risk for PPH associated with various causes. PPH associated with SD led the way: The recurrence risk adjusted odds ratio (aOR) was 6.8 for SD vs 5.9 for retained products of conception, 4.0 for uterine atony, 3.9 for obstetric trauma, and 2.2 for PPH of undefined cause. This study suggests that the risks for SD recurrence should be focused not just on SD, but also on PPH. Another concern regarding shoulder dystocia is raised by Davidesko and colleagues in their analysis of risk factors for intrapartum fetal death. Using a generalized estimation equation model to help identify independent risk factors for intrapartum fetal death, they examined 344,536 deliveries from 1991 to 2016 at Soroka University Medical Center in Israel and noted that SD again led the way: aOR was 23.8 for SD vs 19.0 for uterine rupture, 11.9 for preterm birth, 6.2 for placental abruption, and 3.6 for fetal malpresentation. This high risk for intrapartum fetal death associated with SD suggests a need for even more robust SD drills to help deal with this dreaded and often unpredictable obstetric emergency.

Nano-pulse stimulation has emerged as a promising treatment option for sebaceous hyperplasia, warts, and other dermal lesions without the use of heat.

During a virtual course on laser and aesthetic skin therapy, Yakir Levin, MD, PhD, likened nano-pulse stimulation to microneedling or radiofrequency microneedling “in that you have an array of microneedles that go into the skin,” he said. “However, it is actually completely different.”

The CellFX System uses nano-pulse stimulation to deliver ultrashort electrical energy pulses into the skin of target lesions via a console-based handheld applicator. In September 2022, the Food and Drug Administration cleared the CellFX system for treatment of sebaceous hyperplasia in patients with Fitzpatrick skin types I-II. This followed a general clearance of the device in 2021 for dermatologic procedures requiring ablation and resurfacing of the skin.

Pulses from the device deliver a “constant electrical potential gradient across cell membranes and organelle membranes, causing them to break down,” explained Dr. Levin, a dermatologist and physician scientist at Massachusetts General Hospital, Boston, where he practices cosmetic dermatology and conducts research on birthmarks in children. This creates pores in those membranes “and leads to a controlled form of cell death,” he said. “As a result, this treatment is limited to cells, so you can do it in the dermis without damaging the collagen network. It spares tissue that’s outside of the field, and it’s nonthermal.”

Images from electron microscopy have demonstrated swelling of the mitochondria and breakdown of nuclei within 2 hours of treatment in a rat study. “Within 1 day of treatment you have death of the cells and the beginning of involution of the lesion,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “This presents us with the opportunity to treat dermal lesions without causing damage to the epidermis or to the acellular portion of the dermis.”

In published studies, nano-pulse stimulation has been shown to be effective for treating sebaceous hyperplasia and warts. According to Dr. Levin, clinicians typically treat sebaceous hyperplasia with an radiofrequency microneedle or electrodesiccation, “where we shave off the top but do not try to hit the bottom because we don’t want to cause scarring of the dermis,” he said. “Using the nano-pulse stimulation technology, however, you end up with involution of the sebaceous lesion without damaging the surrounding dermis.”

In a prospective, randomized study, 72 individuals with sebaceous gland hyperplasia received nano-pulse stimulation to 222 lesions and they returned for three to four follow-up evaluations with photographs. At the final study visit, investigators rated 99.6% of the sebaceous gland lesions as clear or mostly clear, while 79% of the study participants said they were “satisfied” or “mostly satisfied” with the outcome.

At posttreatment day 60, 55% of the lesions were judged to have no hyperpigmentation and 31% exhibited mild posttreatment hyperpigmentation.

In a more recent study, researchers used the CellFX System to treat 195 cutaneous warts up to 10 mm wide in 62 individuals enrolled at one of five sites. They found that 75% of common warts, 73% of flat warts, and 44% of plantar warts were completely clear 60 days following the last nano-pulse stimulation treatment and did not recur within the 120-day observation period.

The most common reactions at the treatment sites were erythema (51%) and eschar formation (23%) on day 30.

According to Dr. Levin, promising future applications of nano-pulse stimulation include treatment of syringomas, dermatofibromas, and basal cell carcinomas.

Dr. Levin reported financial interest in Accure Acne, Avava Medical, and Soltego. The CellFX system was developed and is marketed by Pulse Biosciences.

Nano-pulse stimulation has emerged as a promising treatment option for sebaceous hyperplasia, warts, and other dermal lesions without the use of heat.

During a virtual course on laser and aesthetic skin therapy, Yakir Levin, MD, PhD, likened nano-pulse stimulation to microneedling or radiofrequency microneedling “in that you have an array of microneedles that go into the skin,” he said. “However, it is actually completely different.”

The CellFX System uses nano-pulse stimulation to deliver ultrashort electrical energy pulses into the skin of target lesions via a console-based handheld applicator. In September 2022, the Food and Drug Administration cleared the CellFX system for treatment of sebaceous hyperplasia in patients with Fitzpatrick skin types I-II. This followed a general clearance of the device in 2021 for dermatologic procedures requiring ablation and resurfacing of the skin.

Pulses from the device deliver a “constant electrical potential gradient across cell membranes and organelle membranes, causing them to break down,” explained Dr. Levin, a dermatologist and physician scientist at Massachusetts General Hospital, Boston, where he practices cosmetic dermatology and conducts research on birthmarks in children. This creates pores in those membranes “and leads to a controlled form of cell death,” he said. “As a result, this treatment is limited to cells, so you can do it in the dermis without damaging the collagen network. It spares tissue that’s outside of the field, and it’s nonthermal.”

Images from electron microscopy have demonstrated swelling of the mitochondria and breakdown of nuclei within 2 hours of treatment in a rat study. “Within 1 day of treatment you have death of the cells and the beginning of involution of the lesion,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “This presents us with the opportunity to treat dermal lesions without causing damage to the epidermis or to the acellular portion of the dermis.”

In published studies, nano-pulse stimulation has been shown to be effective for treating sebaceous hyperplasia and warts. According to Dr. Levin, clinicians typically treat sebaceous hyperplasia with an radiofrequency microneedle or electrodesiccation, “where we shave off the top but do not try to hit the bottom because we don’t want to cause scarring of the dermis,” he said. “Using the nano-pulse stimulation technology, however, you end up with involution of the sebaceous lesion without damaging the surrounding dermis.”

In a prospective, randomized study, 72 individuals with sebaceous gland hyperplasia received nano-pulse stimulation to 222 lesions and they returned for three to four follow-up evaluations with photographs. At the final study visit, investigators rated 99.6% of the sebaceous gland lesions as clear or mostly clear, while 79% of the study participants said they were “satisfied” or “mostly satisfied” with the outcome.

At posttreatment day 60, 55% of the lesions were judged to have no hyperpigmentation and 31% exhibited mild posttreatment hyperpigmentation.

In a more recent study, researchers used the CellFX System to treat 195 cutaneous warts up to 10 mm wide in 62 individuals enrolled at one of five sites. They found that 75% of common warts, 73% of flat warts, and 44% of plantar warts were completely clear 60 days following the last nano-pulse stimulation treatment and did not recur within the 120-day observation period.

The most common reactions at the treatment sites were erythema (51%) and eschar formation (23%) on day 30.

According to Dr. Levin, promising future applications of nano-pulse stimulation include treatment of syringomas, dermatofibromas, and basal cell carcinomas.

Dr. Levin reported financial interest in Accure Acne, Avava Medical, and Soltego. The CellFX system was developed and is marketed by Pulse Biosciences.

Nano-pulse stimulation has emerged as a promising treatment option for sebaceous hyperplasia, warts, and other dermal lesions without the use of heat.

