News

TOPLINE:

Transcatheter arterial chemoembolization (TACE), a standard treatment for liver metastases from colorectal cancer, shows promise for treating locally advanced rectal tumors.

METHODOLOGY:

• The combination of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy is the current standard of care for locally advanced rectal cancer. But with pathological complete response rates of only 10%-15% and more than 30% of patients developing distant metastases within 3 years, outcomes remain suboptimal.
• Chinese investigators took a step to improve the situation, applying TACE — a standard treatment for colorectal liver metastases — to rectal tumors, dubbing the approach transcatheter rectal arterial chemoembolization (TRACE).
• As in TACE, TRACE uses precisely injected chemotherapeutic and vaso-occlusive agents to shut down blood flow to tumors, starving them of oxygen and nutrients.
• The research team tried the approach in 111 patients with stage II or III rectal tumors and performance status scores of 0-1.
• TRACE was delivered with oxaliplatin and followed by radiotherapy and S1 chemotherapy (tegafur, gimeracil, and potassium oteracil). Total mesorectal excisions were performed 4-8 weeks later, followed by mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (oxaliplatin and capecitabine) chemotherapy for 4-6 months.

TAKEAWAY:

• Overall, 20.7% of patients undergoing TRACE had a pathological complete response, and almost half (48.65%) had a major pathological response.
• Nearly 62% of patients were disease-free at 5 years, and almost 75% were alive at 5 years.
• No serious surgical complications occurred, but 21.6% of patients had postoperative complications. Overall, about 26% of patients (29 of 111) had grade 3/4 toxicities.

IN PRACTICE:

“The addition of transcatheter rectal arterial chemoembolisation to the neoadjuvant therapy can improve the pathological remission rate and prognosis in patients with locally advanced rectal cancer, without increasing the incidence of preoperative adverse events and postoperative complications,” the researchers concluded. “Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with [locally advanced rectal cancer] should be considered.”

SOURCE:

The work, led by W. Yang of the Army Medical University in Chongqing, China, was published in Clinical Oncology.

LIMITATIONS:

The study was performed at a single center with no control arm in a Chinese population.

DISCLOSURES:

The work was funded by the Third Military Medical University in China. The investigators had no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Transcatheter arterial chemoembolization (TACE), a standard treatment for liver metastases from colorectal cancer, shows promise for treating locally advanced rectal tumors.

METHODOLOGY:

• The combination of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy is the current standard of care for locally advanced rectal cancer. But with pathological complete response rates of only 10%-15% and more than 30% of patients developing distant metastases within 3 years, outcomes remain suboptimal.
• Chinese investigators took a step to improve the situation, applying TACE — a standard treatment for colorectal liver metastases — to rectal tumors, dubbing the approach transcatheter rectal arterial chemoembolization (TRACE).
• As in TACE, TRACE uses precisely injected chemotherapeutic and vaso-occlusive agents to shut down blood flow to tumors, starving them of oxygen and nutrients.
• The research team tried the approach in 111 patients with stage II or III rectal tumors and performance status scores of 0-1.
• TRACE was delivered with oxaliplatin and followed by radiotherapy and S1 chemotherapy (tegafur, gimeracil, and potassium oteracil). Total mesorectal excisions were performed 4-8 weeks later, followed by mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (oxaliplatin and capecitabine) chemotherapy for 4-6 months.

TAKEAWAY:

• Overall, 20.7% of patients undergoing TRACE had a pathological complete response, and almost half (48.65%) had a major pathological response.
• Nearly 62% of patients were disease-free at 5 years, and almost 75% were alive at 5 years.
• No serious surgical complications occurred, but 21.6% of patients had postoperative complications. Overall, about 26% of patients (29 of 111) had grade 3/4 toxicities.

IN PRACTICE:

“The addition of transcatheter rectal arterial chemoembolisation to the neoadjuvant therapy can improve the pathological remission rate and prognosis in patients with locally advanced rectal cancer, without increasing the incidence of preoperative adverse events and postoperative complications,” the researchers concluded. “Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with [locally advanced rectal cancer] should be considered.”

SOURCE:

The work, led by W. Yang of the Army Medical University in Chongqing, China, was published in Clinical Oncology.

