Radiation has long been a part of treatment for localized prostate cancer. However, radiation and radiation-delivery modalities continue to evolve to decrease toxicity without sacrificing efficacy, expand the roles of these modalities, and enhance efficacy of other concomitantly delivered treatment modalities. The accompanying studies describe efforts to those effects.

            Hypofractionated delivery of radiation is now often considered preferred over conventionally fractionated radiation for localized prostate cancer to maintain efficacy while decreasing toxicity. To determine if the benefit of lower toxicity holds over time, Staffurth et al assessed patient-reported outcomes (PROs) in participants of the CHHiP trial where men were randomized to conventional radiation versus 2 alternative hypofraction schedules. At 5 years post-radiation, there were no significant differences amongst the 3 groups with respect to bowel bother, urinary bother, or sexual bother.

            Evidence is emerging that stereotactic body radiation therapy (SBRT) has benefits for oligometastatic disease; however, studies are emerging that support the hypothesis that radiation may enhance immunotherapy in many cancers in the metastatic setting. Kwan et al evaluated the effects of a single fraction of SBRT administered to 1 or 2 disease sites before the first and second doses of avelumab (a PD-L1 antibody) in patients with metastatic castrate-resistant prostate cancer (with prior exposure to at least one second-generation androgen receptor inhibitor). In this single arm phase II study, the disease control rate was 48%, overall response rate was 31%, median radiographic progression-free survival (rPFS) was 8.4 months, and median overall survival (OS) was 14.1 months in this heavily pretreated group of 31 participants. As immunotherapy has been considered efficacious in select groups of prostate cancer (such as tumors with microsatellite instability), this study supports ongoing and new efforts to evaluate how to enhance immunotherapy against prostate cancer.

            Radium-223 has been demonstrated to have efficacy in metastatic disease of the bone. Ongoing efforts to determine whether combined modality treatment in this setting may improve outcomes in metastatic disease, Maughn et al evaluated the combination of radium-223 and enzalutamide for safety and efficacy in a small and hypothesis-generating study 47 participants where 35 received enzalutamide plus radium-223 and 12 received enzlutamide alone. Of note, there were no increase in fractures (45 of the 47 participants received bone protective therapy, however), but there were no differences in the secondary endpoints of PSA-PFS, rPFS, or OS (primary endpoints of decline in bone metabolism markers were previously reported). This is a hypothesis generating study that supports the likely safety of this modality if bone protecting agents are utilized.

            The 3 studies summarized here represent the ongoing evolution of radiation or radiation-delivery modalities in localized and metastatic prostate cancer. It is encouraging to see the ongoing evaluate of PROs over time, as long-term quality of life in patients potentially cured of disease is of utmost importance. In addition, efforts to evaluate radiation or radium-223 in widely metastatic disease as part of combination therapy may reveal not only situations with modest benefits in efficacy, but more importantly, may reveal molecular insights into newer treatment strategies.

            Radiation has long been a part of treatment for localized prostate cancer. However, radiation and radiation-delivery modalities continue to evolve to decrease toxicity without sacrificing efficacy, expand the roles of these modalities, and enhance efficacy of other concomitantly delivered treatment modalities. The accompanying studies describe efforts to those effects.

            Hypofractionated delivery of radiation is now often considered preferred over conventionally fractionated radiation for localized prostate cancer to maintain efficacy while decreasing toxicity. To determine if the benefit of lower toxicity holds over time, Staffurth et al assessed patient-reported outcomes (PROs) in participants of the CHHiP trial where men were randomized to conventional radiation versus 2 alternative hypofraction schedules. At 5 years post-radiation, there were no significant differences amongst the 3 groups with respect to bowel bother, urinary bother, or sexual bother.

            Evidence is emerging that stereotactic body radiation therapy (SBRT) has benefits for oligometastatic disease; however, studies are emerging that support the hypothesis that radiation may enhance immunotherapy in many cancers in the metastatic setting. Kwan et al evaluated the effects of a single fraction of SBRT administered to 1 or 2 disease sites before the first and second doses of avelumab (a PD-L1 antibody) in patients with metastatic castrate-resistant prostate cancer (with prior exposure to at least one second-generation androgen receptor inhibitor). In this single arm phase II study, the disease control rate was 48%, overall response rate was 31%, median radiographic progression-free survival (rPFS) was 8.4 months, and median overall survival (OS) was 14.1 months in this heavily pretreated group of 31 participants. As immunotherapy has been considered efficacious in select groups of prostate cancer (such as tumors with microsatellite instability), this study supports ongoing and new efforts to evaluate how to enhance immunotherapy against prostate cancer.

            Radium-223 has been demonstrated to have efficacy in metastatic disease of the bone. Ongoing efforts to determine whether combined modality treatment in this setting may improve outcomes in metastatic disease, Maughn et al evaluated the combination of radium-223 and enzalutamide for safety and efficacy in a small and hypothesis-generating study 47 participants where 35 received enzalutamide plus radium-223 and 12 received enzlutamide alone. Of note, there were no increase in fractures (45 of the 47 participants received bone protective therapy, however), but there were no differences in the secondary endpoints of PSA-PFS, rPFS, or OS (primary endpoints of decline in bone metabolism markers were previously reported). This is a hypothesis generating study that supports the likely safety of this modality if bone protecting agents are utilized.

            The 3 studies summarized here represent the ongoing evolution of radiation or radiation-delivery modalities in localized and metastatic prostate cancer. It is encouraging to see the ongoing evaluate of PROs over time, as long-term quality of life in patients potentially cured of disease is of utmost importance. In addition, efforts to evaluate radiation or radium-223 in widely metastatic disease as part of combination therapy may reveal not only situations with modest benefits in efficacy, but more importantly, may reveal molecular insights into newer treatment strategies.

            Radiation has long been a part of treatment for localized prostate cancer. However, radiation and radiation-delivery modalities continue to evolve to decrease toxicity without sacrificing efficacy, expand the roles of these modalities, and enhance efficacy of other concomitantly delivered treatment modalities. The accompanying studies describe efforts to those effects.

            Hypofractionated delivery of radiation is now often considered preferred over conventionally fractionated radiation for localized prostate cancer to maintain efficacy while decreasing toxicity. To determine if the benefit of lower toxicity holds over time, Staffurth et al assessed patient-reported outcomes (PROs) in participants of the CHHiP trial where men were randomized to conventional radiation versus 2 alternative hypofraction schedules. At 5 years post-radiation, there were no significant differences amongst the 3 groups with respect to bowel bother, urinary bother, or sexual bother.

            Evidence is emerging that stereotactic body radiation therapy (SBRT) has benefits for oligometastatic disease; however, studies are emerging that support the hypothesis that radiation may enhance immunotherapy in many cancers in the metastatic setting. Kwan et al evaluated the effects of a single fraction of SBRT administered to 1 or 2 disease sites before the first and second doses of avelumab (a PD-L1 antibody) in patients with metastatic castrate-resistant prostate cancer (with prior exposure to at least one second-generation androgen receptor inhibitor). In this single arm phase II study, the disease control rate was 48%, overall response rate was 31%, median radiographic progression-free survival (rPFS) was 8.4 months, and median overall survival (OS) was 14.1 months in this heavily pretreated group of 31 participants. As immunotherapy has been considered efficacious in select groups of prostate cancer (such as tumors with microsatellite instability), this study supports ongoing and new efforts to evaluate how to enhance immunotherapy against prostate cancer.

            Radium-223 has been demonstrated to have efficacy in metastatic disease of the bone. Ongoing efforts to determine whether combined modality treatment in this setting may improve outcomes in metastatic disease, Maughn et al evaluated the combination of radium-223 and enzalutamide for safety and efficacy in a small and hypothesis-generating study 47 participants where 35 received enzalutamide plus radium-223 and 12 received enzlutamide alone. Of note, there were no increase in fractures (45 of the 47 participants received bone protective therapy, however), but there were no differences in the secondary endpoints of PSA-PFS, rPFS, or OS (primary endpoints of decline in bone metabolism markers were previously reported). This is a hypothesis generating study that supports the likely safety of this modality if bone protecting agents are utilized.

            The 3 studies summarized here represent the ongoing evolution of radiation or radiation-delivery modalities in localized and metastatic prostate cancer. It is encouraging to see the ongoing evaluate of PROs over time, as long-term quality of life in patients potentially cured of disease is of utmost importance. In addition, efforts to evaluate radiation or radium-223 in widely metastatic disease as part of combination therapy may reveal not only situations with modest benefits in efficacy, but more importantly, may reveal molecular insights into newer treatment strategies.

Treatment of patients with hepatocellular carcinoma (HCC) requires a multidisciplinary approach. This month we will review articles that analyze outcomes after liver resection compared to percutaneous ablation, prediction of immunotherapy efficacy based on observed treatment-related side effects, and the risk of subsequent malignancies in patients with HCC.

Xie et al. reported their retrospective review of outcomes of 67 adults with resectable caudate HCC within Milan criteria. Out of these, 46 underwent hepatic resection and 21 underwent percutaneous ablation. Overall survival at 1, 3, and 5 years was 97.6%, 83.6%, and 71.5%, respectively, for the hepatic resection patients, vs 89.4%, 58.5%, and 48.8%, respectively, for the percutaneous ablation patients (P = 0.032). Recurrence-free survival at these time points was 77.6%, 47.9%, and 42.6%, respectively, for the hepatic resection group, and 40.5%, 23.2%, and 15.4%, respectively, for the percutaneous ablation group (P = 0.010). The investigators concluded that HCC patients who underwent hepatic resection had significantly higher rates of recurrence-free and overall survival compared to those who underwent percutaneous ablation.

For those patients with unresectable HCC, systemic immune checkpoint inhibitor therapy is now part of the standard of care. Treatment-associated adverse events occur in over half of patients treated with immunotherapy. Pinato et al. reviewed the outcomes of a cohort of 406 adults with unresectable or advanced HCC who were receiving immune checkpoint inhibitor therapy while enrolled in clinical trials that were submitted to the Food and Drug Administration. the development of adverse events was associated with longer overall survival and progression-free survival rates compared to patients who did not develop treatment-related adverse events (16.7 months vs 11.2 months; 5.5 months vs 2.2 months, respectively).  The authors concluded that the development of treatment-related adverse events was significantly correlated with improve overall and progression-free survival in HCC patients treated with ICI monotherapy in clinical trials.

Finally, Kong et al. retrospectively looked at a cohort of 40,314 adult patients diagnosed with HCC between 2000 and 2014 in the SEER database, identifying the incidence of second primary cancers. Overall, the patients were followed for a median of 19 months following their HCC diagnosis. A total of 1,593 HCC patients (3.95%) developed secondary primary malignancies starting at 2 months after their initial HCC diagnosis. The 3-, 5-, and 10-year cumulative incidence of developing second primary malignancies were 2.35%, 3.12%, and 4.51%. The top five sites of the second primary malignancies were lung and bronchus, prostate, non-Hodgkin lymphoma, colon, and breast. The patients with poorer tumor-related characteristics such as larger tumor size, vascular invasion, positive AFP level, poorer tumor grade, and distant extension were associated with a decreased risk of developing second primary cancers, most probably because of their higher risk of dying from HCC. The authors developed a competing-risk nomogram for the purpose of improving guideline surveillance and further management of HCC survivors, concluding that HCC survivors should be monitored for evidence of secondary primary cancers.

Treatment of patients with hepatocellular carcinoma (HCC) requires a multidisciplinary approach. This month we will review articles that analyze outcomes after liver resection compared to percutaneous ablation, prediction of immunotherapy efficacy based on observed treatment-related side effects, and the risk of subsequent malignancies in patients with HCC.

Xie et al. reported their retrospective review of outcomes of 67 adults with resectable caudate HCC within Milan criteria. Out of these, 46 underwent hepatic resection and 21 underwent percutaneous ablation. Overall survival at 1, 3, and 5 years was 97.6%, 83.6%, and 71.5%, respectively, for the hepatic resection patients, vs 89.4%, 58.5%, and 48.8%, respectively, for the percutaneous ablation patients (P = 0.032). Recurrence-free survival at these time points was 77.6%, 47.9%, and 42.6%, respectively, for the hepatic resection group, and 40.5%, 23.2%, and 15.4%, respectively, for the percutaneous ablation group (P = 0.010). The investigators concluded that HCC patients who underwent hepatic resection had significantly higher rates of recurrence-free and overall survival compared to those who underwent percutaneous ablation.

For those patients with unresectable HCC, systemic immune checkpoint inhibitor therapy is now part of the standard of care. Treatment-associated adverse events occur in over half of patients treated with immunotherapy. Pinato et al. reviewed the outcomes of a cohort of 406 adults with unresectable or advanced HCC who were receiving immune checkpoint inhibitor therapy while enrolled in clinical trials that were submitted to the Food and Drug Administration. the development of adverse events was associated with longer overall survival and progression-free survival rates compared to patients who did not develop treatment-related adverse events (16.7 months vs 11.2 months; 5.5 months vs 2.2 months, respectively).  The authors concluded that the development of treatment-related adverse events was significantly correlated with improve overall and progression-free survival in HCC patients treated with ICI monotherapy in clinical trials.

Finally, Kong et al. retrospectively looked at a cohort of 40,314 adult patients diagnosed with HCC between 2000 and 2014 in the SEER database, identifying the incidence of second primary cancers. Overall, the patients were followed for a median of 19 months following their HCC diagnosis. A total of 1,593 HCC patients (3.95%) developed secondary primary malignancies starting at 2 months after their initial HCC diagnosis. The 3-, 5-, and 10-year cumulative incidence of developing second primary malignancies were 2.35%, 3.12%, and 4.51%. The top five sites of the second primary malignancies were lung and bronchus, prostate, non-Hodgkin lymphoma, colon, and breast. The patients with poorer tumor-related characteristics such as larger tumor size, vascular invasion, positive AFP level, poorer tumor grade, and distant extension were associated with a decreased risk of developing second primary cancers, most probably because of their higher risk of dying from HCC. The authors developed a competing-risk nomogram for the purpose of improving guideline surveillance and further management of HCC survivors, concluding that HCC survivors should be monitored for evidence of secondary primary cancers.