During a virtual course on laser and aesthetic skin therapy, Yakir Levin, MD, PhD, likened nano-pulse stimulation to microneedling or radiofrequency microneedling “in that you have an array of microneedles that go into the skin,” he said. “However, it is actually completely different.”

The CellFX System uses nano-pulse stimulation to deliver ultrashort electrical energy pulses into the skin of target lesions via a console-based handheld applicator. In September 2022, the Food and Drug Administration cleared the CellFX system for treatment of sebaceous hyperplasia in patients with Fitzpatrick skin types I-II. This followed a general clearance of the device in 2021 for dermatologic procedures requiring ablation and resurfacing of the skin.

Pulses from the device deliver a “constant electrical potential gradient across cell membranes and organelle membranes, causing them to break down,” explained Dr. Levin, a dermatologist and physician scientist at Massachusetts General Hospital, Boston, where he practices cosmetic dermatology and conducts research on birthmarks in children. This creates pores in those membranes “and leads to a controlled form of cell death,” he said. “As a result, this treatment is limited to cells, so you can do it in the dermis without damaging the collagen network. It spares tissue that’s outside of the field, and it’s nonthermal.”

Images from electron microscopy have demonstrated swelling of the mitochondria and breakdown of nuclei within 2 hours of treatment in a rat study. “Within 1 day of treatment you have death of the cells and the beginning of involution of the lesion,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “This presents us with the opportunity to treat dermal lesions without causing damage to the epidermis or to the acellular portion of the dermis.”

In published studies, nano-pulse stimulation has been shown to be effective for treating sebaceous hyperplasia and warts. According to Dr. Levin, clinicians typically treat sebaceous hyperplasia with an radiofrequency microneedle or electrodesiccation, “where we shave off the top but do not try to hit the bottom because we don’t want to cause scarring of the dermis,” he said. “Using the nano-pulse stimulation technology, however, you end up with involution of the sebaceous lesion without damaging the surrounding dermis.”

In a prospective, randomized study, 72 individuals with sebaceous gland hyperplasia received nano-pulse stimulation to 222 lesions and they returned for three to four follow-up evaluations with photographs. At the final study visit, investigators rated 99.6% of the sebaceous gland lesions as clear or mostly clear, while 79% of the study participants said they were “satisfied” or “mostly satisfied” with the outcome.

At posttreatment day 60, 55% of the lesions were judged to have no hyperpigmentation and 31% exhibited mild posttreatment hyperpigmentation.

In a more recent study, researchers used the CellFX System to treat 195 cutaneous warts up to 10 mm wide in 62 individuals enrolled at one of five sites. They found that 75% of common warts, 73% of flat warts, and 44% of plantar warts were completely clear 60 days following the last nano-pulse stimulation treatment and did not recur within the 120-day observation period.

The most common reactions at the treatment sites were erythema (51%) and eschar formation (23%) on day 30.

According to Dr. Levin, promising future applications of nano-pulse stimulation include treatment of syringomas, dermatofibromas, and basal cell carcinomas.

Dr. Levin reported financial interest in Accure Acne, Avava Medical, and Soltego. The CellFX system was developed and is marketed by Pulse Biosciences.

You can get all the exercise you need in just 8 minutes a day if you work out a bit harder, according to a new study in the European Heart Journal.

Just 54 minutes of vigorous exercise per week provides the most bang for your buck, researchers found, lowering the risk of early death from any cause by 36%, and your chances of getting heart disease by 35%.

Scientists examined data from fitness trackers worn by more than 71,000 people studied in the United Kingdom, then analyzed their health over the next several years.

While more time spent exercising unsurprisingly led to better health, the protective effects of exercise start to plateau after a certain point, according to the study.

A tough, short workout improves blood pressure, shrinks artery-clogging plaques, and boosts your overall fitness.

Vigorous exercise helps your body adapt better than moderate exercise does, leading to more notable benefits, says study author Matthew Ahmadi, PhD, a postdoctoral research fellow at the University of Sydney.

“Collectively, these will lower a person’s risk of cardiovascular disease. Exercise can also lower body inflammation, which will in turn lower the risk for certain cancers,” he says.

The CDC recommends at least 150 minutes of “moderate intensity” exercise each week, such as walking at a brisk pace. Or you could spend 75 minutes each week doing vigorous exercise, like running, it says. The CDC also recommends muscle strengthening activities, like lifting weights, at least 2 days per week.

But only 54% of Americans actually manage to get their 150 minutes of aerobic activity in each week, according to the most recent data from the National Center for Health Statistics. Even fewer – just 24% – also squeeze in the two recommended strength workouts.

So 8 minutes a day instead of 30 minutes could persuade busy people to get the exercise they need.

“Lack of time is one of the main reasons people have reported for not engaging in exercise,” says Dr. Ahmadi.

Vigorous exercise doesn’t mean you have to run, bike, or lift weights. Scientists consider a physical activity “vigorous” if it’s greater than 6 times your resting metabolic rate, or MET. That includes all kinds of strenuous movement, including dancing in a nightclub or carrying groceries upstairs.

“All of these activities are equally beneficial,” says Dr. Ahmadi.

He recommends aiming for 2-minute bouts of a heart-pumping activity, spread throughout the day for the most benefit in the least amount of time. If you wear a smartwatch or other device that tracks your heart rate, you’ll be above the threshold if your heart is pumping at 77% or more of your max heart rate (which most fitness trackers help you calculate).

No smartwatch? “The easiest way a person can infer if they are doing vigorous activity is if they are breathing hard enough that it’s difficult to have a conversation or speak in a full sentence while doing the activity,” Dr. Ahmadi says. In other words, if you’re huffing and puffing, then you’re in the zone.

A version of this article first appeared on WebMD.com.

You can get all the exercise you need in just 8 minutes a day if you work out a bit harder, according to a new study in the European Heart Journal.

Just 54 minutes of vigorous exercise per week provides the most bang for your buck, researchers found, lowering the risk of early death from any cause by 36%, and your chances of getting heart disease by 35%.

Scientists examined data from fitness trackers worn by more than 71,000 people studied in the United Kingdom, then analyzed their health over the next several years.

While more time spent exercising unsurprisingly led to better health, the protective effects of exercise start to plateau after a certain point, according to the study.

A tough, short workout improves blood pressure, shrinks artery-clogging plaques, and boosts your overall fitness.

Vigorous exercise helps your body adapt better than moderate exercise does, leading to more notable benefits, says study author Matthew Ahmadi, PhD, a postdoctoral research fellow at the University of Sydney.

“Collectively, these will lower a person’s risk of cardiovascular disease. Exercise can also lower body inflammation, which will in turn lower the risk for certain cancers,” he says.

The CDC recommends at least 150 minutes of “moderate intensity” exercise each week, such as walking at a brisk pace. Or you could spend 75 minutes each week doing vigorous exercise, like running, it says. The CDC also recommends muscle strengthening activities, like lifting weights, at least 2 days per week.

But only 54% of Americans actually manage to get their 150 minutes of aerobic activity in each week, according to the most recent data from the National Center for Health Statistics. Even fewer – just 24% – also squeeze in the two recommended strength workouts.

So 8 minutes a day instead of 30 minutes could persuade busy people to get the exercise they need.

“Lack of time is one of the main reasons people have reported for not engaging in exercise,” says Dr. Ahmadi.

Vigorous exercise doesn’t mean you have to run, bike, or lift weights. Scientists consider a physical activity “vigorous” if it’s greater than 6 times your resting metabolic rate, or MET. That includes all kinds of strenuous movement, including dancing in a nightclub or carrying groceries upstairs.

“All of these activities are equally beneficial,” says Dr. Ahmadi.