LIMITATIONS:

The study was performed at a single center with no control arm in a Chinese population.

DISCLOSURES:

The work was funded by the Third Military Medical University in China. The investigators had no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Transcatheter arterial chemoembolization (TACE), a standard treatment for liver metastases from colorectal cancer, shows promise for treating locally advanced rectal tumors.

METHODOLOGY:

• The combination of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy is the current standard of care for locally advanced rectal cancer. But with pathological complete response rates of only 10%-15% and more than 30% of patients developing distant metastases within 3 years, outcomes remain suboptimal.
• Chinese investigators took a step to improve the situation, applying TACE — a standard treatment for colorectal liver metastases — to rectal tumors, dubbing the approach transcatheter rectal arterial chemoembolization (TRACE).
• As in TACE, TRACE uses precisely injected chemotherapeutic and vaso-occlusive agents to shut down blood flow to tumors, starving them of oxygen and nutrients.
• The research team tried the approach in 111 patients with stage II or III rectal tumors and performance status scores of 0-1.
• TRACE was delivered with oxaliplatin and followed by radiotherapy and S1 chemotherapy (tegafur, gimeracil, and potassium oteracil). Total mesorectal excisions were performed 4-8 weeks later, followed by mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (oxaliplatin and capecitabine) chemotherapy for 4-6 months.

TAKEAWAY:

• Overall, 20.7% of patients undergoing TRACE had a pathological complete response, and almost half (48.65%) had a major pathological response.
• Nearly 62% of patients were disease-free at 5 years, and almost 75% were alive at 5 years.
• No serious surgical complications occurred, but 21.6% of patients had postoperative complications. Overall, about 26% of patients (29 of 111) had grade 3/4 toxicities.

IN PRACTICE:

“The addition of transcatheter rectal arterial chemoembolisation to the neoadjuvant therapy can improve the pathological remission rate and prognosis in patients with locally advanced rectal cancer, without increasing the incidence of preoperative adverse events and postoperative complications,” the researchers concluded. “Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with [locally advanced rectal cancer] should be considered.”

SOURCE:

The work, led by W. Yang of the Army Medical University in Chongqing, China, was published in Clinical Oncology.

LIMITATIONS:

The study was performed at a single center with no control arm in a Chinese population.

DISCLOSURES:

The work was funded by the Third Military Medical University in China. The investigators had no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

ChatGPT (version 3.5) provides relatively poor and inconsistent responses when asked about appropriate colorectal cancer (CRC) screening and surveillance, a new study showed.

METHODOLOGY:

• Three board-certified gastroenterologists with 10+ years of clinical experience developed five CRC screening and five CRC surveillance clinical vignettes (with multiple choice answers), which were fed to ChatGPT version 3.5.
• ChatGPT’s responses were recorded over four separate sessions and screened for accuracy to determine reliability of the tool.
• The average number of correct answers was compared to that of 238 gastroenterologists and colorectal surgeons answering the same questions with and without the help of a previously validated CRC screening mobile app.

TAKEAWAY:

• ChatGPT’s average overall performance was 45%; the average number of correct answers was 2.75 for screening and 1.75 for surveillance.
• ChatGPT’s responses were inconsistent in a large proportion of questions; the tool gave a different answer in four questions among the different sessions.
• The average number of total correct answers of ChatGPT was significantly lower (P < .001) than that of physicians with and without the mobile app (7.71 and 5.62 correct answers, respectively).

IN PRACTICE:

“The use of validated mobile apps with decision-making algorithms could serve as more reliable assistants until large language models developed with AI are further refined,” the authors concluded.

SOURCE:

The study, with first author Lisandro Pereyra, MD, Department of Gastroenterology, Hospital Alemán of Buenos Aires, Argentina, was published online on February 7, 2024, in the Journal of Clinical Gastroenterology.

LIMITATIONS:

The 10 clinical vignettes represented a relatively small sample size to assess accuracy. The study did not use the latest version of ChatGPT. No “fine-tuning” attempts with inputs of diverse prompts, instructions, or relevant data were performed, which could potentially improve the performance of the chatbot.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

ChatGPT (version 3.5) provides relatively poor and inconsistent responses when asked about appropriate colorectal cancer (CRC) screening and surveillance, a new study showed.