Treatment of patients with hepatocellular carcinoma (HCC) requires a multidisciplinary approach. This month we will review articles that analyze outcomes after liver resection compared to percutaneous ablation, prediction of immunotherapy efficacy based on observed treatment-related side effects, and the risk of subsequent malignancies in patients with HCC.

Xie et al. reported their retrospective review of outcomes of 67 adults with resectable caudate HCC within Milan criteria. Out of these, 46 underwent hepatic resection and 21 underwent percutaneous ablation. Overall survival at 1, 3, and 5 years was 97.6%, 83.6%, and 71.5%, respectively, for the hepatic resection patients, vs 89.4%, 58.5%, and 48.8%, respectively, for the percutaneous ablation patients (P = 0.032). Recurrence-free survival at these time points was 77.6%, 47.9%, and 42.6%, respectively, for the hepatic resection group, and 40.5%, 23.2%, and 15.4%, respectively, for the percutaneous ablation group (P = 0.010). The investigators concluded that HCC patients who underwent hepatic resection had significantly higher rates of recurrence-free and overall survival compared to those who underwent percutaneous ablation.

For those patients with unresectable HCC, systemic immune checkpoint inhibitor therapy is now part of the standard of care. Treatment-associated adverse events occur in over half of patients treated with immunotherapy. Pinato et al. reviewed the outcomes of a cohort of 406 adults with unresectable or advanced HCC who were receiving immune checkpoint inhibitor therapy while enrolled in clinical trials that were submitted to the Food and Drug Administration. the development of adverse events was associated with longer overall survival and progression-free survival rates compared to patients who did not develop treatment-related adverse events (16.7 months vs 11.2 months; 5.5 months vs 2.2 months, respectively).  The authors concluded that the development of treatment-related adverse events was significantly correlated with improve overall and progression-free survival in HCC patients treated with ICI monotherapy in clinical trials.

Finally, Kong et al. retrospectively looked at a cohort of 40,314 adult patients diagnosed with HCC between 2000 and 2014 in the SEER database, identifying the incidence of second primary cancers. Overall, the patients were followed for a median of 19 months following their HCC diagnosis. A total of 1,593 HCC patients (3.95%) developed secondary primary malignancies starting at 2 months after their initial HCC diagnosis. The 3-, 5-, and 10-year cumulative incidence of developing second primary malignancies were 2.35%, 3.12%, and 4.51%. The top five sites of the second primary malignancies were lung and bronchus, prostate, non-Hodgkin lymphoma, colon, and breast. The patients with poorer tumor-related characteristics such as larger tumor size, vascular invasion, positive AFP level, poorer tumor grade, and distant extension were associated with a decreased risk of developing second primary cancers, most probably because of their higher risk of dying from HCC. The authors developed a competing-risk nomogram for the purpose of improving guideline surveillance and further management of HCC survivors, concluding that HCC survivors should be monitored for evidence of secondary primary cancers.

Antipsychotics are not responsible for the increased COVID-related death rate among patients with serious mental illness (SMI), new research shows.

The significant increase in COVID-19 mortality that continues to be reported among those with schizophrenia and schizoaffective disorder “underscores the importance of protective interventions for this group, including priority vaccination,” study investigator Katlyn Nemani, MD, research assistant professor, department of psychiatry, New York University, told this news organization.

The study was published online September 22 in JAMA Psychiatry.
 

Threefold increase in death

Previous research has linked a diagnosis of a schizophrenia spectrum disorder, which includes schizophrenia and schizoaffective disorder, to an almost threefold increase in mortality among patients with COVID-19.

Some population-based research has also reported a link between antipsychotic medication use and increased risk for COVID-related mortality, but these studies did not take psychiatric diagnoses into account.

“This raised the question of whether the increased risk observed in this population is related to underlying psychiatric illness or its treatment,” said Dr. Nemani.

The retrospective cohort study included 464 adults (mean age, 53 years) who were diagnosed with COVID-19 between March 3, 2020, and Feb. 17, 2021, and who had previously been diagnosed with schizophrenia spectrum disorder or bipolar disorder. Of these, 42.2% were treated with an antipsychotic medication.

The primary endpoint was death within 60 days of COVID-19 diagnosis. Covariates included sociodemographic characteristics, such as patient-reported race and ethnicity, age, and insurance type, a psychiatric diagnosis, medical comorbidities, and smoking status.

Of the total, 41 patients (8.8%) died. The 60-day fatality rate was 13.7% among patients with a schizophrenia spectrum disorder (n = 182) and 5.7% among patients with bipolar disorder (n = 282).

Antipsychotic treatment was not significantly associated with mortality (odds ratio, 1.00; 95% confidence interval, 0.48-2.08; P = .99).

“This suggests that antipsychotic medication is unlikely to be responsible for the increased risk we’ve observed in this population, although this finding needs to be replicated,” said Dr. Nemani.
 

Surprise finding

A diagnosis of a schizophrenia spectrum disorder was associated with an almost threefold increased risk for mortality compared with bipolar disorder (OR, 2.88; 95% CI, 1.36-6.11; P = .006).

“This was a surprising finding,” said Dr. Nemani. “A possible explanation is differences in immune function associated with schizophrenia spectrum illness.”

She noted that there is evidence suggesting the immune system may play a role in the pathogenesis of schizophrenia, and research has shown that pneumonia and infection are among the leading causes of premature mortality in this population.

As well, several potential risk factors disproportionately affect people with serious mental illness, including an increase in the prevalence of medical comorbidities such as cardiovascular disease and diabetes, socioeconomic disadvantages, and barriers to accessing timely care. Prior studies have also found that people with SMI are less likely to receive preventive care interventions, including vaccination, said Dr. Nemani.

However, these factors are unlikely to fully account for the increased risk found in the study, she said.

“Our study population was limited to people who had received treatment within the NYU Langone Health System. We took a comprehensive list of sociodemographic and medical risk factors into account, and our research was conducted prior to the availability of COVID-19 vaccines,” she said.

Further research is necessary to understand what underlies the increase in susceptibility to severe infection among patients with schizophrenia and to identify interventions that may mitigate risk, said Dr. Nemani.

“This includes evaluating systems-level factors, such as access to preventive interventions and treatment, as well as investigating underlying immune mechanisms that may contribute to severe and fatal infection,” she said.

The researchers could not validate psychiatric diagnoses or capture deaths not documented in the electronic health record. In addition, the limited sample size precluded analysis of the use of individual antipsychotic medications, which may differ in their associated effects.

“It’s possible individual antipsychotic medications may be associated with harmful or protective effects,” said Dr. Nemani.

The authors have disclosed no relevant financial relationships.

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

Antipsychotics are not responsible for the increased COVID-related death rate among patients with serious mental illness (SMI), new research shows.

The significant increase in COVID-19 mortality that continues to be reported among those with schizophrenia and schizoaffective disorder “underscores the importance of protective interventions for this group, including priority vaccination,” study investigator Katlyn Nemani, MD, research assistant professor, department of psychiatry, New York University, told this news organization.

The study was published online September 22 in JAMA Psychiatry.
 

Threefold increase in death

Previous research has linked a diagnosis of a schizophrenia spectrum disorder, which includes schizophrenia and schizoaffective disorder, to an almost threefold increase in mortality among patients with COVID-19.

Some population-based research has also reported a link between antipsychotic medication use and increased risk for COVID-related mortality, but these studies did not take psychiatric diagnoses into account.

“This raised the question of whether the increased risk observed in this population is related to underlying psychiatric illness or its treatment,” said Dr. Nemani.

The retrospective cohort study included 464 adults (mean age, 53 years) who were diagnosed with COVID-19 between March 3, 2020, and Feb. 17, 2021, and who had previously been diagnosed with schizophrenia spectrum disorder or bipolar disorder. Of these, 42.2% were treated with an antipsychotic medication.

The primary endpoint was death within 60 days of COVID-19 diagnosis. Covariates included sociodemographic characteristics, such as patient-reported race and ethnicity, age, and insurance type, a psychiatric diagnosis, medical comorbidities, and smoking status.

Of the total, 41 patients (8.8%) died. The 60-day fatality rate was 13.7% among patients with a schizophrenia spectrum disorder (n = 182) and 5.7% among patients with bipolar disorder (n = 282).

Antipsychotic treatment was not significantly associated with mortality (odds ratio, 1.00; 95% confidence interval, 0.48-2.08; P = .99).

“This suggests that antipsychotic medication is unlikely to be responsible for the increased risk we’ve observed in this population, although this finding needs to be replicated,” said Dr. Nemani.
 

Surprise finding

A diagnosis of a schizophrenia spectrum disorder was associated with an almost threefold increased risk for mortality compared with bipolar disorder (OR, 2.88; 95% CI, 1.36-6.11; P = .006).

“This was a surprising finding,” said Dr. Nemani. “A possible explanation is differences in immune function associated with schizophrenia spectrum illness.”

She noted that there is evidence suggesting the immune system may play a role in the pathogenesis of schizophrenia, and research has shown that pneumonia and infection are among the leading causes of premature mortality in this population.

As well, several potential risk factors disproportionately affect people with serious mental illness, including an increase in the prevalence of medical comorbidities such as cardiovascular disease and diabetes, socioeconomic disadvantages, and barriers to accessing timely care. Prior studies have also found that people with SMI are less likely to receive preventive care interventions, including vaccination, said Dr. Nemani.

However, these factors are unlikely to fully account for the increased risk found in the study, she said.

“Our study population was limited to people who had received treatment within the NYU Langone Health System. We took a comprehensive list of sociodemographic and medical risk factors into account, and our research was conducted prior to the availability of COVID-19 vaccines,” she said.

Further research is necessary to understand what underlies the increase in susceptibility to severe infection among patients with schizophrenia and to identify interventions that may mitigate risk, said Dr. Nemani.

“This includes evaluating systems-level factors, such as access to preventive interventions and treatment, as well as investigating underlying immune mechanisms that may contribute to severe and fatal infection,” she said.

The researchers could not validate psychiatric diagnoses or capture deaths not documented in the electronic health record. In addition, the limited sample size precluded analysis of the use of individual antipsychotic medications, which may differ in their associated effects.

“It’s possible individual antipsychotic medications may be associated with harmful or protective effects,” said Dr. Nemani.

The authors have disclosed no relevant financial relationships.

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

Antipsychotics are not responsible for the increased COVID-related death rate among patients with serious mental illness (SMI), new research shows.

The significant increase in COVID-19 mortality that continues to be reported among those with schizophrenia and schizoaffective disorder “underscores the importance of protective interventions for this group, including priority vaccination,” study investigator Katlyn Nemani, MD, research assistant professor, department of psychiatry, New York University, told this news organization.

The study was published online September 22 in JAMA Psychiatry.
 

Threefold increase in death

Previous research has linked a diagnosis of a schizophrenia spectrum disorder, which includes schizophrenia and schizoaffective disorder, to an almost threefold increase in mortality among patients with COVID-19.

Some population-based research has also reported a link between antipsychotic medication use and increased risk for COVID-related mortality, but these studies did not take psychiatric diagnoses into account.

“This raised the question of whether the increased risk observed in this population is related to underlying psychiatric illness or its treatment,” said Dr. Nemani.

The retrospective cohort study included 464 adults (mean age, 53 years) who were diagnosed with COVID-19 between March 3, 2020, and Feb. 17, 2021, and who had previously been diagnosed with schizophrenia spectrum disorder or bipolar disorder. Of these, 42.2% were treated with an antipsychotic medication.

The primary endpoint was death within 60 days of COVID-19 diagnosis. Covariates included sociodemographic characteristics, such as patient-reported race and ethnicity, age, and insurance type, a psychiatric diagnosis, medical comorbidities, and smoking status.

Of the total, 41 patients (8.8%) died. The 60-day fatality rate was 13.7% among patients with a schizophrenia spectrum disorder (n = 182) and 5.7% among patients with bipolar disorder (n = 282).

Antipsychotic treatment was not significantly associated with mortality (odds ratio, 1.00; 95% confidence interval, 0.48-2.08; P = .99).

“This suggests that antipsychotic medication is unlikely to be responsible for the increased risk we’ve observed in this population, although this finding needs to be replicated,” said Dr. Nemani.
 

Surprise finding

A diagnosis of a schizophrenia spectrum disorder was associated with an almost threefold increased risk for mortality compared with bipolar disorder (OR, 2.88; 95% CI, 1.36-6.11; P = .006).

“This was a surprising finding,” said Dr. Nemani. “A possible explanation is differences in immune function associated with schizophrenia spectrum illness.”

She noted that there is evidence suggesting the immune system may play a role in the pathogenesis of schizophrenia, and research has shown that pneumonia and infection are among the leading causes of premature mortality in this population.

As well, several potential risk factors disproportionately affect people with serious mental illness, including an increase in the prevalence of medical comorbidities such as cardiovascular disease and diabetes, socioeconomic disadvantages, and barriers to accessing timely care. Prior studies have also found that people with SMI are less likely to receive preventive care interventions, including vaccination, said Dr. Nemani.

However, these factors are unlikely to fully account for the increased risk found in the study, she said.

“Our study population was limited to people who had received treatment within the NYU Langone Health System. We took a comprehensive list of sociodemographic and medical risk factors into account, and our research was conducted prior to the availability of COVID-19 vaccines,” she said.

Further research is necessary to understand what underlies the increase in susceptibility to severe infection among patients with schizophrenia and to identify interventions that may mitigate risk, said Dr. Nemani.

“This includes evaluating systems-level factors, such as access to preventive interventions and treatment, as well as investigating underlying immune mechanisms that may contribute to severe and fatal infection,” she said.