He recommends aiming for 2-minute bouts of a heart-pumping activity, spread throughout the day for the most benefit in the least amount of time. If you wear a smartwatch or other device that tracks your heart rate, you’ll be above the threshold if your heart is pumping at 77% or more of your max heart rate (which most fitness trackers help you calculate).

No smartwatch? “The easiest way a person can infer if they are doing vigorous activity is if they are breathing hard enough that it’s difficult to have a conversation or speak in a full sentence while doing the activity,” Dr. Ahmadi says. In other words, if you’re huffing and puffing, then you’re in the zone.

A version of this article first appeared on WebMD.com.

You can get all the exercise you need in just 8 minutes a day if you work out a bit harder, according to a new study in the European Heart Journal.

Just 54 minutes of vigorous exercise per week provides the most bang for your buck, researchers found, lowering the risk of early death from any cause by 36%, and your chances of getting heart disease by 35%.

Scientists examined data from fitness trackers worn by more than 71,000 people studied in the United Kingdom, then analyzed their health over the next several years.

While more time spent exercising unsurprisingly led to better health, the protective effects of exercise start to plateau after a certain point, according to the study.

A tough, short workout improves blood pressure, shrinks artery-clogging plaques, and boosts your overall fitness.

Vigorous exercise helps your body adapt better than moderate exercise does, leading to more notable benefits, says study author Matthew Ahmadi, PhD, a postdoctoral research fellow at the University of Sydney.

“Collectively, these will lower a person’s risk of cardiovascular disease. Exercise can also lower body inflammation, which will in turn lower the risk for certain cancers,” he says.

The CDC recommends at least 150 minutes of “moderate intensity” exercise each week, such as walking at a brisk pace. Or you could spend 75 minutes each week doing vigorous exercise, like running, it says. The CDC also recommends muscle strengthening activities, like lifting weights, at least 2 days per week.

But only 54% of Americans actually manage to get their 150 minutes of aerobic activity in each week, according to the most recent data from the National Center for Health Statistics. Even fewer – just 24% – also squeeze in the two recommended strength workouts.

So 8 minutes a day instead of 30 minutes could persuade busy people to get the exercise they need.

“Lack of time is one of the main reasons people have reported for not engaging in exercise,” says Dr. Ahmadi.

Vigorous exercise doesn’t mean you have to run, bike, or lift weights. Scientists consider a physical activity “vigorous” if it’s greater than 6 times your resting metabolic rate, or MET. That includes all kinds of strenuous movement, including dancing in a nightclub or carrying groceries upstairs.

“All of these activities are equally beneficial,” says Dr. Ahmadi.

He recommends aiming for 2-minute bouts of a heart-pumping activity, spread throughout the day for the most benefit in the least amount of time. If you wear a smartwatch or other device that tracks your heart rate, you’ll be above the threshold if your heart is pumping at 77% or more of your max heart rate (which most fitness trackers help you calculate).

No smartwatch? “The easiest way a person can infer if they are doing vigorous activity is if they are breathing hard enough that it’s difficult to have a conversation or speak in a full sentence while doing the activity,” Dr. Ahmadi says. In other words, if you’re huffing and puffing, then you’re in the zone.

A version of this article first appeared on WebMD.com.

Vitamin D supplements do not prevent muscle symptoms in new statin users or affect the likelihood of discontinuing a statin due to muscle pain and discomfort, a substudy of the VITAL trial indicates.

Among more than 2,000 randomized participants, statin-associated muscle symptoms (SAMS) were reported by 31% assigned to vitamin D and 31% assigned to placebo.

copyright Joss/Fotolia.com

The two groups were equally likely to stop taking a statin due to muscle symptoms, at 13%.

No significant difference was observed in SAMS (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.80-1.18) or statin discontinuations (OR, 1.04; 95% CI, 0.80-1.35) after adjustment for baseline variables and other characteristics, namely age, sex, and African-American race, previously found to be associated with SAMS in VITAL.

“We actually thought when we started out that maybe we were going to show something, that maybe it was going to be that the people who got the vitamin D were least likely to have a problem with a statin than all those who didn’t get vitamin D, but that is not what we showed,” senior author Neil J. Stone, MD, Northwestern University, Chicago, told this news organization.

He noted that patients in the clinic with low levels of vitamin D often have muscle pain and discomfort and that previous unblinded studies suggested vitamin D might benefit patients with SAMS and reduce statin intolerance.

As previously reported, the double-blind VITAL trial showed no difference in the primary prevention of cardiovascular disease or cancer at 5 years among 25,871 middle-aged adults randomized to vitamin D3 at 2000 IU/d or placebo, regardless of their baseline vitamin D level.

Unlike previous studies showing a benefit with vitamin D on SAMS, importantly, VITAL participants were unaware of whether they were taking vitamin D or placebo and were not expecting any help with their muscle symptoms, first author Mark A. Hlatky, MD, Stanford (Calif.) University, pointed out in an interview.

As to how many statin users turn to the popular supplement for SAMS, he said that number couldn’t be pinned down, despite a lengthy search. “But I think it’s very common, because up to half of people stop taking their statins within a year and many of these do so because of statin-associated muscle symptoms, and we found it in about 30% of people who have them. I have them myself and was motivated to study it because I thought this was an interesting question.”

The results were published online in JAMA Cardiology.
 

SAMS by baseline 25-OHD

The substudy included 2,083 patients who initiated statin therapy after randomization and were surveyed in early 2016 about their statin use and muscle symptoms.

Two-thirds, or 1,397 patients, had 25-hydroxy vitamin D (25-OHD) measured at baseline, with 47% having levels < 30 ng/mL and 13% levels < 20 ng/mL.

Serum 25-OHD levels were virtually identical in the two treatment groups (mean, 30.4 ng/mL; median, 30.0 ng/mL). The frequency of SAMS did not differ between those assigned to vitamin D or placebo (28% vs. 31%).

The odds ratios for the association with vitamin D on SAMS were:

• 0.86 in all respondents with 25-OHD measured (95% CI, 0.69-1.09).
• 0.87 in those with levels ≥ 30 ng/mL (95% CI, 0.64-1.19).
• 0.85 with levels of 20-30 ng/mL (95% CI, 0.56-1.28).
• 0.93 with levels < 20 ng/mL (95% CI, 0.50-1.74).

The test for treatment effect modification by baseline serum 25-OHD level was not significant (P for interaction = .83).

In addition, the rate of muscle symptoms was similar between participants randomized to vitamin D and placebo when researchers used a cutpoint to define low 25-OHD of < 30 ng/mL (27% vs. 30%) or < 20 ng/mL (33% vs. 35%).

“We didn’t find any evidence at all that the people who came into the study with low levels of vitamin D did better with the supplement in this case,” Dr. Hlatky said. “So that wasn’t the reason we didn’t see anything.”

Critics may suggest the trial didn’t use a high enough dose of vitamin D, but both Dr. Hlatky and Dr. Stone say that’s unlikely to be a factor in the results because 2,000 IU/d is a substantial dose and well above the recommended adult daily dose of 600-800 IU.

They caution that the substudy wasn’t prespecified, was smaller than the parent trial, and did not have a protocol in place to detail SAMS. They also can’t rule out the possibility that vitamin D may have an effect in patients who have confirmed intolerance to multiple statins, especially after adjustment for the statin type and dose.

“If you’re taking vitamin D to keep from having statin-associated muscle symptoms, this very carefully done substudy with the various caveats doesn’t support that and that’s not something I would give my patients,” Dr. Stone said.

“The most important thing from a negative study is that it allows you to focus your attention on things that may be much more productive rather than assuming that just giving everybody vitamin D will take care of the statin issue,” he added. “Maybe the answer is going to be somewhere else, and there’ll be a lot of people I’m sure who will offer their advice as what the answer is but, I would argue, we want to see more studies to pin it down. So people can get some science behind what they do to try to reduce statin-associated muscle symptoms.”