METHODOLOGY:

• Three board-certified gastroenterologists with 10+ years of clinical experience developed five CRC screening and five CRC surveillance clinical vignettes (with multiple choice answers), which were fed to ChatGPT version 3.5.
• ChatGPT’s responses were recorded over four separate sessions and screened for accuracy to determine reliability of the tool.
• The average number of correct answers was compared to that of 238 gastroenterologists and colorectal surgeons answering the same questions with and without the help of a previously validated CRC screening mobile app.

TAKEAWAY:

• ChatGPT’s average overall performance was 45%; the average number of correct answers was 2.75 for screening and 1.75 for surveillance.
• ChatGPT’s responses were inconsistent in a large proportion of questions; the tool gave a different answer in four questions among the different sessions.
• The average number of total correct answers of ChatGPT was significantly lower (P < .001) than that of physicians with and without the mobile app (7.71 and 5.62 correct answers, respectively).

IN PRACTICE:

“The use of validated mobile apps with decision-making algorithms could serve as more reliable assistants until large language models developed with AI are further refined,” the authors concluded.

SOURCE:

The study, with first author Lisandro Pereyra, MD, Department of Gastroenterology, Hospital Alemán of Buenos Aires, Argentina, was published online on February 7, 2024, in the Journal of Clinical Gastroenterology.

LIMITATIONS:

The 10 clinical vignettes represented a relatively small sample size to assess accuracy. The study did not use the latest version of ChatGPT. No “fine-tuning” attempts with inputs of diverse prompts, instructions, or relevant data were performed, which could potentially improve the performance of the chatbot.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

ChatGPT (version 3.5) provides relatively poor and inconsistent responses when asked about appropriate colorectal cancer (CRC) screening and surveillance, a new study showed.

METHODOLOGY:

• Three board-certified gastroenterologists with 10+ years of clinical experience developed five CRC screening and five CRC surveillance clinical vignettes (with multiple choice answers), which were fed to ChatGPT version 3.5.
• ChatGPT’s responses were recorded over four separate sessions and screened for accuracy to determine reliability of the tool.
• The average number of correct answers was compared to that of 238 gastroenterologists and colorectal surgeons answering the same questions with and without the help of a previously validated CRC screening mobile app.

TAKEAWAY:

• ChatGPT’s average overall performance was 45%; the average number of correct answers was 2.75 for screening and 1.75 for surveillance.
• ChatGPT’s responses were inconsistent in a large proportion of questions; the tool gave a different answer in four questions among the different sessions.
• The average number of total correct answers of ChatGPT was significantly lower (P < .001) than that of physicians with and without the mobile app (7.71 and 5.62 correct answers, respectively).

IN PRACTICE:

“The use of validated mobile apps with decision-making algorithms could serve as more reliable assistants until large language models developed with AI are further refined,” the authors concluded.

SOURCE:

The study, with first author Lisandro Pereyra, MD, Department of Gastroenterology, Hospital Alemán of Buenos Aires, Argentina, was published online on February 7, 2024, in the Journal of Clinical Gastroenterology.

LIMITATIONS:

The 10 clinical vignettes represented a relatively small sample size to assess accuracy. The study did not use the latest version of ChatGPT. No “fine-tuning” attempts with inputs of diverse prompts, instructions, or relevant data were performed, which could potentially improve the performance of the chatbot.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Habitual consumption of caffeine is not associated with frequency, duration, or intensity of episodic migraines, a new study showed. Investigators said the findings suggest caffeine restrictions in migraineurs may not be necessary.

METHODOLOGY:

• The secondary analysis of a prospective cohort study on sleep in adults with episodic migraine (with or without aura) included a group of 97 people (median age, 31 years; 82% White) with an average of 5.0 ± 3.6  days per month at baseline.
• Participants provided sociodemographic information, medical history, habitual caffeinated beverage consumption, alcohol intake, and lifestyle and psychosocial factors and completed the Center for Epidemiologic Studies- scale, the Perceived Stress Scale, and the Pittsburgh Sleep Quality Index.
• Additionally, they completed twice-daily electronic diaries for the subsequent 6 weeks, reporting headache activity and the use of medications to treat the headache.