The researchers could not validate psychiatric diagnoses or capture deaths not documented in the electronic health record. In addition, the limited sample size precluded analysis of the use of individual antipsychotic medications, which may differ in their associated effects.

“It’s possible individual antipsychotic medications may be associated with harmful or protective effects,” said Dr. Nemani.

The authors have disclosed no relevant financial relationships.

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

The patient is probably presenting with relapsing-remitting multiple sclerosis (RRMS). MS is characterized by symptomatic episodes that are heralded by symptoms of central nervous system involvement. These attacks last longer than 24 hours and may occur months or years apart and affect different anatomic locations. Consistent with other autoimmune conditions, MS is more common in women. Patients are usually diagnosed between the ages of 20 and 49 years. The condition presents differently from patient to patient; some experience cognitive changes or visual symptoms, while others may have numbness, ataxia, clumsiness, hemiparesis, paraparesis, depression, or seizures. Symptoms can also include fatigue, impaired mobility, mood diagnosed changes, elimination dysfunction, and pain.

Of the four disease courses identified in MS, the most common is RRMS, characterized by a cycle of relapse and remission. In the initial stages, RRMS is characterized largely by an inflammatory pathology which, over time, becomes largely neurodegenerative. Most cases of RRMS evolve to secondary progressive MS after about 15 years. Early in the spectrum of demyelinating disease is clinically isolated syndrome (CIS), defined by a single episode of neurologic symptoms and MRI showing more than two classic lesions seen in MS. CIS patients subsequently will present with a second episode or relapse, at which point the diagnosis of RRMS is usually confirmed.

MS is diagnosed on the basis of clinical findings, exclusion of mimickers, and supporting evidence from the workup, namely MRI of the brain and spinal cord as well as cerebrospinal fluid examination. From a clinical perspective, presentation must align with the constellation of neurologic deficits seen in MS. Typically, the duration of deficit is days to weeks, as seen in the present case. While MRI alone cannot be used to diagnose MS, imaging may confirm diagnosis and offer value in monitoring disease progression in the brain and spinal cord. New lesions on MRI usually occur with relapses in RRMS. 

Treatment of MS encompasses immunomodulatory therapy to address the underlying immune disorder together with therapies to relieve symptoms. In general, disease-modifying therapy (DMT) should be considered for patients who have experienced a single demyelinating event and exhibit two or more brain lesions on MRI testing. This recommendation holds true even for patients with CIS or those who have experienced their first clinical event and have MRI features consistent with MS, so long as all other conditions in the differential are ruled out. Pivotal trials support the early initiation of DMT with CIS to delay disability.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

The patient is probably presenting with relapsing-remitting multiple sclerosis (RRMS). MS is characterized by symptomatic episodes that are heralded by symptoms of central nervous system involvement. These attacks last longer than 24 hours and may occur months or years apart and affect different anatomic locations. Consistent with other autoimmune conditions, MS is more common in women. Patients are usually diagnosed between the ages of 20 and 49 years. The condition presents differently from patient to patient; some experience cognitive changes or visual symptoms, while others may have numbness, ataxia, clumsiness, hemiparesis, paraparesis, depression, or seizures. Symptoms can also include fatigue, impaired mobility, mood diagnosed changes, elimination dysfunction, and pain.

Of the four disease courses identified in MS, the most common is RRMS, characterized by a cycle of relapse and remission. In the initial stages, RRMS is characterized largely by an inflammatory pathology which, over time, becomes largely neurodegenerative. Most cases of RRMS evolve to secondary progressive MS after about 15 years. Early in the spectrum of demyelinating disease is clinically isolated syndrome (CIS), defined by a single episode of neurologic symptoms and MRI showing more than two classic lesions seen in MS. CIS patients subsequently will present with a second episode or relapse, at which point the diagnosis of RRMS is usually confirmed.

MS is diagnosed on the basis of clinical findings, exclusion of mimickers, and supporting evidence from the workup, namely MRI of the brain and spinal cord as well as cerebrospinal fluid examination. From a clinical perspective, presentation must align with the constellation of neurologic deficits seen in MS. Typically, the duration of deficit is days to weeks, as seen in the present case. While MRI alone cannot be used to diagnose MS, imaging may confirm diagnosis and offer value in monitoring disease progression in the brain and spinal cord. New lesions on MRI usually occur with relapses in RRMS. 

Treatment of MS encompasses immunomodulatory therapy to address the underlying immune disorder together with therapies to relieve symptoms. In general, disease-modifying therapy (DMT) should be considered for patients who have experienced a single demyelinating event and exhibit two or more brain lesions on MRI testing. This recommendation holds true even for patients with CIS or those who have experienced their first clinical event and have MRI features consistent with MS, so long as all other conditions in the differential are ruled out. Pivotal trials support the early initiation of DMT with CIS to delay disability.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

The patient is probably presenting with relapsing-remitting multiple sclerosis (RRMS). MS is characterized by symptomatic episodes that are heralded by symptoms of central nervous system involvement. These attacks last longer than 24 hours and may occur months or years apart and affect different anatomic locations. Consistent with other autoimmune conditions, MS is more common in women. Patients are usually diagnosed between the ages of 20 and 49 years. The condition presents differently from patient to patient; some experience cognitive changes or visual symptoms, while others may have numbness, ataxia, clumsiness, hemiparesis, paraparesis, depression, or seizures. Symptoms can also include fatigue, impaired mobility, mood diagnosed changes, elimination dysfunction, and pain.

Of the four disease courses identified in MS, the most common is RRMS, characterized by a cycle of relapse and remission. In the initial stages, RRMS is characterized largely by an inflammatory pathology which, over time, becomes largely neurodegenerative. Most cases of RRMS evolve to secondary progressive MS after about 15 years. Early in the spectrum of demyelinating disease is clinically isolated syndrome (CIS), defined by a single episode of neurologic symptoms and MRI showing more than two classic lesions seen in MS. CIS patients subsequently will present with a second episode or relapse, at which point the diagnosis of RRMS is usually confirmed.

MS is diagnosed on the basis of clinical findings, exclusion of mimickers, and supporting evidence from the workup, namely MRI of the brain and spinal cord as well as cerebrospinal fluid examination. From a clinical perspective, presentation must align with the constellation of neurologic deficits seen in MS. Typically, the duration of deficit is days to weeks, as seen in the present case. While MRI alone cannot be used to diagnose MS, imaging may confirm diagnosis and offer value in monitoring disease progression in the brain and spinal cord. New lesions on MRI usually occur with relapses in RRMS. 

Treatment of MS encompasses immunomodulatory therapy to address the underlying immune disorder together with therapies to relieve symptoms. In general, disease-modifying therapy (DMT) should be considered for patients who have experienced a single demyelinating event and exhibit two or more brain lesions on MRI testing. This recommendation holds true even for patients with CIS or those who have experienced their first clinical event and have MRI features consistent with MS, so long as all other conditions in the differential are ruled out. Pivotal trials support the early initiation of DMT with CIS to delay disability.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

Novel food for thought

When you were growing up, your parents probably told you to brush your teeth before you went to bed, warned you not to run with the scissors or play with matches, and punished you whenever you used the neighbor children to play Schrödinger’s cat.

World Wildlife/StockSnap

They did those things for your own good, of course, and now the nation’s mother – the Centers for Disease Control and Prevention – is doing the same by warning us about novel outbreak–associated foods. As in, “Put down that novel outbreak–associated food! You don’t know where it’s been!”

Seriously, you don’t know where it’s been. CDC investigators identified 28 novel foods that were linked to 36 foodborne-disease outbreaks that occurred during 2007-2016, including moringa leaf (herb/spice), tempeh (grain), frog, sprouted nut butter, and skate.

The novel foods implicated in these outbreaks were more likely to be imported, compared with 14,216 outbreaks that occurred from 1973 to 2016, and about half didn’t require refrigeration. Two-thirds did not need to be cooked after purchase. Another thing your parents wouldn’t like: Some can’t be washed, like sheep milk, sugar cane, or the aforementioned nut butter.

We wanted to get a food expert to comment on these novel foods, but our editor said that the assistant manager of our local Burger King wasn’t expert enough, so we’ve commandeered someone else’s expert. Cynthia Sears, MD, of Johns Hopkins University in Baltimore, told Today.com all about the dangers of frogs: “Essentially all amphibians are contaminated, often with salmonella. Eating any amphibian that is not thoroughly cooked is a risk.”

Be sure to cook your amphibians before you eat them. Advice that your parents would be proud to share.
 

Dieters should stay away from diet drinks

When a drink is labeled “diet” many assume that the calorie-free beverage is the best choice. However, one of the largest studies to date on artificial sweeteners is out to set the record straight.

American Heart Association

Artificial sweeteners, or nonnutritive sweeteners (NNS), are used in most if not all diet products to give the illusion of sweetness without the caloric guilt. Some studies say they help with weight loss for that very reason, but others say they can contribute to weight gain. So which is it?

Researchers at the University of Southern California sought to add some clarity to the research already out there.

They looked at an even-gendered split of 74 participants who drank 300 mL of drinks sweetened with NNS, table sugar, or water. The researchers then used functional MRI to see how parts of the brain responsible for appetite and cravings responded to images of high-calorie foods. They also looked at glucose, insulin, and other metabolic hormone levels, as well as how much food the participants ate at their free buffet. (In the participants’ defense, who can say no to a free buffet?)

The researchers made some interesting observations:

• Women who drank the NNS drink ate more than did the table-sugar group, but all men ate the same.
• Images of those calorie-packed goodies increased cravings and appetite for obese men and women in the NNS group, compared with the table-sugar group.
• For all participants who drank the NNS drink, there was a decrease in the hormone that tells the body it’s full.

“By studying different groups we were able to show that females and people with obesity may be more sensitive to artificial sweeteners. For these groups, drinking artificially sweetened drinks may trick the brain into feeling hungry, which may in turn result in more calories being consumed,” Kathleen Page, MD, the study’s corresponding author, said in a separate statement.

Today’s lesson? Don’t believe every label you read.
 

Instagram vegetables and the triumph of peer pressure

You and your family are sitting down for dinner. You’ve taken the time to prepare a healthy, nutritious meal. Vegetables, rice, seafood – all the right things. But the children around you refuse to partake. What can you do? Why, show them a highly liked photo of broccoli on Instagram!

Teresa Burton/IMNG Medical Media

In reality, kids will probably never like to eat their vegetables, but according to a study published in Appetite, viewing highly liked images on social media can compel adults to eat theirs.

The investigators recruited a group of 169 adults aged 18-28 (average age, 21) and showed them a series of mock Instagram posts of all sorts of food, everything from Brussels sprouts to chocolate cake, as well as nonfood images to act as a baseline. The images had a varying amount of likes. After viewing the images, study participants were offered a snack buffet consisting of grapes and cookies.

The results were a triumph of peer pressure. Those who viewed highly liked images of nutritious foods ate a significantly larger proportion of grapes, compared with those who saw highly liked images of unhealthy food or nonfood.

The authors cautioned that more research is needed, but they said that they’re onto something in the eternal struggle of getting people to eat better. If Mikey liked it, maybe you should, too. Just as long as you don’t try to encourage the eating of peas. That is a dark road none should take, and no one should ever be subjected to that cursed food.
 

It’s nice to share … hypertension?

You may have heard that, over time, you begin to resemble your spouse. You may have also heard that, as time goes by, your pet might start to resemble you, but that is a story for another time.

sabelskaya/iStock/Getty Images Plus

A lot of the time, it’s human nature that people partner with someone who is similar to them in physical and environmental status. If you like to go jogging at 5 a.m., you might want a spouse who does the same. A study done using data from couples in Japan and the Netherlands found that couples who had the same lifestyle had similar levels of blood pressure, cholesterol, and triglycerides. They also had similar illnesses such as hypertension and diabetes.

It’s important to note that many of the couples were not very genetically similar but had similar lifestyles. Encourage your partner to have a healthier lifestyle, so you can live on for many years to come!

Novel food for thought

When you were growing up, your parents probably told you to brush your teeth before you went to bed, warned you not to run with the scissors or play with matches, and punished you whenever you used the neighbor children to play Schrödinger’s cat.

World Wildlife/StockSnap

They did those things for your own good, of course, and now the nation’s mother – the Centers for Disease Control and Prevention – is doing the same by warning us about novel outbreak–associated foods. As in, “Put down that novel outbreak–associated food! You don’t know where it’s been!”

Seriously, you don’t know where it’s been. CDC investigators identified 28 novel foods that were linked to 36 foodborne-disease outbreaks that occurred during 2007-2016, including moringa leaf (herb/spice), tempeh (grain), frog, sprouted nut butter, and skate.

The novel foods implicated in these outbreaks were more likely to be imported, compared with 14,216 outbreaks that occurred from 1973 to 2016, and about half didn’t require refrigeration. Two-thirds did not need to be cooked after purchase. Another thing your parents wouldn’t like: Some can’t be washed, like sheep milk, sugar cane, or the aforementioned nut butter.

We wanted to get a food expert to comment on these novel foods, but our editor said that the assistant manager of our local Burger King wasn’t expert enough, so we’ve commandeered someone else’s expert. Cynthia Sears, MD, of Johns Hopkins University in Baltimore, told Today.com all about the dangers of frogs: “Essentially all amphibians are contaminated, often with salmonella. Eating any amphibian that is not thoroughly cooked is a risk.”

Be sure to cook your amphibians before you eat them. Advice that your parents would be proud to share.
 

Dieters should stay away from diet drinks

When a drink is labeled “diet” many assume that the calorie-free beverage is the best choice. However, one of the largest studies to date on artificial sweeteners is out to set the record straight.

American Heart Association

Artificial sweeteners, or nonnutritive sweeteners (NNS), are used in most if not all diet products to give the illusion of sweetness without the caloric guilt. Some studies say they help with weight loss for that very reason, but others say they can contribute to weight gain. So which is it?