Paul D. Thompson, MD, chief of cardiology emeritus at Hartford (Conn.) Hospital, and a SAMS expert who was not involved with the research, said, “This is a useful publication, and it’s smart in that it took advantage of a study that was already done.”

He acknowledged being skeptical of a beneficial effect of vitamin D supplementation on SAMS, because some previous data have been retracted, but said that potential treatments are best tested in patients with confirmed statin myalgia, as was the case in his team’s negative trial of CoQ10 supplementation.

That said, the present “study was able to at least give some of the best evidence so far that vitamin D doesn’t do anything to improve symptoms,” Dr. Thompson said. “So maybe it will cut down on so many vitamin D levels [being measured] and use of vitamin D when you don’t really need it.”

The study was sponsored by the Hyperlipidemia Research Fund at Northwestern University. The VITAL trial was supported by grants from the National Institutes of Health, and Quest Diagnostics performed the laboratory measurements at no additional costs. Dr. Hlatky reports no relevant financial relationships. Dr. Stone reports a grant from the Hyperlipidemia Research Fund at Northwestern and honorarium for educational activity for Knowledge to Practice. Dr. Thompson is on the executive committee for a study examining bempedoic acid in patients with statin-associated muscle symptoms.

A version of this article first appeared on Medscape.com.

Vitamin D supplements do not prevent muscle symptoms in new statin users or affect the likelihood of discontinuing a statin due to muscle pain and discomfort, a substudy of the VITAL trial indicates.

Among more than 2,000 randomized participants, statin-associated muscle symptoms (SAMS) were reported by 31% assigned to vitamin D and 31% assigned to placebo.

copyright Joss/Fotolia.com

The two groups were equally likely to stop taking a statin due to muscle symptoms, at 13%.

No significant difference was observed in SAMS (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.80-1.18) or statin discontinuations (OR, 1.04; 95% CI, 0.80-1.35) after adjustment for baseline variables and other characteristics, namely age, sex, and African-American race, previously found to be associated with SAMS in VITAL.

“We actually thought when we started out that maybe we were going to show something, that maybe it was going to be that the people who got the vitamin D were least likely to have a problem with a statin than all those who didn’t get vitamin D, but that is not what we showed,” senior author Neil J. Stone, MD, Northwestern University, Chicago, told this news organization.

He noted that patients in the clinic with low levels of vitamin D often have muscle pain and discomfort and that previous unblinded studies suggested vitamin D might benefit patients with SAMS and reduce statin intolerance.

As previously reported, the double-blind VITAL trial showed no difference in the primary prevention of cardiovascular disease or cancer at 5 years among 25,871 middle-aged adults randomized to vitamin D3 at 2000 IU/d or placebo, regardless of their baseline vitamin D level.

Unlike previous studies showing a benefit with vitamin D on SAMS, importantly, VITAL participants were unaware of whether they were taking vitamin D or placebo and were not expecting any help with their muscle symptoms, first author Mark A. Hlatky, MD, Stanford (Calif.) University, pointed out in an interview.

As to how many statin users turn to the popular supplement for SAMS, he said that number couldn’t be pinned down, despite a lengthy search. “But I think it’s very common, because up to half of people stop taking their statins within a year and many of these do so because of statin-associated muscle symptoms, and we found it in about 30% of people who have them. I have them myself and was motivated to study it because I thought this was an interesting question.”

The results were published online in JAMA Cardiology.
 

SAMS by baseline 25-OHD

The substudy included 2,083 patients who initiated statin therapy after randomization and were surveyed in early 2016 about their statin use and muscle symptoms.

Two-thirds, or 1,397 patients, had 25-hydroxy vitamin D (25-OHD) measured at baseline, with 47% having levels < 30 ng/mL and 13% levels < 20 ng/mL.

Serum 25-OHD levels were virtually identical in the two treatment groups (mean, 30.4 ng/mL; median, 30.0 ng/mL). The frequency of SAMS did not differ between those assigned to vitamin D or placebo (28% vs. 31%).

The odds ratios for the association with vitamin D on SAMS were:

• 0.86 in all respondents with 25-OHD measured (95% CI, 0.69-1.09).
• 0.87 in those with levels ≥ 30 ng/mL (95% CI, 0.64-1.19).
• 0.85 with levels of 20-30 ng/mL (95% CI, 0.56-1.28).
• 0.93 with levels < 20 ng/mL (95% CI, 0.50-1.74).

The test for treatment effect modification by baseline serum 25-OHD level was not significant (P for interaction = .83).

In addition, the rate of muscle symptoms was similar between participants randomized to vitamin D and placebo when researchers used a cutpoint to define low 25-OHD of < 30 ng/mL (27% vs. 30%) or < 20 ng/mL (33% vs. 35%).

“We didn’t find any evidence at all that the people who came into the study with low levels of vitamin D did better with the supplement in this case,” Dr. Hlatky said. “So that wasn’t the reason we didn’t see anything.”

Critics may suggest the trial didn’t use a high enough dose of vitamin D, but both Dr. Hlatky and Dr. Stone say that’s unlikely to be a factor in the results because 2,000 IU/d is a substantial dose and well above the recommended adult daily dose of 600-800 IU.

They caution that the substudy wasn’t prespecified, was smaller than the parent trial, and did not have a protocol in place to detail SAMS. They also can’t rule out the possibility that vitamin D may have an effect in patients who have confirmed intolerance to multiple statins, especially after adjustment for the statin type and dose.

“If you’re taking vitamin D to keep from having statin-associated muscle symptoms, this very carefully done substudy with the various caveats doesn’t support that and that’s not something I would give my patients,” Dr. Stone said.

“The most important thing from a negative study is that it allows you to focus your attention on things that may be much more productive rather than assuming that just giving everybody vitamin D will take care of the statin issue,” he added. “Maybe the answer is going to be somewhere else, and there’ll be a lot of people I’m sure who will offer their advice as what the answer is but, I would argue, we want to see more studies to pin it down. So people can get some science behind what they do to try to reduce statin-associated muscle symptoms.”

Paul D. Thompson, MD, chief of cardiology emeritus at Hartford (Conn.) Hospital, and a SAMS expert who was not involved with the research, said, “This is a useful publication, and it’s smart in that it took advantage of a study that was already done.”

He acknowledged being skeptical of a beneficial effect of vitamin D supplementation on SAMS, because some previous data have been retracted, but said that potential treatments are best tested in patients with confirmed statin myalgia, as was the case in his team’s negative trial of CoQ10 supplementation.

That said, the present “study was able to at least give some of the best evidence so far that vitamin D doesn’t do anything to improve symptoms,” Dr. Thompson said. “So maybe it will cut down on so many vitamin D levels [being measured] and use of vitamin D when you don’t really need it.”

The study was sponsored by the Hyperlipidemia Research Fund at Northwestern University. The VITAL trial was supported by grants from the National Institutes of Health, and Quest Diagnostics performed the laboratory measurements at no additional costs. Dr. Hlatky reports no relevant financial relationships. Dr. Stone reports a grant from the Hyperlipidemia Research Fund at Northwestern and honorarium for educational activity for Knowledge to Practice. Dr. Thompson is on the executive committee for a study examining bempedoic acid in patients with statin-associated muscle symptoms.

A version of this article first appeared on Medscape.com.

Vitamin D supplements do not prevent muscle symptoms in new statin users or affect the likelihood of discontinuing a statin due to muscle pain and discomfort, a substudy of the VITAL trial indicates.

Among more than 2,000 randomized participants, statin-associated muscle symptoms (SAMS) were reported by 31% assigned to vitamin D and 31% assigned to placebo.

copyright Joss/Fotolia.com

The two groups were equally likely to stop taking a statin due to muscle symptoms, at 13%.