TAKEAWAY:

• A total of 67% of participants reported one to two servings of caffeinated beverages per day, 12% reported three to four servings per day, and 21% reported no habitual caffeine consumption.
• After adjusting for age, sex, oral  use, and other confounders, mean headache frequency was similar among groups (7.1 days for no caffeine, 7.4 days for one to two servings, and 5.9 days for three to four servings).
• Similarly, adjusted mean headache duration did not differ across levels of caffeinated beverage intake (8.6 hours for no caffeine, 8.5 hours for one to two servings, and 8.8 hours for three to four servings).
• Adjusted mean headache intensity also did not differ among groups.

IN PRACTICE:

“Our findings do not support a recommendation for people with episodic migraine to avoid habitual caffeinated beverage intake,” the authors wrote. However, they noted that habitual caffeine intake may affect systems involved in pain modulation via adenosine signaling. «Therefore, it is possible that habitual caffeine use in those with migraine does not significantly alter adenosine signaling, but significant changes above or below usual consumption may serve as a trigger or contribute to lowering the threshold for an attack to occur along with other triggers,» they added.

SOURCE:

Suzanne M. Bertisch, MD, MPH, assistant professor of medicine, Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, was the senior and corresponding author of the study. It was published online in Headache.

LIMITATIONS:

Serving size was not standardized, and there was no information on the type of caffeinated beverage consumed or about other sources of caffeine. Moreover, the population consisted of relatively healthy participants with episodic migraine and generally low levels of habitual caffeinated beverage intake, which limited the statistical power to detect an association between migraine frequency, duration, and intensity with higher levels of caffeine intake.

DISCLOSURES:

The study was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, and the Harvard Catalyst/Harvard Clinical and Translational Science Center. Dr. Bertisch has done consulting work with Idorsia and ResMed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Habitual consumption of caffeine is not associated with frequency, duration, or intensity of episodic migraines, a new study showed. Investigators said the findings suggest caffeine restrictions in migraineurs may not be necessary.

METHODOLOGY:

• The secondary analysis of a prospective cohort study on sleep in adults with episodic migraine (with or without aura) included a group of 97 people (median age, 31 years; 82% White) with an average of 5.0 ± 3.6  days per month at baseline.
• Participants provided sociodemographic information, medical history, habitual caffeinated beverage consumption, alcohol intake, and lifestyle and psychosocial factors and completed the Center for Epidemiologic Studies- scale, the Perceived Stress Scale, and the Pittsburgh Sleep Quality Index.
• Additionally, they completed twice-daily electronic diaries for the subsequent 6 weeks, reporting headache activity and the use of medications to treat the headache.

TAKEAWAY:

• A total of 67% of participants reported one to two servings of caffeinated beverages per day, 12% reported three to four servings per day, and 21% reported no habitual caffeine consumption.
• After adjusting for age, sex, oral  use, and other confounders, mean headache frequency was similar among groups (7.1 days for no caffeine, 7.4 days for one to two servings, and 5.9 days for three to four servings).
• Similarly, adjusted mean headache duration did not differ across levels of caffeinated beverage intake (8.6 hours for no caffeine, 8.5 hours for one to two servings, and 8.8 hours for three to four servings).
• Adjusted mean headache intensity also did not differ among groups.

IN PRACTICE:

“Our findings do not support a recommendation for people with episodic migraine to avoid habitual caffeinated beverage intake,” the authors wrote. However, they noted that habitual caffeine intake may affect systems involved in pain modulation via adenosine signaling. «Therefore, it is possible that habitual caffeine use in those with migraine does not significantly alter adenosine signaling, but significant changes above or below usual consumption may serve as a trigger or contribute to lowering the threshold for an attack to occur along with other triggers,» they added.

SOURCE:

Suzanne M. Bertisch, MD, MPH, assistant professor of medicine, Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, was the senior and corresponding author of the study. It was published online in Headache.

LIMITATIONS:

Serving size was not standardized, and there was no information on the type of caffeinated beverage consumed or about other sources of caffeine. Moreover, the population consisted of relatively healthy participants with episodic migraine and generally low levels of habitual caffeinated beverage intake, which limited the statistical power to detect an association between migraine frequency, duration, and intensity with higher levels of caffeine intake.