Researchers at the University of Southern California sought to add some clarity to the research already out there.

They looked at an even-gendered split of 74 participants who drank 300 mL of drinks sweetened with NNS, table sugar, or water. The researchers then used functional MRI to see how parts of the brain responsible for appetite and cravings responded to images of high-calorie foods. They also looked at glucose, insulin, and other metabolic hormone levels, as well as how much food the participants ate at their free buffet. (In the participants’ defense, who can say no to a free buffet?)

The researchers made some interesting observations:

• Women who drank the NNS drink ate more than did the table-sugar group, but all men ate the same.
• Images of those calorie-packed goodies increased cravings and appetite for obese men and women in the NNS group, compared with the table-sugar group.
• For all participants who drank the NNS drink, there was a decrease in the hormone that tells the body it’s full.

“By studying different groups we were able to show that females and people with obesity may be more sensitive to artificial sweeteners. For these groups, drinking artificially sweetened drinks may trick the brain into feeling hungry, which may in turn result in more calories being consumed,” Kathleen Page, MD, the study’s corresponding author, said in a separate statement.

Today’s lesson? Don’t believe every label you read.
 

Instagram vegetables and the triumph of peer pressure

You and your family are sitting down for dinner. You’ve taken the time to prepare a healthy, nutritious meal. Vegetables, rice, seafood – all the right things. But the children around you refuse to partake. What can you do? Why, show them a highly liked photo of broccoli on Instagram!

Teresa Burton/IMNG Medical Media

In reality, kids will probably never like to eat their vegetables, but according to a study published in Appetite, viewing highly liked images on social media can compel adults to eat theirs.

The investigators recruited a group of 169 adults aged 18-28 (average age, 21) and showed them a series of mock Instagram posts of all sorts of food, everything from Brussels sprouts to chocolate cake, as well as nonfood images to act as a baseline. The images had a varying amount of likes. After viewing the images, study participants were offered a snack buffet consisting of grapes and cookies.

The results were a triumph of peer pressure. Those who viewed highly liked images of nutritious foods ate a significantly larger proportion of grapes, compared with those who saw highly liked images of unhealthy food or nonfood.

The authors cautioned that more research is needed, but they said that they’re onto something in the eternal struggle of getting people to eat better. If Mikey liked it, maybe you should, too. Just as long as you don’t try to encourage the eating of peas. That is a dark road none should take, and no one should ever be subjected to that cursed food.
 

It’s nice to share … hypertension?

You may have heard that, over time, you begin to resemble your spouse. You may have also heard that, as time goes by, your pet might start to resemble you, but that is a story for another time.

sabelskaya/iStock/Getty Images Plus

A lot of the time, it’s human nature that people partner with someone who is similar to them in physical and environmental status. If you like to go jogging at 5 a.m., you might want a spouse who does the same. A study done using data from couples in Japan and the Netherlands found that couples who had the same lifestyle had similar levels of blood pressure, cholesterol, and triglycerides. They also had similar illnesses such as hypertension and diabetes.

It’s important to note that many of the couples were not very genetically similar but had similar lifestyles. Encourage your partner to have a healthier lifestyle, so you can live on for many years to come!

Novel food for thought

When you were growing up, your parents probably told you to brush your teeth before you went to bed, warned you not to run with the scissors or play with matches, and punished you whenever you used the neighbor children to play Schrödinger’s cat.

World Wildlife/StockSnap

They did those things for your own good, of course, and now the nation’s mother – the Centers for Disease Control and Prevention – is doing the same by warning us about novel outbreak–associated foods. As in, “Put down that novel outbreak–associated food! You don’t know where it’s been!”

Seriously, you don’t know where it’s been. CDC investigators identified 28 novel foods that were linked to 36 foodborne-disease outbreaks that occurred during 2007-2016, including moringa leaf (herb/spice), tempeh (grain), frog, sprouted nut butter, and skate.

The novel foods implicated in these outbreaks were more likely to be imported, compared with 14,216 outbreaks that occurred from 1973 to 2016, and about half didn’t require refrigeration. Two-thirds did not need to be cooked after purchase. Another thing your parents wouldn’t like: Some can’t be washed, like sheep milk, sugar cane, or the aforementioned nut butter.

We wanted to get a food expert to comment on these novel foods, but our editor said that the assistant manager of our local Burger King wasn’t expert enough, so we’ve commandeered someone else’s expert. Cynthia Sears, MD, of Johns Hopkins University in Baltimore, told Today.com all about the dangers of frogs: “Essentially all amphibians are contaminated, often with salmonella. Eating any amphibian that is not thoroughly cooked is a risk.”

Be sure to cook your amphibians before you eat them. Advice that your parents would be proud to share.
 

Dieters should stay away from diet drinks

When a drink is labeled “diet” many assume that the calorie-free beverage is the best choice. However, one of the largest studies to date on artificial sweeteners is out to set the record straight.

American Heart Association

Artificial sweeteners, or nonnutritive sweeteners (NNS), are used in most if not all diet products to give the illusion of sweetness without the caloric guilt. Some studies say they help with weight loss for that very reason, but others say they can contribute to weight gain. So which is it?

Researchers at the University of Southern California sought to add some clarity to the research already out there.

They looked at an even-gendered split of 74 participants who drank 300 mL of drinks sweetened with NNS, table sugar, or water. The researchers then used functional MRI to see how parts of the brain responsible for appetite and cravings responded to images of high-calorie foods. They also looked at glucose, insulin, and other metabolic hormone levels, as well as how much food the participants ate at their free buffet. (In the participants’ defense, who can say no to a free buffet?)

The researchers made some interesting observations:

• Women who drank the NNS drink ate more than did the table-sugar group, but all men ate the same.
• Images of those calorie-packed goodies increased cravings and appetite for obese men and women in the NNS group, compared with the table-sugar group.
• For all participants who drank the NNS drink, there was a decrease in the hormone that tells the body it’s full.

“By studying different groups we were able to show that females and people with obesity may be more sensitive to artificial sweeteners. For these groups, drinking artificially sweetened drinks may trick the brain into feeling hungry, which may in turn result in more calories being consumed,” Kathleen Page, MD, the study’s corresponding author, said in a separate statement.

Today’s lesson? Don’t believe every label you read.
 

Instagram vegetables and the triumph of peer pressure

You and your family are sitting down for dinner. You’ve taken the time to prepare a healthy, nutritious meal. Vegetables, rice, seafood – all the right things. But the children around you refuse to partake. What can you do? Why, show them a highly liked photo of broccoli on Instagram!

Teresa Burton/IMNG Medical Media

In reality, kids will probably never like to eat their vegetables, but according to a study published in Appetite, viewing highly liked images on social media can compel adults to eat theirs.

The investigators recruited a group of 169 adults aged 18-28 (average age, 21) and showed them a series of mock Instagram posts of all sorts of food, everything from Brussels sprouts to chocolate cake, as well as nonfood images to act as a baseline. The images had a varying amount of likes. After viewing the images, study participants were offered a snack buffet consisting of grapes and cookies.

The results were a triumph of peer pressure. Those who viewed highly liked images of nutritious foods ate a significantly larger proportion of grapes, compared with those who saw highly liked images of unhealthy food or nonfood.

The authors cautioned that more research is needed, but they said that they’re onto something in the eternal struggle of getting people to eat better. If Mikey liked it, maybe you should, too. Just as long as you don’t try to encourage the eating of peas. That is a dark road none should take, and no one should ever be subjected to that cursed food.
 

It’s nice to share … hypertension?

You may have heard that, over time, you begin to resemble your spouse. You may have also heard that, as time goes by, your pet might start to resemble you, but that is a story for another time.

sabelskaya/iStock/Getty Images Plus

A lot of the time, it’s human nature that people partner with someone who is similar to them in physical and environmental status. If you like to go jogging at 5 a.m., you might want a spouse who does the same. A study done using data from couples in Japan and the Netherlands found that couples who had the same lifestyle had similar levels of blood pressure, cholesterol, and triglycerides. They also had similar illnesses such as hypertension and diabetes.

It’s important to note that many of the couples were not very genetically similar but had similar lifestyles. Encourage your partner to have a healthier lifestyle, so you can live on for many years to come!

Approximately one-third of the patients treated in the ASCENT clinical trial comparing the antibody-drug conjugate sacituzumab govitecan (Trodelvy, Gilead) with single-agent chemotherapy in patients with triple-negative breast cancer (TNBC) did not have an initial diagnosis of TNBC.

But as a subanalysis of data from the randomized, phase 3 study showed, sacituzumab govitecan was associated with significantly better progression-free survival (PFS) and overall survival among patients without an initial TNBC diagnosis, with efficacy similar to that seen in the overall study population and in patients without known brain metastases, reported Joyce O’Shaughnessy, MD, at the 2021 European Society for Medical Oncology Congress. In her presentation (abstract 258P), Dr. O’Shaughnessy, who is an oncologist with the Texas Oncology–Baylor Charles A. Sammons Cancer Center in Dallas, said that it’s not uncommon to see acquired triple-negative breast cancer in patients who have hormone receptor–positive disease initially and then later on, develop triple-negative breast cancer.

“That is why at the time of metastatic diagnosis we always say that patients should have repeat receptor [testing], because it’s been well described that a subset of hormone receptor–positive breast can become triple negative under pressure from endocrine therapy,” said ASCENT coinvestigator Aditya Bardia, MD, MPH, Massachusetts General Hospital, Boston, in an interview

Coinvestigator Kevine Punie, MD, from University Hospitals Leuven (Belgium), said that “triple-negative breast cancer is a diagnosis of exclusion. This is a heterogenous disease where several biological subsets are merged.”

“It was important to perform this subgroup analysis to reassure us that the treatment effect we see from [sacituzumab govitecan] in the overall population is also observed in this specific subgroup of patients where biologically we’re treating a different disease,” he said in an interview.
 

Antibody-drug conjugate

Sacituzumab govitecan consists of an antibody targeted to the trophoblast antigen 2 cell surface receptor found on most breast cancer cells, plus the topoisomerase-1 inhibitor SN-38 as its toxic payload.

In the primary intent-to-treat (ITT) analysis of ASCENT, sacituzumab significantly prolonged PFS with a median of 4.8 versus 1.7 months for patients treated with the physician’s choice of either capecitabine, eribulin, vinorelbine, or gemcitabine. The difference translated into an HR for progression with the antibody-drug conjugate of 0.41 (P < .00001).

The subgroup analysis looked at outcomes for 70 patients randomized to sacituzumab govitecan and 78 randomized to single-agent chemotherapy who did not have an initial diagnosis of TNBC.

In all, 27% of patients in this subgroup in the sacituzumab arm and 29% in the chemotherapy arm had received a prior line of treatment with a CDK4/6 inhibitor.

At the time of data cutoff in March 2020, four patients (6%) in the sacituzumab arm remained on treatment versus no patient in the chemotherapy arm. The most common reason for treatment discontinuation was disease progression, which occurred in 84% and 72% of patients, respectively.

The median treatment duration was 5.1 months in the sacituzumab and 1.2 months in the chemotherapy arm. The median duration of follow-up was 10.6 and 6.1 months, respectively.
 

Progression-free survival, overall survival results

For all patients without an initial TNBC diagnosis, the median PFS was 4.6 months with sacituzumab versus 2.3 months with chemotherapy, which translated into a hazard ratio for progression of 0.48 (95% confidence interval, 0.32-0.72). The progression-free benefit with the antibody-drug conjugate was similar to that seen in the intent-to-treat population, as noted before, and among the overall population of patients in the study with no known brain metastases (HR, 5.6 vs. 1.7, respectively; P < .001).

The objective response rates were 21% in the sacituzumab and 5% in the chemotherapy arm. Objective responses were not affected by the prior use of CDK 4/6 inhibitors.

Median overall survival in this subgroup was 12.4 months with the antibody-drug conjugate versus 6.7 months with chemotherapy (95% CI, 0.30-0.64).

The investigators reported that the safety profile was manageable in this subgroup of patients, with a low rate of treatment discontinuations because of adverse events (5%) and no treatment-related deaths with sacituzumab govitecan.
 

Health-related quality of life

In a separate poster (abstract 257P) presented at the meeting, the ASCENT investigators reported health-related quality of life results in the overall population.

The mean European Organization for the Research and Treatment of Cancer quality of life questionnaire subscale scores at baseline were similar between treatment arms.

For the major domains of global health status, physical and emotional functioning as well as lower symptomatic impact of fatigue, pain, dyspnea, and insomnia, sacituzumab govitecan showed “significantly and meaningfully greater improvement” than the physician’s choice of chemotherapy, the investigators found.

Of individual symptoms, only diarrhea was worse with the antibody-drug conjugate.

“These were important improvements,” Dr. Punie said, “because we saw improvements in the primary health-related quality of life domains such as global health status. We also saw that the time to clinically meaningful deterioration of quality of life domains were significantly longer for patients treated with [sacituzumab govitecan].”

“Patients who received sacituzumab govitecan had better health-related quality of life as compared to the control arm, and that’s a very important result, because in the metastatic setting our goal is twofold: We want to prolong survival, and we want patients to have improved quality of life,” Dr. Bardia said.

The Ascent trial is sponsored by Gilead Sciences. Dr. Punie disclosed relationships with multiple companies/organizations, not including Gilead. Dr. Bardia disclosed contracted research for Gilead and others, as well as other relationships.

Approximately one-third of the patients treated in the ASCENT clinical trial comparing the antibody-drug conjugate sacituzumab govitecan (Trodelvy, Gilead) with single-agent chemotherapy in patients with triple-negative breast cancer (TNBC) did not have an initial diagnosis of TNBC.