No significant difference was observed in SAMS (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.80-1.18) or statin discontinuations (OR, 1.04; 95% CI, 0.80-1.35) after adjustment for baseline variables and other characteristics, namely age, sex, and African-American race, previously found to be associated with SAMS in VITAL.

“We actually thought when we started out that maybe we were going to show something, that maybe it was going to be that the people who got the vitamin D were least likely to have a problem with a statin than all those who didn’t get vitamin D, but that is not what we showed,” senior author Neil J. Stone, MD, Northwestern University, Chicago, told this news organization.

He noted that patients in the clinic with low levels of vitamin D often have muscle pain and discomfort and that previous unblinded studies suggested vitamin D might benefit patients with SAMS and reduce statin intolerance.

As previously reported, the double-blind VITAL trial showed no difference in the primary prevention of cardiovascular disease or cancer at 5 years among 25,871 middle-aged adults randomized to vitamin D3 at 2000 IU/d or placebo, regardless of their baseline vitamin D level.

Unlike previous studies showing a benefit with vitamin D on SAMS, importantly, VITAL participants were unaware of whether they were taking vitamin D or placebo and were not expecting any help with their muscle symptoms, first author Mark A. Hlatky, MD, Stanford (Calif.) University, pointed out in an interview.

As to how many statin users turn to the popular supplement for SAMS, he said that number couldn’t be pinned down, despite a lengthy search. “But I think it’s very common, because up to half of people stop taking their statins within a year and many of these do so because of statin-associated muscle symptoms, and we found it in about 30% of people who have them. I have them myself and was motivated to study it because I thought this was an interesting question.”

The results were published online in JAMA Cardiology.
 

SAMS by baseline 25-OHD

The substudy included 2,083 patients who initiated statin therapy after randomization and were surveyed in early 2016 about their statin use and muscle symptoms.

Two-thirds, or 1,397 patients, had 25-hydroxy vitamin D (25-OHD) measured at baseline, with 47% having levels < 30 ng/mL and 13% levels < 20 ng/mL.

Serum 25-OHD levels were virtually identical in the two treatment groups (mean, 30.4 ng/mL; median, 30.0 ng/mL). The frequency of SAMS did not differ between those assigned to vitamin D or placebo (28% vs. 31%).

The odds ratios for the association with vitamin D on SAMS were:

• 0.86 in all respondents with 25-OHD measured (95% CI, 0.69-1.09).
• 0.87 in those with levels ≥ 30 ng/mL (95% CI, 0.64-1.19).
• 0.85 with levels of 20-30 ng/mL (95% CI, 0.56-1.28).
• 0.93 with levels < 20 ng/mL (95% CI, 0.50-1.74).

The test for treatment effect modification by baseline serum 25-OHD level was not significant (P for interaction = .83).

In addition, the rate of muscle symptoms was similar between participants randomized to vitamin D and placebo when researchers used a cutpoint to define low 25-OHD of < 30 ng/mL (27% vs. 30%) or < 20 ng/mL (33% vs. 35%).

“We didn’t find any evidence at all that the people who came into the study with low levels of vitamin D did better with the supplement in this case,” Dr. Hlatky said. “So that wasn’t the reason we didn’t see anything.”

Critics may suggest the trial didn’t use a high enough dose of vitamin D, but both Dr. Hlatky and Dr. Stone say that’s unlikely to be a factor in the results because 2,000 IU/d is a substantial dose and well above the recommended adult daily dose of 600-800 IU.

They caution that the substudy wasn’t prespecified, was smaller than the parent trial, and did not have a protocol in place to detail SAMS. They also can’t rule out the possibility that vitamin D may have an effect in patients who have confirmed intolerance to multiple statins, especially after adjustment for the statin type and dose.

“If you’re taking vitamin D to keep from having statin-associated muscle symptoms, this very carefully done substudy with the various caveats doesn’t support that and that’s not something I would give my patients,” Dr. Stone said.

“The most important thing from a negative study is that it allows you to focus your attention on things that may be much more productive rather than assuming that just giving everybody vitamin D will take care of the statin issue,” he added. “Maybe the answer is going to be somewhere else, and there’ll be a lot of people I’m sure who will offer their advice as what the answer is but, I would argue, we want to see more studies to pin it down. So people can get some science behind what they do to try to reduce statin-associated muscle symptoms.”

Paul D. Thompson, MD, chief of cardiology emeritus at Hartford (Conn.) Hospital, and a SAMS expert who was not involved with the research, said, “This is a useful publication, and it’s smart in that it took advantage of a study that was already done.”

He acknowledged being skeptical of a beneficial effect of vitamin D supplementation on SAMS, because some previous data have been retracted, but said that potential treatments are best tested in patients with confirmed statin myalgia, as was the case in his team’s negative trial of CoQ10 supplementation.

That said, the present “study was able to at least give some of the best evidence so far that vitamin D doesn’t do anything to improve symptoms,” Dr. Thompson said. “So maybe it will cut down on so many vitamin D levels [being measured] and use of vitamin D when you don’t really need it.”

The study was sponsored by the Hyperlipidemia Research Fund at Northwestern University. The VITAL trial was supported by grants from the National Institutes of Health, and Quest Diagnostics performed the laboratory measurements at no additional costs. Dr. Hlatky reports no relevant financial relationships. Dr. Stone reports a grant from the Hyperlipidemia Research Fund at Northwestern and honorarium for educational activity for Knowledge to Practice. Dr. Thompson is on the executive committee for a study examining bempedoic acid in patients with statin-associated muscle symptoms.

A version of this article first appeared on Medscape.com.

PAU, France – Transgender patients on hormone therapy have an increased mortality risk and so must be closely monitored, especially in terms of cardiovascular health and oncology, reported Marie D’Assigny, MD, of the department of endocrinology, diabetes, and dietetics at Poitiers (France) University Hospital, at the Infogyn 2022 conference. Because transgender women (those assigned male at birth who have assumed a female gender identity) are at risk of breast cancer, they should also be recommended for breast cancer screening.

Transgender men and women, especially transgender women, “should be deemed high-risk cardiovascular patients, or even very high risk in some cases,” said Dr. D’Assigny. This means that they should be considered candidates for cholesterol-lowering medication earlier than their cisgender counterparts, and a target LDL cholesterol of less than 0.70 g/L (70 mg/dL) should be sought. Likewise, blood pressure must be strictly monitored, especially because it tends to rise when on hormone therapy.

Feminizing hormone therapy requires chemical castration with the use of anti-androgen drugs to achieve a blood testosterone level less than 0.5 ng/mL (1.73 nmol/L). Low-dose cyproterone acetate (< 25 to 50 mg/day) is usually used. Treatment is stopped if a patient undergoes an orchidectomy. For feminizing hormone therapy, administration of 17beta-estradiol transcutaneously (patch or gel) is recommended, because it is associated with a lower risk of thromboembolism than oral administration.

Masculinizing hormone therapy is based on administration of progestogens, then testosterone in the form of an injection (mostly testosterone enanthate via intramuscular injection every 10 days) or percutaneously (gel or patch). There are few contraindications, and treatment is generally well tolerated.
 

High mortality rate

A recent retrospective study highlighted the mortality and risk factors for death in transgender men and women receiving hormone therapy. More than 4,500 people, mostly male to female transgender women, were enrolled in this study, which was conducted over a 47-year period (1972-2018) at a specialist clinic at Amsterdam UMC.

Over the course of the study, the mortality rate in transgender men and women was twice that of the general population. The death rate was 10.8% in transgender women vs. 2.7% in transgender men, after a follow-up of 40,232 person-years and 17,285 person-years, respectively. In transgender women, mortality was nearly three times that of cisgender women in the general population.