DISCLOSURES:

The study was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, and the Harvard Catalyst/Harvard Clinical and Translational Science Center. Dr. Bertisch has done consulting work with Idorsia and ResMed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Habitual consumption of caffeine is not associated with frequency, duration, or intensity of episodic migraines, a new study showed. Investigators said the findings suggest caffeine restrictions in migraineurs may not be necessary.

METHODOLOGY:

• The secondary analysis of a prospective cohort study on sleep in adults with episodic migraine (with or without aura) included a group of 97 people (median age, 31 years; 82% White) with an average of 5.0 ± 3.6  days per month at baseline.
• Participants provided sociodemographic information, medical history, habitual caffeinated beverage consumption, alcohol intake, and lifestyle and psychosocial factors and completed the Center for Epidemiologic Studies- scale, the Perceived Stress Scale, and the Pittsburgh Sleep Quality Index.
• Additionally, they completed twice-daily electronic diaries for the subsequent 6 weeks, reporting headache activity and the use of medications to treat the headache.

TAKEAWAY:

• A total of 67% of participants reported one to two servings of caffeinated beverages per day, 12% reported three to four servings per day, and 21% reported no habitual caffeine consumption.
• After adjusting for age, sex, oral  use, and other confounders, mean headache frequency was similar among groups (7.1 days for no caffeine, 7.4 days for one to two servings, and 5.9 days for three to four servings).
• Similarly, adjusted mean headache duration did not differ across levels of caffeinated beverage intake (8.6 hours for no caffeine, 8.5 hours for one to two servings, and 8.8 hours for three to four servings).
• Adjusted mean headache intensity also did not differ among groups.

IN PRACTICE:

“Our findings do not support a recommendation for people with episodic migraine to avoid habitual caffeinated beverage intake,” the authors wrote. However, they noted that habitual caffeine intake may affect systems involved in pain modulation via adenosine signaling. «Therefore, it is possible that habitual caffeine use in those with migraine does not significantly alter adenosine signaling, but significant changes above or below usual consumption may serve as a trigger or contribute to lowering the threshold for an attack to occur along with other triggers,» they added.

SOURCE:

Suzanne M. Bertisch, MD, MPH, assistant professor of medicine, Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, was the senior and corresponding author of the study. It was published online in Headache.

LIMITATIONS:

Serving size was not standardized, and there was no information on the type of caffeinated beverage consumed or about other sources of caffeine. Moreover, the population consisted of relatively healthy participants with episodic migraine and generally low levels of habitual caffeinated beverage intake, which limited the statistical power to detect an association between migraine frequency, duration, and intensity with higher levels of caffeine intake.

DISCLOSURES:

The study was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, and the Harvard Catalyst/Harvard Clinical and Translational Science Center. Dr. Bertisch has done consulting work with Idorsia and ResMed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Greater adherence to a plant-based dietary pattern was associated with a lower risk of developing type 2 diabetes (T2D) among middle-aged US adults. Greater intake of healthful plant foods, rather than lower intake of non-red meat animal foods, was the main factor underlying the inverse associations.

METHODOLOGY:

• The study population was 11,965 adults aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study who didn›t have diabetes at baseline and who completed food-frequency questionnaires.
• Plant-based diet adherence was classified overall with the plant-based diet index (PDI) and also with higher healthful PDI (hPDI) and higher unhealthful PDI (uPDI) indexes.

TAKEAWAY:

• Mean daily total plant and animal food intakes for the highest quintile (5) were 15.1 and 3.4 servings per day, respectively, whereas average consumption for the lowest quintile (1) was 9.9 and 5.8 servings per day, respectively.
• During a median 22 years’ follow-up, 35% (n = 4208) of the participants developed T2D.
• After controlling for age, sex, race center, energy intake, education, income, smoking, alcohol intake, physical activity, and margarine intake, those in PDI quintile 5 had a significantly lower risk of developing T2D than in quintile 1 (hazard ratio, 0.89; P = .01).
• As a continuous score, each 10-point higher PDI score was associated with a significant 6% lower risk for T2D (P = .01).
• Higher hPDI scores were also inversely associated with T2D risk (hazard ratio, 0.85 for quintiles 5 vs 1; P < .001), and (0.90 per each 10 units higher; P < .001).
• Higher uPDI scores were not significantly associated with diabetes risk, regardless of adjustments (P > .05).
• Associations between plant-based diet scores and diabetes did not differ by sex, age, race, or body mass index (BMI) after accounting for multiple comparisons (all P interaction > .05).
• Further adjustment for BMI attenuated the associations between overall and healthy plant-based diets and diabetes risk, suggesting that lower adiposity may partly explain the favorable association.