But as a subanalysis of data from the randomized, phase 3 study showed, sacituzumab govitecan was associated with significantly better progression-free survival (PFS) and overall survival among patients without an initial TNBC diagnosis, with efficacy similar to that seen in the overall study population and in patients without known brain metastases, reported Joyce O’Shaughnessy, MD, at the 2021 European Society for Medical Oncology Congress. In her presentation (abstract 258P), Dr. O’Shaughnessy, who is an oncologist with the Texas Oncology–Baylor Charles A. Sammons Cancer Center in Dallas, said that it’s not uncommon to see acquired triple-negative breast cancer in patients who have hormone receptor–positive disease initially and then later on, develop triple-negative breast cancer.

“That is why at the time of metastatic diagnosis we always say that patients should have repeat receptor [testing], because it’s been well described that a subset of hormone receptor–positive breast can become triple negative under pressure from endocrine therapy,” said ASCENT coinvestigator Aditya Bardia, MD, MPH, Massachusetts General Hospital, Boston, in an interview

Coinvestigator Kevine Punie, MD, from University Hospitals Leuven (Belgium), said that “triple-negative breast cancer is a diagnosis of exclusion. This is a heterogenous disease where several biological subsets are merged.”

“It was important to perform this subgroup analysis to reassure us that the treatment effect we see from [sacituzumab govitecan] in the overall population is also observed in this specific subgroup of patients where biologically we’re treating a different disease,” he said in an interview.
 

Antibody-drug conjugate

Sacituzumab govitecan consists of an antibody targeted to the trophoblast antigen 2 cell surface receptor found on most breast cancer cells, plus the topoisomerase-1 inhibitor SN-38 as its toxic payload.

In the primary intent-to-treat (ITT) analysis of ASCENT, sacituzumab significantly prolonged PFS with a median of 4.8 versus 1.7 months for patients treated with the physician’s choice of either capecitabine, eribulin, vinorelbine, or gemcitabine. The difference translated into an HR for progression with the antibody-drug conjugate of 0.41 (P < .00001).

The subgroup analysis looked at outcomes for 70 patients randomized to sacituzumab govitecan and 78 randomized to single-agent chemotherapy who did not have an initial diagnosis of TNBC.

In all, 27% of patients in this subgroup in the sacituzumab arm and 29% in the chemotherapy arm had received a prior line of treatment with a CDK4/6 inhibitor.

At the time of data cutoff in March 2020, four patients (6%) in the sacituzumab arm remained on treatment versus no patient in the chemotherapy arm. The most common reason for treatment discontinuation was disease progression, which occurred in 84% and 72% of patients, respectively.

The median treatment duration was 5.1 months in the sacituzumab and 1.2 months in the chemotherapy arm. The median duration of follow-up was 10.6 and 6.1 months, respectively.
 

Progression-free survival, overall survival results

For all patients without an initial TNBC diagnosis, the median PFS was 4.6 months with sacituzumab versus 2.3 months with chemotherapy, which translated into a hazard ratio for progression of 0.48 (95% confidence interval, 0.32-0.72). The progression-free benefit with the antibody-drug conjugate was similar to that seen in the intent-to-treat population, as noted before, and among the overall population of patients in the study with no known brain metastases (HR, 5.6 vs. 1.7, respectively; P < .001).

The objective response rates were 21% in the sacituzumab and 5% in the chemotherapy arm. Objective responses were not affected by the prior use of CDK 4/6 inhibitors.

Median overall survival in this subgroup was 12.4 months with the antibody-drug conjugate versus 6.7 months with chemotherapy (95% CI, 0.30-0.64).

The investigators reported that the safety profile was manageable in this subgroup of patients, with a low rate of treatment discontinuations because of adverse events (5%) and no treatment-related deaths with sacituzumab govitecan.
 

Health-related quality of life

In a separate poster (abstract 257P) presented at the meeting, the ASCENT investigators reported health-related quality of life results in the overall population.

The mean European Organization for the Research and Treatment of Cancer quality of life questionnaire subscale scores at baseline were similar between treatment arms.

For the major domains of global health status, physical and emotional functioning as well as lower symptomatic impact of fatigue, pain, dyspnea, and insomnia, sacituzumab govitecan showed “significantly and meaningfully greater improvement” than the physician’s choice of chemotherapy, the investigators found.

Of individual symptoms, only diarrhea was worse with the antibody-drug conjugate.

“These were important improvements,” Dr. Punie said, “because we saw improvements in the primary health-related quality of life domains such as global health status. We also saw that the time to clinically meaningful deterioration of quality of life domains were significantly longer for patients treated with [sacituzumab govitecan].”

“Patients who received sacituzumab govitecan had better health-related quality of life as compared to the control arm, and that’s a very important result, because in the metastatic setting our goal is twofold: We want to prolong survival, and we want patients to have improved quality of life,” Dr. Bardia said.

The Ascent trial is sponsored by Gilead Sciences. Dr. Punie disclosed relationships with multiple companies/organizations, not including Gilead. Dr. Bardia disclosed contracted research for Gilead and others, as well as other relationships.

Approximately one-third of the patients treated in the ASCENT clinical trial comparing the antibody-drug conjugate sacituzumab govitecan (Trodelvy, Gilead) with single-agent chemotherapy in patients with triple-negative breast cancer (TNBC) did not have an initial diagnosis of TNBC.

But as a subanalysis of data from the randomized, phase 3 study showed, sacituzumab govitecan was associated with significantly better progression-free survival (PFS) and overall survival among patients without an initial TNBC diagnosis, with efficacy similar to that seen in the overall study population and in patients without known brain metastases, reported Joyce O’Shaughnessy, MD, at the 2021 European Society for Medical Oncology Congress. In her presentation (abstract 258P), Dr. O’Shaughnessy, who is an oncologist with the Texas Oncology–Baylor Charles A. Sammons Cancer Center in Dallas, said that it’s not uncommon to see acquired triple-negative breast cancer in patients who have hormone receptor–positive disease initially and then later on, develop triple-negative breast cancer.

“That is why at the time of metastatic diagnosis we always say that patients should have repeat receptor [testing], because it’s been well described that a subset of hormone receptor–positive breast can become triple negative under pressure from endocrine therapy,” said ASCENT coinvestigator Aditya Bardia, MD, MPH, Massachusetts General Hospital, Boston, in an interview

Coinvestigator Kevine Punie, MD, from University Hospitals Leuven (Belgium), said that “triple-negative breast cancer is a diagnosis of exclusion. This is a heterogenous disease where several biological subsets are merged.”

“It was important to perform this subgroup analysis to reassure us that the treatment effect we see from [sacituzumab govitecan] in the overall population is also observed in this specific subgroup of patients where biologically we’re treating a different disease,” he said in an interview.
 

Antibody-drug conjugate

Sacituzumab govitecan consists of an antibody targeted to the trophoblast antigen 2 cell surface receptor found on most breast cancer cells, plus the topoisomerase-1 inhibitor SN-38 as its toxic payload.

In the primary intent-to-treat (ITT) analysis of ASCENT, sacituzumab significantly prolonged PFS with a median of 4.8 versus 1.7 months for patients treated with the physician’s choice of either capecitabine, eribulin, vinorelbine, or gemcitabine. The difference translated into an HR for progression with the antibody-drug conjugate of 0.41 (P < .00001).

The subgroup analysis looked at outcomes for 70 patients randomized to sacituzumab govitecan and 78 randomized to single-agent chemotherapy who did not have an initial diagnosis of TNBC.

In all, 27% of patients in this subgroup in the sacituzumab arm and 29% in the chemotherapy arm had received a prior line of treatment with a CDK4/6 inhibitor.

At the time of data cutoff in March 2020, four patients (6%) in the sacituzumab arm remained on treatment versus no patient in the chemotherapy arm. The most common reason for treatment discontinuation was disease progression, which occurred in 84% and 72% of patients, respectively.

The median treatment duration was 5.1 months in the sacituzumab and 1.2 months in the chemotherapy arm. The median duration of follow-up was 10.6 and 6.1 months, respectively.
 

Progression-free survival, overall survival results

For all patients without an initial TNBC diagnosis, the median PFS was 4.6 months with sacituzumab versus 2.3 months with chemotherapy, which translated into a hazard ratio for progression of 0.48 (95% confidence interval, 0.32-0.72). The progression-free benefit with the antibody-drug conjugate was similar to that seen in the intent-to-treat population, as noted before, and among the overall population of patients in the study with no known brain metastases (HR, 5.6 vs. 1.7, respectively; P < .001).

The objective response rates were 21% in the sacituzumab and 5% in the chemotherapy arm. Objective responses were not affected by the prior use of CDK 4/6 inhibitors.

Median overall survival in this subgroup was 12.4 months with the antibody-drug conjugate versus 6.7 months with chemotherapy (95% CI, 0.30-0.64).

The investigators reported that the safety profile was manageable in this subgroup of patients, with a low rate of treatment discontinuations because of adverse events (5%) and no treatment-related deaths with sacituzumab govitecan.
 

Health-related quality of life

In a separate poster (abstract 257P) presented at the meeting, the ASCENT investigators reported health-related quality of life results in the overall population.

The mean European Organization for the Research and Treatment of Cancer quality of life questionnaire subscale scores at baseline were similar between treatment arms.

For the major domains of global health status, physical and emotional functioning as well as lower symptomatic impact of fatigue, pain, dyspnea, and insomnia, sacituzumab govitecan showed “significantly and meaningfully greater improvement” than the physician’s choice of chemotherapy, the investigators found.

Of individual symptoms, only diarrhea was worse with the antibody-drug conjugate.

“These were important improvements,” Dr. Punie said, “because we saw improvements in the primary health-related quality of life domains such as global health status. We also saw that the time to clinically meaningful deterioration of quality of life domains were significantly longer for patients treated with [sacituzumab govitecan].”

“Patients who received sacituzumab govitecan had better health-related quality of life as compared to the control arm, and that’s a very important result, because in the metastatic setting our goal is twofold: We want to prolong survival, and we want patients to have improved quality of life,” Dr. Bardia said.

The Ascent trial is sponsored by Gilead Sciences. Dr. Punie disclosed relationships with multiple companies/organizations, not including Gilead. Dr. Bardia disclosed contracted research for Gilead and others, as well as other relationships.

In July 2021, University Hospitals, in Cleveland, announced that its staff had transplanted a kidney into the wrong patient. Although the patient who received the kidney was recovering well, the patient who was supposed to have received the kidney was skipped over. As a result of the error, two employees were placed on administrative leave and the incident was being investigated, the hospital announced.

In April 2020, an interventional radiologist at Boca Raton Regional Hospital, in Boca Raton, Fla., was sued for allegedly placing a stent into the wrong kidney of an 80-year-old patient. Using fluoroscopic guidance, the doctor removed an old stent from the right side but incorrectly replaced it with a new stent on the left side, according to an interview conducted by this news organization with the patient’s lawyers at Searcy Law, in West Palm Beach.

Wrong-site surgery -- surgery performed on the wrong patient, the wrong body part, or the wrong side of the body -- is a rare but distressing event and garners much attention when it happens. “The problem is that it is so rare that doctors don’t focus on it,” says Mary R. Kwaan, MD, a colorectal surgeon at UCLA Medical Center, Los Angeles.

A 2006 study in which Kwaan was the lead author concluded that there was one wrong-site surgery for every 112,994 surgeries. Those mistakes can add up. A 2006 study estimated that 25 to 52 wrong-site surgeries were performed each week in the United States.

“Many surgeons don’t think it can happen to them, so they don’t take extra precautions,” says David Mayer, MD, executive director of the MedStar Institute for Quality and Safety, in Washington, DC. “When they make a wrong-site error, usually the first thing they say is, ‘I never thought this would happen to me,’ ” he says.

Wrong-site surgeries are considered sentinel events -- the worst kinds of medical errors. The Sullivan Group, a patient safety consultancy based in Colorado, reports that in 2013, 2.7% of patients who were involved in wrong-site surgeries died and 41% experienced some type of permanent injury. The mean malpractice payment was $127,000.

Some malpractice payments are much higher. In 2013, a Maryland ob.gyn paid a $1.42 million malpractice award for removing the wrong ovary from a woman in 2009. In 2017, a Pennsylvania urologist paid $870,000 for removing the wrong testicle from a man in 2013.
 

Wrong-site surgery often involves experienced surgeons

One might think that wrong-site surgeries usually involve younger or less-experienced surgeons, but that’s not the case; two thirds of the surgeons who perform wrong-site surgeries are in their 40s and 50s, compared with fewer than 25% younger than 40.

In a rather chilling statistic, in a 2013 survey, 12.4% of doctors who were involved in sentinel events in general had claims for more than one event.

These errors are more common in certain specialties. In a study reported in the Journal of Neurology, Neurosurgery and Spine, 25% of orthopedic surgeons reported performing at least one wrong-site surgery during their career.

Within orthopedics, spine surgery is ground zero for wrong-site surgery. “Finding the site in spine surgery can be more difficult than in common left-right orthopedic procedures,” says Joseph A. Bosco III, a New York City orthopedist.

A 2007 study found that 25% of neurosurgeons had performed wrong-site surgeries. In Missouri in 2013, for example, a 53-year-old patient who was scheduled to undergo a left-sided craniotomy bypass allegedly underwent a right-sided craniotomy and was unable to speak after surgery.

Wrong-site surgeries are also performed by general surgeons, urologists, cardiologists, otolaryngologists, and ophthalmologists. A 2021 lawsuit accused a Tampa urologist of removing the patient’s wrong testicle. And a 2019 lawsuit accused a Chicago ophthalmologist of operating on the wrong eye to remove a cyst.
 

It’s not just the surgeon’s mistake

Mistakes are not only made by the surgeon in the operating room (OR). They can be made by staff when scheduling a surgery, radiologists and pathologists when writing their reports for surgery, and by team members in the OR.