Over the nearly 5 decades of study, there was no improvement in the mortality rate, even over the last 10 years when transgender issues started to be more recognized. The mortality trends are markedly distinct over the years from those observed in the cisgender population, and this is especially true for transgender women compared to transgender men. “Much is still to be done,” said Dr. D’Assigny.

According to the study, cause-specific mortality in transgender women was high for cardiovascular disease and lung cancer, possibly because of a higher smoking rate in this population. HIV-related disease and suicide remained very high in both transgender men and women.

People with gender dysphoria who do not receive treatment for gender reassignment have a suicide rate of 40%, reported François-Xavier Madec, MD, of Foch Hospital in Suresnes, France, at a previous presentation. For transgender men and women who receive care, this rate is lowered to 15%, which is still significantly higher than the rate of 1.6% observed in the general population.

“These causes of death don’t give any indication as to a specific effect of hormone treatment but show that monitoring and, if necessary, treatment of comorbidities and lifestyle-related factors are important in managing transgender patients,” said the study authors.

“Strengthening social acceptance and treating cardiovascular risk factors could also help to reduce mortality in transgender men and women,” they added.
 

Screening for osteoporosis

In addition to receiving cardiovascular risk factor assessment and monitoring, transgender men and women on hormone therapy should also undergo bone density testing “when risk factors for osteoporosis are present, especially in patients stopping hormone therapy after a gonadectomy,” said Dr. D’Assigny.

Calcium and vitamin D supplements are also recommended for all patients after a gonadectomy, especially in transgender men on testosterone. Osteoporosis screening is recommended for transgender men 10 years after starting treatment with testosterone, then every 10 years.

There is also the risk for breast cancer in transgender women, although the risk is lower than in cisgender women. This risk was highlighted in another study of more than 2,260 transgender women that was carried out by a team at Amsterdam UMC.

A total of 18 cases of breast cancer (15 invasive) were diagnosed after a median 18 years of hormone treatment. This represents an incidence of breast cancer that is 46 times higher than that expected in cisgender men of the same age but 3 times lower than in cisgender women.

The authors noted that “the risk of breast cancer in transgender women increases during a relatively short duration of hormone treatment,” going on to say that “these results suggest that breast cancer screening recommendations are relevant for transgender men and women on hormone therapy.”
 

Poorly attended screening

All of this means that transgender women older than age 50 years, as well as transgender men who have not had a mastectomy, should be offered a mammogram screening, taking into account the possible presence of implants in the former. Transgender women are also at risk for prostate cancer. Monitoring is personalized according to the individual risk of prostate disease, as it is for cisgender men.

There is no consensus on the monitoring of transgender men on hormone therapy for uterine cancer. Yet there is a risk. “Testosterone causes thinning of the endometrium, which may lead to dysplasia,” said Dr. D’Assigny. A physical examination once a year or a pelvic ultrasound scan every 2 years should form the basis of endometrial and ovarian appearance monitoring.

Transgender women are also at risk for prostate cancer. However, they are less likely to attend a prostate cancer screening test, said Dr. D’Assigny, which means “we need to raise awareness of their benefit in advance.” Vaginal swabs for transgender men and mammograms in transgender women “are resented, on both a physical and emotional level.” As a result, delays in diagnosis are common in transgender men and women.

Globally, access to care is still difficult for transgender patients because they don’t always receive appropriate gynecological monitoring, through fear of judgment or discrimination. Many transgender men and women are reluctant to see a gynecologist, even though they are at risk of gynecological cancers, as well as unwanted pregnancies in transgender men who have not undergone a hysterectomy.

In a demonstration of the collective desire to improve patient care for the transgender community, a literature review was recently published by a French team that analyzed gynecological monitoring methods in transgender patients. In September, the French National Authority for Health also issued a guidance memorandum on the transgender transition pathway, pending new recommendations scheduled for 2023.

A version of this article first appeared on Medscape.com.

This article was translated from the Medscape French edition.

PAU, France – Transgender patients on hormone therapy have an increased mortality risk and so must be closely monitored, especially in terms of cardiovascular health and oncology, reported Marie D’Assigny, MD, of the department of endocrinology, diabetes, and dietetics at Poitiers (France) University Hospital, at the Infogyn 2022 conference. Because transgender women (those assigned male at birth who have assumed a female gender identity) are at risk of breast cancer, they should also be recommended for breast cancer screening.

Transgender men and women, especially transgender women, “should be deemed high-risk cardiovascular patients, or even very high risk in some cases,” said Dr. D’Assigny. This means that they should be considered candidates for cholesterol-lowering medication earlier than their cisgender counterparts, and a target LDL cholesterol of less than 0.70 g/L (70 mg/dL) should be sought. Likewise, blood pressure must be strictly monitored, especially because it tends to rise when on hormone therapy.

Feminizing hormone therapy requires chemical castration with the use of anti-androgen drugs to achieve a blood testosterone level less than 0.5 ng/mL (1.73 nmol/L). Low-dose cyproterone acetate (< 25 to 50 mg/day) is usually used. Treatment is stopped if a patient undergoes an orchidectomy. For feminizing hormone therapy, administration of 17beta-estradiol transcutaneously (patch or gel) is recommended, because it is associated with a lower risk of thromboembolism than oral administration.

Masculinizing hormone therapy is based on administration of progestogens, then testosterone in the form of an injection (mostly testosterone enanthate via intramuscular injection every 10 days) or percutaneously (gel or patch). There are few contraindications, and treatment is generally well tolerated.
 

High mortality rate

A recent retrospective study highlighted the mortality and risk factors for death in transgender men and women receiving hormone therapy. More than 4,500 people, mostly male to female transgender women, were enrolled in this study, which was conducted over a 47-year period (1972-2018) at a specialist clinic at Amsterdam UMC.

Over the course of the study, the mortality rate in transgender men and women was twice that of the general population. The death rate was 10.8% in transgender women vs. 2.7% in transgender men, after a follow-up of 40,232 person-years and 17,285 person-years, respectively. In transgender women, mortality was nearly three times that of cisgender women in the general population.

Over the nearly 5 decades of study, there was no improvement in the mortality rate, even over the last 10 years when transgender issues started to be more recognized. The mortality trends are markedly distinct over the years from those observed in the cisgender population, and this is especially true for transgender women compared to transgender men. “Much is still to be done,” said Dr. D’Assigny.

According to the study, cause-specific mortality in transgender women was high for cardiovascular disease and lung cancer, possibly because of a higher smoking rate in this population. HIV-related disease and suicide remained very high in both transgender men and women.

People with gender dysphoria who do not receive treatment for gender reassignment have a suicide rate of 40%, reported François-Xavier Madec, MD, of Foch Hospital in Suresnes, France, at a previous presentation. For transgender men and women who receive care, this rate is lowered to 15%, which is still significantly higher than the rate of 1.6% observed in the general population.

“These causes of death don’t give any indication as to a specific effect of hormone treatment but show that monitoring and, if necessary, treatment of comorbidities and lifestyle-related factors are important in managing transgender patients,” said the study authors.

“Strengthening social acceptance and treating cardiovascular risk factors could also help to reduce mortality in transgender men and women,” they added.
 

Screening for osteoporosis

In addition to receiving cardiovascular risk factor assessment and monitoring, transgender men and women on hormone therapy should also undergo bone density testing “when risk factors for osteoporosis are present, especially in patients stopping hormone therapy after a gonadectomy,” said Dr. D’Assigny.

Calcium and vitamin D supplements are also recommended for all patients after a gonadectomy, especially in transgender men on testosterone. Osteoporosis screening is recommended for transgender men 10 years after starting treatment with testosterone, then every 10 years.