IN PRACTICE:

“Emphasizing plant foods may be an effective dietary strategy to delay or prevent the onset of diabetes.”

SOURCE:

The study conducted by Valerie K. Sullivan, PhD, RD, of the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, and colleagues was published online in Diabetes Care.

LIMITATIONS:

The limitations were self-reported dietary intake, diets assessed decades ago, possible food misclassification, possible selection bias, and residual confounding.

DISCLOSURES:

The ARIC study was funded by the US National Institutes of Health. The authors had no further disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Greater adherence to a plant-based dietary pattern was associated with a lower risk of developing type 2 diabetes (T2D) among middle-aged US adults. Greater intake of healthful plant foods, rather than lower intake of non-red meat animal foods, was the main factor underlying the inverse associations.

METHODOLOGY:

• The study population was 11,965 adults aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study who didn›t have diabetes at baseline and who completed food-frequency questionnaires.
• Plant-based diet adherence was classified overall with the plant-based diet index (PDI) and also with higher healthful PDI (hPDI) and higher unhealthful PDI (uPDI) indexes.

TAKEAWAY:

• Mean daily total plant and animal food intakes for the highest quintile (5) were 15.1 and 3.4 servings per day, respectively, whereas average consumption for the lowest quintile (1) was 9.9 and 5.8 servings per day, respectively.
• During a median 22 years’ follow-up, 35% (n = 4208) of the participants developed T2D.
• After controlling for age, sex, race center, energy intake, education, income, smoking, alcohol intake, physical activity, and margarine intake, those in PDI quintile 5 had a significantly lower risk of developing T2D than in quintile 1 (hazard ratio, 0.89; P = .01).
• As a continuous score, each 10-point higher PDI score was associated with a significant 6% lower risk for T2D (P = .01).
• Higher hPDI scores were also inversely associated with T2D risk (hazard ratio, 0.85 for quintiles 5 vs 1; P < .001), and (0.90 per each 10 units higher; P < .001).
• Higher uPDI scores were not significantly associated with diabetes risk, regardless of adjustments (P > .05).
• Associations between plant-based diet scores and diabetes did not differ by sex, age, race, or body mass index (BMI) after accounting for multiple comparisons (all P interaction > .05).
• Further adjustment for BMI attenuated the associations between overall and healthy plant-based diets and diabetes risk, suggesting that lower adiposity may partly explain the favorable association.

IN PRACTICE:

“Emphasizing plant foods may be an effective dietary strategy to delay or prevent the onset of diabetes.”

SOURCE:

The study conducted by Valerie K. Sullivan, PhD, RD, of the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, and colleagues was published online in Diabetes Care.

LIMITATIONS:

The limitations were self-reported dietary intake, diets assessed decades ago, possible food misclassification, possible selection bias, and residual confounding.

DISCLOSURES:

The ARIC study was funded by the US National Institutes of Health. The authors had no further disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Greater adherence to a plant-based dietary pattern was associated with a lower risk of developing type 2 diabetes (T2D) among middle-aged US adults. Greater intake of healthful plant foods, rather than lower intake of non-red meat animal foods, was the main factor underlying the inverse associations.

METHODOLOGY:

• The study population was 11,965 adults aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study who didn›t have diabetes at baseline and who completed food-frequency questionnaires.
• Plant-based diet adherence was classified overall with the plant-based diet index (PDI) and also with higher healthful PDI (hPDI) and higher unhealthful PDI (uPDI) indexes.