Many people are prone to confusing left and right. A 2020 study found that 14.9% of people had difficulty distinguishing left from right; other studies have shown higher rates. Distractions increase the likelihood of mistakes. In a 2015 study, background noise in a hospital ward made it more difficult for medical students to make left-right judgments.

OR personnel can be confused when patients are turned around. “To operate on the back of someone’s leg, the surgeon may turn the patient from supine to prone, and so left becomes right,” says Samuel C. Seiden, MD, an anesthesiologist in Roseville, Calif., who has studied wrong-site surgery.

Operative site markings that are drawn on the skin can be rubbed off when surgical prep is applied, and markings aren’t usually possible for procedures such as spine surgeries. Surgical draping can make it harder to distinguish the patient’s left and right, and a busy surgeon relying on memory may confuse cases and perform wrong-patient surgery.
 

A push to eliminate wrong-site surgery

In 2004, the Joint Commission, which accredits hospitals and many surgery centers, decided to do something about wrong-site surgery and related surgical errors. It released a universal protocol, which requires hospitals to take three steps to prevent errors: perform preoperative verification that is based on patient care documents; mark the operative site; and take a time-out just before surgery, during which the team should consider whether a mistake is about to be made.

Two years after the Joint Commission published its protocol, Dr. Seiden led a study to determine what effect it had had. The investigators found that wrong-site cases had decreased by only about one third. Preventing wrong-site surgery “turns out to be more complicated to eradicate than anybody thought,” Mark Chassin, MD, president of the Joint Commission, stated a few years later.

Why did the protocol have only a limited effect? Dr. Seiden says that it has been hard to change doctors’ traditional attitudes against standardization. “Some have had an attitude that checklists are for dummies, but that is changing,” he says.

For instance, some surgical teams were not paying attention during time-outs. “The time-out should be like the invocation of the National Anthem,” an orthopedic surgeon from Iowa wrote. “All other activities should stop.”

Even had surgeons followed the universal protocol, about one third of wrong-site surgeries would not have been identified, according to Dr. Kwaan’s study, which was published in the same year as Dr. Seiden’s. As an example, when the wrong kidney was removed at Methodist Hospital, in St. Louis Park, Minn., the hospital said it was following a protocol set by the Minnesota Hospital Association.
 

Redoubling efforts

In 2009, the Joint Commission decided to take another tack. It encouraged hospitals to make root-cause analyses not only of wrong-site surgeries but also of near misses, which are much more plentiful. It used the insights gained to change surgical routines and protocols.

The Safe Surgery Project, a collaboration between the Joint Commission’s Center for Transforming Healthcare and eight hospitals and surgery centers, reduced the number of errors and near misses by 46% in the scheduling area, 63% in pre-op, and 51% in the OR area.

From that project, the center developed the Targeted Solutions Tool, which basically uses the same methodology that the project used. The center told this news organization that 79 healthcare organizations have used the tool and have reduced the number of errors and near misses by 56% in scheduling, 24% in pre-op, and 48% in the OR.

For this approach to work, however, surgical teams must report their errors to the hospital, which had not been done before. A 2008 study by the Office of the Inspector General of the U.S. Department of Health and Human Services found that surgical staff did not report 86% of adverse events to their hospitals. Reasons given included lack of time, fear of punitive action, and skepticism that reporting would do any good.

Unlike some other adverse events, it’s hard to keep wrong-site surgeries secret from patients, because they can usually see the scars from it, but some surgeons invent ways to cover it up from patients, too, Dr. Mayer says. One wrong-side hernia repair was corrected in mid operation. Afterward, the surgeon told the patient that he had found another hernia on the other side and had fixed that one, too.
 

Changing the culture

Reformers argue that wrong-site surgeries can be prevented by changing the culture of the hospital or surgery center. “We have to think of wrong-site surgeries as a failure of the system, not of the individual,” says Ron Savrin, MD, a general surgeon in Chagrin Falls, Ohio, who is a surgery subject matter expert for the Sullivan Group. “It should never be only up to one individual to stop an error from occurring.”

Seeing oneself as part of a team can reduce errors. Although other people can introduce errors that make a person look bad, they can also stop the errors that might otherwise have occurred. Punishing individuals for making errors does little good in stopping errors.

“It’s human nature to want to punish somebody for making a mistake, and it’s hard to change that mentality,” Dr. Savrin says. He recalls that when he was a resident, “the morbidity and mortality conferences could be very difficult for anyone who made a mistake, but I think that attitude is changing.”

Studies have found wide variation in the number of wrong-site surgeries among hospitals. A recent Pennsylvania study found an average of one wrong-site surgery or near miss per hospital per year, but about one third of hospitals did not report any.

Wrong-site surgeries are often concentrated in certain hospitals -- even prestigious teaching hospitals are not immune. A decade ago, Rhode Island Hospital had five wrong-site surgeries in 2 years, and Boston’s Beth Israel Deaconess Medical Center had three wrong-spine surgeries within 2 months.
 

Other ways to reduce errors

Dr. Seiden thinks reform efforts should take a page from his own specialty. Anesthesiology has developed a variety of forcing functions, which are simple changes in technology that can stop errors. An example is the use of a valve that will not deliver a drug unless certain steps are followed.

The StartBox System, a new way to prevent surgical errors, delivers the surgery blade only after all safety information has been provided. Tested by 11 orthopedic surgeons performing 487 procedures, the system identified 17 near misses.

Another approach is to film time-outs so as to enforce compliance with protocols and help with root-cause analyses. NYU-Langone Medical Center, in New York City, not only films the time-out but also grades OR teams on compliance, says Dr. Bosco, who is vice chair of clinical affairs in the department of orthopedic surgery at the hospital.

In addition, more states are requiring hospitals to report adverse events, including wrong-site surgeries. According to the National Academy for State Health Policy, 28 states require the reporting of adverse events. However, only six states identify facilities in public reports; 16 states publish only aggregate data; and five states do not report error data to the public.
 

The goal is zero errors

Are there fewer wrong-site surgeries now? “My sense is that surgeons, hospitals, and surgery centers are taking wrong-site errors more seriously,” Dr. Savrin says.

Because reported information is spotty and no major studies on incidence have been conducted in recent years, “we don’t have a clear idea,” he says, “but my best guess is that the rate is declining.

“Absolute zero preventable errors has to be our goal,” Dr. Savrin says “We might not get there, but we can’t stop trying.”

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

In July 2021, University Hospitals, in Cleveland, announced that its staff had transplanted a kidney into the wrong patient. Although the patient who received the kidney was recovering well, the patient who was supposed to have received the kidney was skipped over. As a result of the error, two employees were placed on administrative leave and the incident was being investigated, the hospital announced.

In April 2020, an interventional radiologist at Boca Raton Regional Hospital, in Boca Raton, Fla., was sued for allegedly placing a stent into the wrong kidney of an 80-year-old patient. Using fluoroscopic guidance, the doctor removed an old stent from the right side but incorrectly replaced it with a new stent on the left side, according to an interview conducted by this news organization with the patient’s lawyers at Searcy Law, in West Palm Beach.

Wrong-site surgery -- surgery performed on the wrong patient, the wrong body part, or the wrong side of the body -- is a rare but distressing event and garners much attention when it happens. “The problem is that it is so rare that doctors don’t focus on it,” says Mary R. Kwaan, MD, a colorectal surgeon at UCLA Medical Center, Los Angeles.

A 2006 study in which Kwaan was the lead author concluded that there was one wrong-site surgery for every 112,994 surgeries. Those mistakes can add up. A 2006 study estimated that 25 to 52 wrong-site surgeries were performed each week in the United States.

“Many surgeons don’t think it can happen to them, so they don’t take extra precautions,” says David Mayer, MD, executive director of the MedStar Institute for Quality and Safety, in Washington, DC. “When they make a wrong-site error, usually the first thing they say is, ‘I never thought this would happen to me,’ ” he says.

Wrong-site surgeries are considered sentinel events -- the worst kinds of medical errors. The Sullivan Group, a patient safety consultancy based in Colorado, reports that in 2013, 2.7% of patients who were involved in wrong-site surgeries died and 41% experienced some type of permanent injury. The mean malpractice payment was $127,000.

Some malpractice payments are much higher. In 2013, a Maryland ob.gyn paid a $1.42 million malpractice award for removing the wrong ovary from a woman in 2009. In 2017, a Pennsylvania urologist paid $870,000 for removing the wrong testicle from a man in 2013.
 

Wrong-site surgery often involves experienced surgeons

One might think that wrong-site surgeries usually involve younger or less-experienced surgeons, but that’s not the case; two thirds of the surgeons who perform wrong-site surgeries are in their 40s and 50s, compared with fewer than 25% younger than 40.

In a rather chilling statistic, in a 2013 survey, 12.4% of doctors who were involved in sentinel events in general had claims for more than one event.

These errors are more common in certain specialties. In a study reported in the Journal of Neurology, Neurosurgery and Spine, 25% of orthopedic surgeons reported performing at least one wrong-site surgery during their career.

Within orthopedics, spine surgery is ground zero for wrong-site surgery. “Finding the site in spine surgery can be more difficult than in common left-right orthopedic procedures,” says Joseph A. Bosco III, a New York City orthopedist.

A 2007 study found that 25% of neurosurgeons had performed wrong-site surgeries. In Missouri in 2013, for example, a 53-year-old patient who was scheduled to undergo a left-sided craniotomy bypass allegedly underwent a right-sided craniotomy and was unable to speak after surgery.

Wrong-site surgeries are also performed by general surgeons, urologists, cardiologists, otolaryngologists, and ophthalmologists. A 2021 lawsuit accused a Tampa urologist of removing the patient’s wrong testicle. And a 2019 lawsuit accused a Chicago ophthalmologist of operating on the wrong eye to remove a cyst.
 

It’s not just the surgeon’s mistake

Mistakes are not only made by the surgeon in the operating room (OR). They can be made by staff when scheduling a surgery, radiologists and pathologists when writing their reports for surgery, and by team members in the OR.

Many people are prone to confusing left and right. A 2020 study found that 14.9% of people had difficulty distinguishing left from right; other studies have shown higher rates. Distractions increase the likelihood of mistakes. In a 2015 study, background noise in a hospital ward made it more difficult for medical students to make left-right judgments.

OR personnel can be confused when patients are turned around. “To operate on the back of someone’s leg, the surgeon may turn the patient from supine to prone, and so left becomes right,” says Samuel C. Seiden, MD, an anesthesiologist in Roseville, Calif., who has studied wrong-site surgery.

Operative site markings that are drawn on the skin can be rubbed off when surgical prep is applied, and markings aren’t usually possible for procedures such as spine surgeries. Surgical draping can make it harder to distinguish the patient’s left and right, and a busy surgeon relying on memory may confuse cases and perform wrong-patient surgery.
 

A push to eliminate wrong-site surgery

In 2004, the Joint Commission, which accredits hospitals and many surgery centers, decided to do something about wrong-site surgery and related surgical errors. It released a universal protocol, which requires hospitals to take three steps to prevent errors: perform preoperative verification that is based on patient care documents; mark the operative site; and take a time-out just before surgery, during which the team should consider whether a mistake is about to be made.

Two years after the Joint Commission published its protocol, Dr. Seiden led a study to determine what effect it had had. The investigators found that wrong-site cases had decreased by only about one third. Preventing wrong-site surgery “turns out to be more complicated to eradicate than anybody thought,” Mark Chassin, MD, president of the Joint Commission, stated a few years later.

Why did the protocol have only a limited effect? Dr. Seiden says that it has been hard to change doctors’ traditional attitudes against standardization. “Some have had an attitude that checklists are for dummies, but that is changing,” he says.

For instance, some surgical teams were not paying attention during time-outs. “The time-out should be like the invocation of the National Anthem,” an orthopedic surgeon from Iowa wrote. “All other activities should stop.”

Even had surgeons followed the universal protocol, about one third of wrong-site surgeries would not have been identified, according to Dr. Kwaan’s study, which was published in the same year as Dr. Seiden’s. As an example, when the wrong kidney was removed at Methodist Hospital, in St. Louis Park, Minn., the hospital said it was following a protocol set by the Minnesota Hospital Association.
 

Redoubling efforts

In 2009, the Joint Commission decided to take another tack. It encouraged hospitals to make root-cause analyses not only of wrong-site surgeries but also of near misses, which are much more plentiful. It used the insights gained to change surgical routines and protocols.

The Safe Surgery Project, a collaboration between the Joint Commission’s Center for Transforming Healthcare and eight hospitals and surgery centers, reduced the number of errors and near misses by 46% in the scheduling area, 63% in pre-op, and 51% in the OR area.

From that project, the center developed the Targeted Solutions Tool, which basically uses the same methodology that the project used. The center told this news organization that 79 healthcare organizations have used the tool and have reduced the number of errors and near misses by 56% in scheduling, 24% in pre-op, and 48% in the OR.

For this approach to work, however, surgical teams must report their errors to the hospital, which had not been done before. A 2008 study by the Office of the Inspector General of the U.S. Department of Health and Human Services found that surgical staff did not report 86% of adverse events to their hospitals. Reasons given included lack of time, fear of punitive action, and skepticism that reporting would do any good.

Unlike some other adverse events, it’s hard to keep wrong-site surgeries secret from patients, because they can usually see the scars from it, but some surgeons invent ways to cover it up from patients, too, Dr. Mayer says. One wrong-side hernia repair was corrected in mid operation. Afterward, the surgeon told the patient that he had found another hernia on the other side and had fixed that one, too.
 

Changing the culture

Reformers argue that wrong-site surgeries can be prevented by changing the culture of the hospital or surgery center. “We have to think of wrong-site surgeries as a failure of the system, not of the individual,” says Ron Savrin, MD, a general surgeon in Chagrin Falls, Ohio, who is a surgery subject matter expert for the Sullivan Group. “It should never be only up to one individual to stop an error from occurring.”