There is also the risk for breast cancer in transgender women, although the risk is lower than in cisgender women. This risk was highlighted in another study of more than 2,260 transgender women that was carried out by a team at Amsterdam UMC.

A total of 18 cases of breast cancer (15 invasive) were diagnosed after a median 18 years of hormone treatment. This represents an incidence of breast cancer that is 46 times higher than that expected in cisgender men of the same age but 3 times lower than in cisgender women.

The authors noted that “the risk of breast cancer in transgender women increases during a relatively short duration of hormone treatment,” going on to say that “these results suggest that breast cancer screening recommendations are relevant for transgender men and women on hormone therapy.”
 

Poorly attended screening

All of this means that transgender women older than age 50 years, as well as transgender men who have not had a mastectomy, should be offered a mammogram screening, taking into account the possible presence of implants in the former. Transgender women are also at risk for prostate cancer. Monitoring is personalized according to the individual risk of prostate disease, as it is for cisgender men.

There is no consensus on the monitoring of transgender men on hormone therapy for uterine cancer. Yet there is a risk. “Testosterone causes thinning of the endometrium, which may lead to dysplasia,” said Dr. D’Assigny. A physical examination once a year or a pelvic ultrasound scan every 2 years should form the basis of endometrial and ovarian appearance monitoring.

Transgender women are also at risk for prostate cancer. However, they are less likely to attend a prostate cancer screening test, said Dr. D’Assigny, which means “we need to raise awareness of their benefit in advance.” Vaginal swabs for transgender men and mammograms in transgender women “are resented, on both a physical and emotional level.” As a result, delays in diagnosis are common in transgender men and women.

Globally, access to care is still difficult for transgender patients because they don’t always receive appropriate gynecological monitoring, through fear of judgment or discrimination. Many transgender men and women are reluctant to see a gynecologist, even though they are at risk of gynecological cancers, as well as unwanted pregnancies in transgender men who have not undergone a hysterectomy.

In a demonstration of the collective desire to improve patient care for the transgender community, a literature review was recently published by a French team that analyzed gynecological monitoring methods in transgender patients. In September, the French National Authority for Health also issued a guidance memorandum on the transgender transition pathway, pending new recommendations scheduled for 2023.

A version of this article first appeared on Medscape.com.

This article was translated from the Medscape French edition.

PAU, France – Transgender patients on hormone therapy have an increased mortality risk and so must be closely monitored, especially in terms of cardiovascular health and oncology, reported Marie D’Assigny, MD, of the department of endocrinology, diabetes, and dietetics at Poitiers (France) University Hospital, at the Infogyn 2022 conference. Because transgender women (those assigned male at birth who have assumed a female gender identity) are at risk of breast cancer, they should also be recommended for breast cancer screening.

Transgender men and women, especially transgender women, “should be deemed high-risk cardiovascular patients, or even very high risk in some cases,” said Dr. D’Assigny. This means that they should be considered candidates for cholesterol-lowering medication earlier than their cisgender counterparts, and a target LDL cholesterol of less than 0.70 g/L (70 mg/dL) should be sought. Likewise, blood pressure must be strictly monitored, especially because it tends to rise when on hormone therapy.

Feminizing hormone therapy requires chemical castration with the use of anti-androgen drugs to achieve a blood testosterone level less than 0.5 ng/mL (1.73 nmol/L). Low-dose cyproterone acetate (< 25 to 50 mg/day) is usually used. Treatment is stopped if a patient undergoes an orchidectomy. For feminizing hormone therapy, administration of 17beta-estradiol transcutaneously (patch or gel) is recommended, because it is associated with a lower risk of thromboembolism than oral administration.

Masculinizing hormone therapy is based on administration of progestogens, then testosterone in the form of an injection (mostly testosterone enanthate via intramuscular injection every 10 days) or percutaneously (gel or patch). There are few contraindications, and treatment is generally well tolerated.
 

High mortality rate

A recent retrospective study highlighted the mortality and risk factors for death in transgender men and women receiving hormone therapy. More than 4,500 people, mostly male to female transgender women, were enrolled in this study, which was conducted over a 47-year period (1972-2018) at a specialist clinic at Amsterdam UMC.

Over the course of the study, the mortality rate in transgender men and women was twice that of the general population. The death rate was 10.8% in transgender women vs. 2.7% in transgender men, after a follow-up of 40,232 person-years and 17,285 person-years, respectively. In transgender women, mortality was nearly three times that of cisgender women in the general population.

Over the nearly 5 decades of study, there was no improvement in the mortality rate, even over the last 10 years when transgender issues started to be more recognized. The mortality trends are markedly distinct over the years from those observed in the cisgender population, and this is especially true for transgender women compared to transgender men. “Much is still to be done,” said Dr. D’Assigny.

According to the study, cause-specific mortality in transgender women was high for cardiovascular disease and lung cancer, possibly because of a higher smoking rate in this population. HIV-related disease and suicide remained very high in both transgender men and women.

People with gender dysphoria who do not receive treatment for gender reassignment have a suicide rate of 40%, reported François-Xavier Madec, MD, of Foch Hospital in Suresnes, France, at a previous presentation. For transgender men and women who receive care, this rate is lowered to 15%, which is still significantly higher than the rate of 1.6% observed in the general population.

“These causes of death don’t give any indication as to a specific effect of hormone treatment but show that monitoring and, if necessary, treatment of comorbidities and lifestyle-related factors are important in managing transgender patients,” said the study authors.

“Strengthening social acceptance and treating cardiovascular risk factors could also help to reduce mortality in transgender men and women,” they added.
 

Screening for osteoporosis

In addition to receiving cardiovascular risk factor assessment and monitoring, transgender men and women on hormone therapy should also undergo bone density testing “when risk factors for osteoporosis are present, especially in patients stopping hormone therapy after a gonadectomy,” said Dr. D’Assigny.

Calcium and vitamin D supplements are also recommended for all patients after a gonadectomy, especially in transgender men on testosterone. Osteoporosis screening is recommended for transgender men 10 years after starting treatment with testosterone, then every 10 years.

There is also the risk for breast cancer in transgender women, although the risk is lower than in cisgender women. This risk was highlighted in another study of more than 2,260 transgender women that was carried out by a team at Amsterdam UMC.

A total of 18 cases of breast cancer (15 invasive) were diagnosed after a median 18 years of hormone treatment. This represents an incidence of breast cancer that is 46 times higher than that expected in cisgender men of the same age but 3 times lower than in cisgender women.

The authors noted that “the risk of breast cancer in transgender women increases during a relatively short duration of hormone treatment,” going on to say that “these results suggest that breast cancer screening recommendations are relevant for transgender men and women on hormone therapy.”
 

Poorly attended screening

All of this means that transgender women older than age 50 years, as well as transgender men who have not had a mastectomy, should be offered a mammogram screening, taking into account the possible presence of implants in the former. Transgender women are also at risk for prostate cancer. Monitoring is personalized according to the individual risk of prostate disease, as it is for cisgender men.

There is no consensus on the monitoring of transgender men on hormone therapy for uterine cancer. Yet there is a risk. “Testosterone causes thinning of the endometrium, which may lead to dysplasia,” said Dr. D’Assigny. A physical examination once a year or a pelvic ultrasound scan every 2 years should form the basis of endometrial and ovarian appearance monitoring.

Transgender women are also at risk for prostate cancer. However, they are less likely to attend a prostate cancer screening test, said Dr. D’Assigny, which means “we need to raise awareness of their benefit in advance.” Vaginal swabs for transgender men and mammograms in transgender women “are resented, on both a physical and emotional level.” As a result, delays in diagnosis are common in transgender men and women.