Seeing oneself as part of a team can reduce errors. Although other people can introduce errors that make a person look bad, they can also stop the errors that might otherwise have occurred. Punishing individuals for making errors does little good in stopping errors.

“It’s human nature to want to punish somebody for making a mistake, and it’s hard to change that mentality,” Dr. Savrin says. He recalls that when he was a resident, “the morbidity and mortality conferences could be very difficult for anyone who made a mistake, but I think that attitude is changing.”

Studies have found wide variation in the number of wrong-site surgeries among hospitals. A recent Pennsylvania study found an average of one wrong-site surgery or near miss per hospital per year, but about one third of hospitals did not report any.

Wrong-site surgeries are often concentrated in certain hospitals -- even prestigious teaching hospitals are not immune. A decade ago, Rhode Island Hospital had five wrong-site surgeries in 2 years, and Boston’s Beth Israel Deaconess Medical Center had three wrong-spine surgeries within 2 months.
 

Other ways to reduce errors

Dr. Seiden thinks reform efforts should take a page from his own specialty. Anesthesiology has developed a variety of forcing functions, which are simple changes in technology that can stop errors. An example is the use of a valve that will not deliver a drug unless certain steps are followed.

The StartBox System, a new way to prevent surgical errors, delivers the surgery blade only after all safety information has been provided. Tested by 11 orthopedic surgeons performing 487 procedures, the system identified 17 near misses.

Another approach is to film time-outs so as to enforce compliance with protocols and help with root-cause analyses. NYU-Langone Medical Center, in New York City, not only films the time-out but also grades OR teams on compliance, says Dr. Bosco, who is vice chair of clinical affairs in the department of orthopedic surgery at the hospital.

In addition, more states are requiring hospitals to report adverse events, including wrong-site surgeries. According to the National Academy for State Health Policy, 28 states require the reporting of adverse events. However, only six states identify facilities in public reports; 16 states publish only aggregate data; and five states do not report error data to the public.
 

The goal is zero errors

Are there fewer wrong-site surgeries now? “My sense is that surgeons, hospitals, and surgery centers are taking wrong-site errors more seriously,” Dr. Savrin says.

Because reported information is spotty and no major studies on incidence have been conducted in recent years, “we don’t have a clear idea,” he says, “but my best guess is that the rate is declining.

“Absolute zero preventable errors has to be our goal,” Dr. Savrin says “We might not get there, but we can’t stop trying.”

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

In July 2021, University Hospitals, in Cleveland, announced that its staff had transplanted a kidney into the wrong patient. Although the patient who received the kidney was recovering well, the patient who was supposed to have received the kidney was skipped over. As a result of the error, two employees were placed on administrative leave and the incident was being investigated, the hospital announced.

In April 2020, an interventional radiologist at Boca Raton Regional Hospital, in Boca Raton, Fla., was sued for allegedly placing a stent into the wrong kidney of an 80-year-old patient. Using fluoroscopic guidance, the doctor removed an old stent from the right side but incorrectly replaced it with a new stent on the left side, according to an interview conducted by this news organization with the patient’s lawyers at Searcy Law, in West Palm Beach.

Wrong-site surgery -- surgery performed on the wrong patient, the wrong body part, or the wrong side of the body -- is a rare but distressing event and garners much attention when it happens. “The problem is that it is so rare that doctors don’t focus on it,” says Mary R. Kwaan, MD, a colorectal surgeon at UCLA Medical Center, Los Angeles.

A 2006 study in which Kwaan was the lead author concluded that there was one wrong-site surgery for every 112,994 surgeries. Those mistakes can add up. A 2006 study estimated that 25 to 52 wrong-site surgeries were performed each week in the United States.

“Many surgeons don’t think it can happen to them, so they don’t take extra precautions,” says David Mayer, MD, executive director of the MedStar Institute for Quality and Safety, in Washington, DC. “When they make a wrong-site error, usually the first thing they say is, ‘I never thought this would happen to me,’ ” he says.

Wrong-site surgeries are considered sentinel events -- the worst kinds of medical errors. The Sullivan Group, a patient safety consultancy based in Colorado, reports that in 2013, 2.7% of patients who were involved in wrong-site surgeries died and 41% experienced some type of permanent injury. The mean malpractice payment was $127,000.

Some malpractice payments are much higher. In 2013, a Maryland ob.gyn paid a $1.42 million malpractice award for removing the wrong ovary from a woman in 2009. In 2017, a Pennsylvania urologist paid $870,000 for removing the wrong testicle from a man in 2013.
 

Wrong-site surgery often involves experienced surgeons

One might think that wrong-site surgeries usually involve younger or less-experienced surgeons, but that’s not the case; two thirds of the surgeons who perform wrong-site surgeries are in their 40s and 50s, compared with fewer than 25% younger than 40.

In a rather chilling statistic, in a 2013 survey, 12.4% of doctors who were involved in sentinel events in general had claims for more than one event.

These errors are more common in certain specialties. In a study reported in the Journal of Neurology, Neurosurgery and Spine, 25% of orthopedic surgeons reported performing at least one wrong-site surgery during their career.

Within orthopedics, spine surgery is ground zero for wrong-site surgery. “Finding the site in spine surgery can be more difficult than in common left-right orthopedic procedures,” says Joseph A. Bosco III, a New York City orthopedist.

A 2007 study found that 25% of neurosurgeons had performed wrong-site surgeries. In Missouri in 2013, for example, a 53-year-old patient who was scheduled to undergo a left-sided craniotomy bypass allegedly underwent a right-sided craniotomy and was unable to speak after surgery.

Wrong-site surgeries are also performed by general surgeons, urologists, cardiologists, otolaryngologists, and ophthalmologists. A 2021 lawsuit accused a Tampa urologist of removing the patient’s wrong testicle. And a 2019 lawsuit accused a Chicago ophthalmologist of operating on the wrong eye to remove a cyst.
 

It’s not just the surgeon’s mistake

Mistakes are not only made by the surgeon in the operating room (OR). They can be made by staff when scheduling a surgery, radiologists and pathologists when writing their reports for surgery, and by team members in the OR.

Many people are prone to confusing left and right. A 2020 study found that 14.9% of people had difficulty distinguishing left from right; other studies have shown higher rates. Distractions increase the likelihood of mistakes. In a 2015 study, background noise in a hospital ward made it more difficult for medical students to make left-right judgments.

OR personnel can be confused when patients are turned around. “To operate on the back of someone’s leg, the surgeon may turn the patient from supine to prone, and so left becomes right,” says Samuel C. Seiden, MD, an anesthesiologist in Roseville, Calif., who has studied wrong-site surgery.

Operative site markings that are drawn on the skin can be rubbed off when surgical prep is applied, and markings aren’t usually possible for procedures such as spine surgeries. Surgical draping can make it harder to distinguish the patient’s left and right, and a busy surgeon relying on memory may confuse cases and perform wrong-patient surgery.
 

A push to eliminate wrong-site surgery

In 2004, the Joint Commission, which accredits hospitals and many surgery centers, decided to do something about wrong-site surgery and related surgical errors. It released a universal protocol, which requires hospitals to take three steps to prevent errors: perform preoperative verification that is based on patient care documents; mark the operative site; and take a time-out just before surgery, during which the team should consider whether a mistake is about to be made.

Two years after the Joint Commission published its protocol, Dr. Seiden led a study to determine what effect it had had. The investigators found that wrong-site cases had decreased by only about one third. Preventing wrong-site surgery “turns out to be more complicated to eradicate than anybody thought,” Mark Chassin, MD, president of the Joint Commission, stated a few years later.

Why did the protocol have only a limited effect? Dr. Seiden says that it has been hard to change doctors’ traditional attitudes against standardization. “Some have had an attitude that checklists are for dummies, but that is changing,” he says.

For instance, some surgical teams were not paying attention during time-outs. “The time-out should be like the invocation of the National Anthem,” an orthopedic surgeon from Iowa wrote. “All other activities should stop.”

Even had surgeons followed the universal protocol, about one third of wrong-site surgeries would not have been identified, according to Dr. Kwaan’s study, which was published in the same year as Dr. Seiden’s. As an example, when the wrong kidney was removed at Methodist Hospital, in St. Louis Park, Minn., the hospital said it was following a protocol set by the Minnesota Hospital Association.
 

Redoubling efforts

In 2009, the Joint Commission decided to take another tack. It encouraged hospitals to make root-cause analyses not only of wrong-site surgeries but also of near misses, which are much more plentiful. It used the insights gained to change surgical routines and protocols.

The Safe Surgery Project, a collaboration between the Joint Commission’s Center for Transforming Healthcare and eight hospitals and surgery centers, reduced the number of errors and near misses by 46% in the scheduling area, 63% in pre-op, and 51% in the OR area.

From that project, the center developed the Targeted Solutions Tool, which basically uses the same methodology that the project used. The center told this news organization that 79 healthcare organizations have used the tool and have reduced the number of errors and near misses by 56% in scheduling, 24% in pre-op, and 48% in the OR.

For this approach to work, however, surgical teams must report their errors to the hospital, which had not been done before. A 2008 study by the Office of the Inspector General of the U.S. Department of Health and Human Services found that surgical staff did not report 86% of adverse events to their hospitals. Reasons given included lack of time, fear of punitive action, and skepticism that reporting would do any good.

Unlike some other adverse events, it’s hard to keep wrong-site surgeries secret from patients, because they can usually see the scars from it, but some surgeons invent ways to cover it up from patients, too, Dr. Mayer says. One wrong-side hernia repair was corrected in mid operation. Afterward, the surgeon told the patient that he had found another hernia on the other side and had fixed that one, too.
 

Changing the culture

Reformers argue that wrong-site surgeries can be prevented by changing the culture of the hospital or surgery center. “We have to think of wrong-site surgeries as a failure of the system, not of the individual,” says Ron Savrin, MD, a general surgeon in Chagrin Falls, Ohio, who is a surgery subject matter expert for the Sullivan Group. “It should never be only up to one individual to stop an error from occurring.”

Seeing oneself as part of a team can reduce errors. Although other people can introduce errors that make a person look bad, they can also stop the errors that might otherwise have occurred. Punishing individuals for making errors does little good in stopping errors.

“It’s human nature to want to punish somebody for making a mistake, and it’s hard to change that mentality,” Dr. Savrin says. He recalls that when he was a resident, “the morbidity and mortality conferences could be very difficult for anyone who made a mistake, but I think that attitude is changing.”

Studies have found wide variation in the number of wrong-site surgeries among hospitals. A recent Pennsylvania study found an average of one wrong-site surgery or near miss per hospital per year, but about one third of hospitals did not report any.

Wrong-site surgeries are often concentrated in certain hospitals -- even prestigious teaching hospitals are not immune. A decade ago, Rhode Island Hospital had five wrong-site surgeries in 2 years, and Boston’s Beth Israel Deaconess Medical Center had three wrong-spine surgeries within 2 months.
 

Other ways to reduce errors

Dr. Seiden thinks reform efforts should take a page from his own specialty. Anesthesiology has developed a variety of forcing functions, which are simple changes in technology that can stop errors. An example is the use of a valve that will not deliver a drug unless certain steps are followed.

The StartBox System, a new way to prevent surgical errors, delivers the surgery blade only after all safety information has been provided. Tested by 11 orthopedic surgeons performing 487 procedures, the system identified 17 near misses.

Another approach is to film time-outs so as to enforce compliance with protocols and help with root-cause analyses. NYU-Langone Medical Center, in New York City, not only films the time-out but also grades OR teams on compliance, says Dr. Bosco, who is vice chair of clinical affairs in the department of orthopedic surgery at the hospital.

In addition, more states are requiring hospitals to report adverse events, including wrong-site surgeries. According to the National Academy for State Health Policy, 28 states require the reporting of adverse events. However, only six states identify facilities in public reports; 16 states publish only aggregate data; and five states do not report error data to the public.
 

The goal is zero errors

Are there fewer wrong-site surgeries now? “My sense is that surgeons, hospitals, and surgery centers are taking wrong-site errors more seriously,” Dr. Savrin says.

Because reported information is spotty and no major studies on incidence have been conducted in recent years, “we don’t have a clear idea,” he says, “but my best guess is that the rate is declining.

“Absolute zero preventable errors has to be our goal,” Dr. Savrin says “We might not get there, but we can’t stop trying.”

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

The extent of pathological response to neoadjuvant immune checkpoint inhibition independently predicted overall survival (OS) and disease-free survival (DFS) in patients with early-stage non–small cell lung cancer (NSCLC) in the phase 2 IFCT-1601 IONESCO trial.

Although major pathological response after neoadjuvant cisplatin-based chemotherapy has been shown to predict survival in patients with early-stage NSCLC, this is the first time a similar association has been demonstrated with neoadjuvant immune checkpoint inhibition, Marie Wislez, MD, PhD, a researcher at Hopital Cochin, Paris, reported at the 2021 European Society of Medical Oncology Congress.

Primary outcomes of the multicenter trial showed 12- and 18-month OS of 89.1%, and 12- and 18-month DFS of 78.3% and 73.7%, respectively, in 46 patients treated with preoperative durvalumab. Median OS and DFS were not reached.

Major pathological response was observed in eight patients (18.6%), with three patients experiencing complete pathological response. No deaths or recurrences were observed in patients in this group. A significant association was observed between major pathological response and DFS. However, the study was stopped early because of excessive 90-day postoperative mortality, which the authors said were most likely related to comorbidities.

The current post hoc analysis of data from the study showed poorer overall survival and disease-free survival with increasing percentage of residual viable tumor (RVT) cells on multivariate prognostic analysis (hazard ratio, 1.05 and 1.06; P = .04 and .02, respectively), Dr. Wislez said in her presentation made on Sept. 18 (abstract 1151MO).

“For each 10% increase of RVT, you have an increased risk of death of 64% and increased risk of recurrence of 71%,” she said.

Study subjects, who were enrolled between April 2017 and August 2019, had a median age of 61 years, 67.4% were men, 98% were smokers or former smokes, and all had Eastern Cooperative Oncology Group performance status scores of 0-1. The median percentage of RVT cells was 36.11.

Of the 50 patients enrolled, 46 were eligible for and received durvalumab and 43 underwent surgery. Those with stages IB and 4 cm or greater tumor size to stage IIIA non-N2 NSCLC received three cycles of durvalumab before surgery. Durvalumab was given intravenously at a dose of 750 mg on days 1, 15, and 29, and surgery was performed 2-14 days after the last infusion.

Tissue specimens from patients who underwent neoadjuvant durvalumab and complete surgical resection were retrospectively evaluated by two pathologists blinded to patient outcomes, Dr. Wislez noted.

Session chair Michael Thomas, MD, of Thoraxklinik-Heidelberg at Heidelberg (Germany) University Hospital, described the study as “hypotheses generating,” and noted that it suggests incremental step-wise assessment of pathological response could be an additional tool for subgrouping of patients in upcoming trials.

Indeed, this novel finding suggests that the extent of pathological response could be considered as a surrogate marker for neoadjuvant treatment trials, although the use of a continuous variable would be challenging in the trial setting, Dr. Wislez agreed.

“But it’s a demonstration that [with] immunotherapy monotherapy ... the extent of pathological response is associated with overall survival,” she said.

This study was funded by AstraZeneca. Dr. Wislez reported honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche, Novartis, Merck, and MSD.

[email protected]

The extent of pathological response to neoadjuvant immune checkpoint inhibition independently predicted overall survival (OS) and disease-free survival (DFS) in patients with early-stage non–small cell lung cancer (NSCLC) in the phase 2 IFCT-1601 IONESCO trial.

Although major pathological response after neoadjuvant cisplatin-based chemotherapy has been shown to predict survival in patients with early-stage NSCLC, this is the first time a similar association has been demonstrated with neoadjuvant immune checkpoint inhibition, Marie Wislez, MD, PhD, a researcher at Hopital Cochin, Paris, reported at the 2021 European Society of Medical Oncology Congress.

Primary outcomes of the multicenter trial showed 12- and 18-month OS of 89.1%, and 12- and 18-month DFS of 78.3% and 73.7%, respectively, in 46 patients treated with preoperative durvalumab. Median OS and DFS were not reached.

Major pathological response was observed in eight patients (18.6%), with three patients experiencing complete pathological response. No deaths or recurrences were observed in patients in this group. A significant association was observed between major pathological response and DFS. However, the study was stopped early because of excessive 90-day postoperative mortality, which the authors said were most likely related to comorbidities.

The current post hoc analysis of data from the study showed poorer overall survival and disease-free survival with increasing percentage of residual viable tumor (RVT) cells on multivariate prognostic analysis (hazard ratio, 1.05 and 1.06; P = .04 and .02, respectively), Dr. Wislez said in her presentation made on Sept. 18 (abstract 1151MO).

“For each 10% increase of RVT, you have an increased risk of death of 64% and increased risk of recurrence of 71%,” she said.

Study subjects, who were enrolled between April 2017 and August 2019, had a median age of 61 years, 67.4% were men, 98% were smokers or former smokes, and all had Eastern Cooperative Oncology Group performance status scores of 0-1. The median percentage of RVT cells was 36.11.

Of the 50 patients enrolled, 46 were eligible for and received durvalumab and 43 underwent surgery. Those with stages IB and 4 cm or greater tumor size to stage IIIA non-N2 NSCLC received three cycles of durvalumab before surgery. Durvalumab was given intravenously at a dose of 750 mg on days 1, 15, and 29, and surgery was performed 2-14 days after the last infusion.

Tissue specimens from patients who underwent neoadjuvant durvalumab and complete surgical resection were retrospectively evaluated by two pathologists blinded to patient outcomes, Dr. Wislez noted.

Session chair Michael Thomas, MD, of Thoraxklinik-Heidelberg at Heidelberg (Germany) University Hospital, described the study as “hypotheses generating,” and noted that it suggests incremental step-wise assessment of pathological response could be an additional tool for subgrouping of patients in upcoming trials.

Indeed, this novel finding suggests that the extent of pathological response could be considered as a surrogate marker for neoadjuvant treatment trials, although the use of a continuous variable would be challenging in the trial setting, Dr. Wislez agreed.

“But it’s a demonstration that [with] immunotherapy monotherapy ... the extent of pathological response is associated with overall survival,” she said.

This study was funded by AstraZeneca. Dr. Wislez reported honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche, Novartis, Merck, and MSD.

[email protected]

The extent of pathological response to neoadjuvant immune checkpoint inhibition independently predicted overall survival (OS) and disease-free survival (DFS) in patients with early-stage non–small cell lung cancer (NSCLC) in the phase 2 IFCT-1601 IONESCO trial.

Although major pathological response after neoadjuvant cisplatin-based chemotherapy has been shown to predict survival in patients with early-stage NSCLC, this is the first time a similar association has been demonstrated with neoadjuvant immune checkpoint inhibition, Marie Wislez, MD, PhD, a researcher at Hopital Cochin, Paris, reported at the 2021 European Society of Medical Oncology Congress.

Primary outcomes of the multicenter trial showed 12- and 18-month OS of 89.1%, and 12- and 18-month DFS of 78.3% and 73.7%, respectively, in 46 patients treated with preoperative durvalumab. Median OS and DFS were not reached.

Major pathological response was observed in eight patients (18.6%), with three patients experiencing complete pathological response. No deaths or recurrences were observed in patients in this group. A significant association was observed between major pathological response and DFS. However, the study was stopped early because of excessive 90-day postoperative mortality, which the authors said were most likely related to comorbidities.

The current post hoc analysis of data from the study showed poorer overall survival and disease-free survival with increasing percentage of residual viable tumor (RVT) cells on multivariate prognostic analysis (hazard ratio, 1.05 and 1.06; P = .04 and .02, respectively), Dr. Wislez said in her presentation made on Sept. 18 (abstract 1151MO).

“For each 10% increase of RVT, you have an increased risk of death of 64% and increased risk of recurrence of 71%,” she said.

Study subjects, who were enrolled between April 2017 and August 2019, had a median age of 61 years, 67.4% were men, 98% were smokers or former smokes, and all had Eastern Cooperative Oncology Group performance status scores of 0-1. The median percentage of RVT cells was 36.11.

Of the 50 patients enrolled, 46 were eligible for and received durvalumab and 43 underwent surgery. Those with stages IB and 4 cm or greater tumor size to stage IIIA non-N2 NSCLC received three cycles of durvalumab before surgery. Durvalumab was given intravenously at a dose of 750 mg on days 1, 15, and 29, and surgery was performed 2-14 days after the last infusion.

Tissue specimens from patients who underwent neoadjuvant durvalumab and complete surgical resection were retrospectively evaluated by two pathologists blinded to patient outcomes, Dr. Wislez noted.

Session chair Michael Thomas, MD, of Thoraxklinik-Heidelberg at Heidelberg (Germany) University Hospital, described the study as “hypotheses generating,” and noted that it suggests incremental step-wise assessment of pathological response could be an additional tool for subgrouping of patients in upcoming trials.

Indeed, this novel finding suggests that the extent of pathological response could be considered as a surrogate marker for neoadjuvant treatment trials, although the use of a continuous variable would be challenging in the trial setting, Dr. Wislez agreed.

“But it’s a demonstration that [with] immunotherapy monotherapy ... the extent of pathological response is associated with overall survival,” she said.

This study was funded by AstraZeneca. Dr. Wislez reported honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche, Novartis, Merck, and MSD.

[email protected]

COVID vaccination rates among pregnant people remain low, despite data that shows the vaccines can prevent the high risk of severe disease during pregnancy.

About 30% of pregnant people are vaccinated, according to the latest CDC data, with only 18% obtaining a dose during pregnancy. Health officials have been tracking the timing of vaccination before and during pregnancy.

The vaccination rates are even lower among pregnant Black people, CDC data shows. About 15% are fully vaccinated, compared with 25% of pregnant Hispanic and Latino people, 34% of pregnant White people, and 46% of pregnant Asian people.

“This puts them at severe risk of severe disease from COVID-19,” Rochelle Walensky, MD, the CDC director, said during a news briefing with the White House COVID-19 Response Team.

“We know that pregnant women are at increased risk of severe disease, of hospitalization and ventilation,” she said. “They’re also at increased risk for adverse events to their baby.”

Those who give birth while infected with COVID-19 had “significantly higher rates” of intensive care unit admission, intubation, ventilation, and death, according to a recent study published in JAMA Network Open.

Dr. Walensky said on Sept. 28 that studies show COVID-19 vaccines can be taken at any time while pregnant or breastfeeding. She noted that the vaccines are safe for both mothers and their babies.

“We’ve actually seen that some antibody from the vaccine traverses [the placenta] to the baby and, in fact, could potentially protect the baby,” she said.

Public health officials say the low vaccination rates can be attributed to caution around the time of pregnancy, concern for the baby, barriers to health care, and misinformation promoted online.

“Pregnancy is a precious time. It’s also a time that a lot of women have fear,” Pam Oliver, MD, an obstetrics and gynecology doctor and executive vice president of North Carolina’s Novant Health, told USA Today.

“It is natural to have questions,” she said. “So, let’s talk about what we know, let’s put it in perspective.”

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

COVID vaccination rates among pregnant people remain low, despite data that shows the vaccines can prevent the high risk of severe disease during pregnancy.

About 30% of pregnant people are vaccinated, according to the latest CDC data, with only 18% obtaining a dose during pregnancy. Health officials have been tracking the timing of vaccination before and during pregnancy.

The vaccination rates are even lower among pregnant Black people, CDC data shows. About 15% are fully vaccinated, compared with 25% of pregnant Hispanic and Latino people, 34% of pregnant White people, and 46% of pregnant Asian people.

“This puts them at severe risk of severe disease from COVID-19,” Rochelle Walensky, MD, the CDC director, said during a news briefing with the White House COVID-19 Response Team.

“We know that pregnant women are at increased risk of severe disease, of hospitalization and ventilation,” she said. “They’re also at increased risk for adverse events to their baby.”

Those who give birth while infected with COVID-19 had “significantly higher rates” of intensive care unit admission, intubation, ventilation, and death, according to a recent study published in JAMA Network Open.

Dr. Walensky said on Sept. 28 that studies show COVID-19 vaccines can be taken at any time while pregnant or breastfeeding. She noted that the vaccines are safe for both mothers and their babies.

“We’ve actually seen that some antibody from the vaccine traverses [the placenta] to the baby and, in fact, could potentially protect the baby,” she said.

Public health officials say the low vaccination rates can be attributed to caution around the time of pregnancy, concern for the baby, barriers to health care, and misinformation promoted online.

“Pregnancy is a precious time. It’s also a time that a lot of women have fear,” Pam Oliver, MD, an obstetrics and gynecology doctor and executive vice president of North Carolina’s Novant Health, told USA Today.

“It is natural to have questions,” she said. “So, let’s talk about what we know, let’s put it in perspective.”

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

COVID vaccination rates among pregnant people remain low, despite data that shows the vaccines can prevent the high risk of severe disease during pregnancy.

About 30% of pregnant people are vaccinated, according to the latest CDC data, with only 18% obtaining a dose during pregnancy. Health officials have been tracking the timing of vaccination before and during pregnancy.

The vaccination rates are even lower among pregnant Black people, CDC data shows. About 15% are fully vaccinated, compared with 25% of pregnant Hispanic and Latino people, 34% of pregnant White people, and 46% of pregnant Asian people.

“This puts them at severe risk of severe disease from COVID-19,” Rochelle Walensky, MD, the CDC director, said during a news briefing with the White House COVID-19 Response Team.

“We know that pregnant women are at increased risk of severe disease, of hospitalization and ventilation,” she said. “They’re also at increased risk for adverse events to their baby.”

Those who give birth while infected with COVID-19 had “significantly higher rates” of intensive care unit admission, intubation, ventilation, and death, according to a recent study published in JAMA Network Open.

Dr. Walensky said on Sept. 28 that studies show COVID-19 vaccines can be taken at any time while pregnant or breastfeeding. She noted that the vaccines are safe for both mothers and their babies.

“We’ve actually seen that some antibody from the vaccine traverses [the placenta] to the baby and, in fact, could potentially protect the baby,” she said.

Public health officials say the low vaccination rates can be attributed to caution around the time of pregnancy, concern for the baby, barriers to health care, and misinformation promoted online.

“Pregnancy is a precious time. It’s also a time that a lot of women have fear,” Pam Oliver, MD, an obstetrics and gynecology doctor and executive vice president of North Carolina’s Novant Health, told USA Today.

“It is natural to have questions,” she said. “So, let’s talk about what we know, let’s put it in perspective.”

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

The U.S. Food and Drug Administration has granted accelerated approval to tisotumab vedotin-tftv (Tivdak, Seagen/Genmab) for the treatment of adult patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy.

There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.

In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”

“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.

Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
 

Details of clinical trial data

The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.

The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.

All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.

The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.

The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.

Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.

Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.

The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
 

Confirmatory trial underway

Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.

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

The U.S. Food and Drug Administration has granted accelerated approval to tisotumab vedotin-tftv (Tivdak, Seagen/Genmab) for the treatment of adult patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy.

There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.

In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”

“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.

Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
 

Details of clinical trial data

The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.

The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.

All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.

The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.

The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.

Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.

Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.

The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
 

Confirmatory trial underway

Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.

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

The U.S. Food and Drug Administration has granted accelerated approval to tisotumab vedotin-tftv (Tivdak, Seagen/Genmab) for the treatment of adult patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy.

There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.

In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”

“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.

Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
 

Details of clinical trial data

The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.

The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.

All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.

The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.

The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.

Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.

Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.

The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
 

Confirmatory trial underway

Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.

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