Globally, access to care is still difficult for transgender patients because they don’t always receive appropriate gynecological monitoring, through fear of judgment or discrimination. Many transgender men and women are reluctant to see a gynecologist, even though they are at risk of gynecological cancers, as well as unwanted pregnancies in transgender men who have not undergone a hysterectomy.

In a demonstration of the collective desire to improve patient care for the transgender community, a literature review was recently published by a French team that analyzed gynecological monitoring methods in transgender patients. In September, the French National Authority for Health also issued a guidance memorandum on the transgender transition pathway, pending new recommendations scheduled for 2023.

A version of this article first appeared on Medscape.com.

This article was translated from the Medscape French edition.

One night, at the beginning of Thanksgiving week, my son called from his place across town. His car was having trouble starting, so I went to see what was up.

I got to his place to find his car wouldn’t start, even though the battery was only a few months old. I used my car to jump his, left him mine, and headed back. My plan was to leave it at our usual repair place and walk home.

Easier said than done.

I’d just gotten on the 101, the main loop freeway for the Phoenix metro area, when his car completely died. The lights flickered, the gauges stopped working, and then the engine cut out. Mercifully I was able to pull over into the right emergency lane as it did so. I was nowhere near an exit.

Not even the emergency flashers worked. It was dark. I was on a major freeway. I couldn’t make myself visible. Cars and trucks were whizzing by 2-3 feet to my left, and I was hoping they’d see me.

I called AAA and explained the situation. They were sending a tow truck, but it could take up to another 3 hours. I sent some quick texts to family to let them know what was up. I called the AZ highway patrol to let them know my predicament, in case they wanted to come put a flare or two behind me (they didn’t).

And then I settled in. Seatbelt on, staring at the road in front of me ... and had nothing to do.

When was the last time you had absolutely nothing to do?

It’s pretty rare these days. I mean, we all have breaks in the action, so we watch a cute animal video, or play a round of Wordle, or whatever.

But I had none of that. No books, iPad, or computer. Sure, I had my phone, but it was less than 50% charged with no way to charge it, and so I wanted to conserve that in case I needed it.

I don’t think I’ve ever had a moment like this since I began carrying a phone in 1998. There was, literally, nothing to do but wait. I couldn’t even try to nod off with the seat unadjustable and cars whizzing by.

So my mind wandered, and I thought. I turned over office cases. I went through year-end finances. I thought about my current predicament. I stared endlessly at the road ahead and cars passing me.

At some point I began to realize that I’m actually pretty lucky, and that nothing was nearly as bad as it had seemed earlier in the day. As the initial adrenaline rush drained out of me I calmed down and the things I’d been worrying about that afternoon seemed workable.

The tow truck pulled in front of me, ending my reverie. Mercifully, it had only taken them an hour. I was home 45 minutes later.

I was thankful to be home and I was thankful that nothing more serious had happened in a potentially bad situation.

And, somewhere in there, I was glad to be reminded that having nothing to do but think for a while can be a good thing.

In today’s world of endless screens and texts and calls and notifications, it’s easy to lose track of that.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

One night, at the beginning of Thanksgiving week, my son called from his place across town. His car was having trouble starting, so I went to see what was up.

I got to his place to find his car wouldn’t start, even though the battery was only a few months old. I used my car to jump his, left him mine, and headed back. My plan was to leave it at our usual repair place and walk home.

Easier said than done.

I’d just gotten on the 101, the main loop freeway for the Phoenix metro area, when his car completely died. The lights flickered, the gauges stopped working, and then the engine cut out. Mercifully I was able to pull over into the right emergency lane as it did so. I was nowhere near an exit.

Not even the emergency flashers worked. It was dark. I was on a major freeway. I couldn’t make myself visible. Cars and trucks were whizzing by 2-3 feet to my left, and I was hoping they’d see me.

I called AAA and explained the situation. They were sending a tow truck, but it could take up to another 3 hours. I sent some quick texts to family to let them know what was up. I called the AZ highway patrol to let them know my predicament, in case they wanted to come put a flare or two behind me (they didn’t).

And then I settled in. Seatbelt on, staring at the road in front of me ... and had nothing to do.

When was the last time you had absolutely nothing to do?

It’s pretty rare these days. I mean, we all have breaks in the action, so we watch a cute animal video, or play a round of Wordle, or whatever.

But I had none of that. No books, iPad, or computer. Sure, I had my phone, but it was less than 50% charged with no way to charge it, and so I wanted to conserve that in case I needed it.

I don’t think I’ve ever had a moment like this since I began carrying a phone in 1998. There was, literally, nothing to do but wait. I couldn’t even try to nod off with the seat unadjustable and cars whizzing by.

So my mind wandered, and I thought. I turned over office cases. I went through year-end finances. I thought about my current predicament. I stared endlessly at the road ahead and cars passing me.

At some point I began to realize that I’m actually pretty lucky, and that nothing was nearly as bad as it had seemed earlier in the day. As the initial adrenaline rush drained out of me I calmed down and the things I’d been worrying about that afternoon seemed workable.

The tow truck pulled in front of me, ending my reverie. Mercifully, it had only taken them an hour. I was home 45 minutes later.

I was thankful to be home and I was thankful that nothing more serious had happened in a potentially bad situation.

And, somewhere in there, I was glad to be reminded that having nothing to do but think for a while can be a good thing.

In today’s world of endless screens and texts and calls and notifications, it’s easy to lose track of that.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

One night, at the beginning of Thanksgiving week, my son called from his place across town. His car was having trouble starting, so I went to see what was up.

I got to his place to find his car wouldn’t start, even though the battery was only a few months old. I used my car to jump his, left him mine, and headed back. My plan was to leave it at our usual repair place and walk home.

Easier said than done.

I’d just gotten on the 101, the main loop freeway for the Phoenix metro area, when his car completely died. The lights flickered, the gauges stopped working, and then the engine cut out. Mercifully I was able to pull over into the right emergency lane as it did so. I was nowhere near an exit.

Not even the emergency flashers worked. It was dark. I was on a major freeway. I couldn’t make myself visible. Cars and trucks were whizzing by 2-3 feet to my left, and I was hoping they’d see me.

I called AAA and explained the situation. They were sending a tow truck, but it could take up to another 3 hours. I sent some quick texts to family to let them know what was up. I called the AZ highway patrol to let them know my predicament, in case they wanted to come put a flare or two behind me (they didn’t).

And then I settled in. Seatbelt on, staring at the road in front of me ... and had nothing to do.

When was the last time you had absolutely nothing to do?

It’s pretty rare these days. I mean, we all have breaks in the action, so we watch a cute animal video, or play a round of Wordle, or whatever.

But I had none of that. No books, iPad, or computer. Sure, I had my phone, but it was less than 50% charged with no way to charge it, and so I wanted to conserve that in case I needed it.

I don’t think I’ve ever had a moment like this since I began carrying a phone in 1998. There was, literally, nothing to do but wait. I couldn’t even try to nod off with the seat unadjustable and cars whizzing by.

So my mind wandered, and I thought. I turned over office cases. I went through year-end finances. I thought about my current predicament. I stared endlessly at the road ahead and cars passing me.

At some point I began to realize that I’m actually pretty lucky, and that nothing was nearly as bad as it had seemed earlier in the day. As the initial adrenaline rush drained out of me I calmed down and the things I’d been worrying about that afternoon seemed workable.

The tow truck pulled in front of me, ending my reverie. Mercifully, it had only taken them an hour. I was home 45 minutes later.

I was thankful to be home and I was thankful that nothing more serious had happened in a potentially bad situation.

And, somewhere in there, I was glad to be reminded that having nothing to do but think for a while can be a good thing.

In today’s world of endless screens and texts and calls and notifications, it’s easy to lose track of that.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.