TAKEAWAY:

• Mean daily total plant and animal food intakes for the highest quintile (5) were 15.1 and 3.4 servings per day, respectively, whereas average consumption for the lowest quintile (1) was 9.9 and 5.8 servings per day, respectively.
• During a median 22 years’ follow-up, 35% (n = 4208) of the participants developed T2D.
• After controlling for age, sex, race center, energy intake, education, income, smoking, alcohol intake, physical activity, and margarine intake, those in PDI quintile 5 had a significantly lower risk of developing T2D than in quintile 1 (hazard ratio, 0.89; P = .01).
• As a continuous score, each 10-point higher PDI score was associated with a significant 6% lower risk for T2D (P = .01).
• Higher hPDI scores were also inversely associated with T2D risk (hazard ratio, 0.85 for quintiles 5 vs 1; P < .001), and (0.90 per each 10 units higher; P < .001).
• Higher uPDI scores were not significantly associated with diabetes risk, regardless of adjustments (P > .05).
• Associations between plant-based diet scores and diabetes did not differ by sex, age, race, or body mass index (BMI) after accounting for multiple comparisons (all P interaction > .05).
• Further adjustment for BMI attenuated the associations between overall and healthy plant-based diets and diabetes risk, suggesting that lower adiposity may partly explain the favorable association.

IN PRACTICE:

“Emphasizing plant foods may be an effective dietary strategy to delay or prevent the onset of diabetes.”

SOURCE:

The study conducted by Valerie K. Sullivan, PhD, RD, of the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, and colleagues was published online in Diabetes Care.

LIMITATIONS:

The limitations were self-reported dietary intake, diets assessed decades ago, possible food misclassification, possible selection bias, and residual confounding.

DISCLOSURES:

The ARIC study was funded by the US National Institutes of Health. The authors had no further disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved omalizumab (Xolair, Genentech) for reducing allergic reactions to foods in adults and most children. The drug is meant to be taken regularly by patients with food allergies to reduce the risk for reactions, including anaphylaxis, in case of accidental exposure to one or more allergens. The injection is not approved for emergency treatment of an allergic reaction.

Omalizumab first was approved for persistent allergic asthma in 2003. It also is approved for chronic spontaneous urticaria and chronic rhinosinusitis with nasal polyps. 

The new indication for immunoglobulin E–mediated food allergy in adults and children aged 1 year or older makes omalizumab the first drug approved to mitigate allergic reactions to more than one food, the FDA said. Peanut-allergen powder (Palforzia) can reduce reactions to peanut, but its benefits are limited to that allergy.

“While it will not eliminate food allergies or allow patients to consume food allergens freely, its repeated use will help reduce the health impact if accidental exposure occurs,” said Kelly Stone, MD, PhD, associate director of the division of pulmonology, allergy, and critical care in the FDA’s Center for Drug Evaluation and Research, in a news release. 

The safety and efficacy of the monoclonal antibody in reducing allergic reactions was studied in a double-blind, placebo-controlled study of 168 children and adults who were allergic to peanut and at least two other foods, including milk, egg, wheat, cashew, hazelnut, or walnut. Patients received omalizumab or placebo for 16-20 weeks. At the end of the study, patients consumed peanut protein (equivalent to 2.5 peanuts). Of those who received the drug, 68% were able to consume peanut without moderate or severe allergic symptoms, versus 6% in the placebo group.

More patients who received the medication also avoided moderate or severe reactions to cashews (42% vs 3%), milk (66% vs 11%), and eggs (67% vs 0%). 

The most common side effects of omalizumab included injection site reactions and fever. The drug’s label includes warnings and precautions about anaphylaxis, cancer, fever, joint pain, rash, parasitic (worm) infection, and abnormal laboratory tests. Omalizumab comes with a boxed warning for anaphylaxis and should be started only in a healthcare setting equipped to manage anaphylaxis, according to the FDA.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved omalizumab (Xolair, Genentech) for reducing allergic reactions to foods in adults and most children. The drug is meant to be taken regularly by patients with food allergies to reduce the risk for reactions, including anaphylaxis, in case of accidental exposure to one or more allergens. The injection is not approved for emergency treatment of an allergic reaction.

Omalizumab first was approved for persistent allergic asthma in 2003. It also is approved for chronic spontaneous urticaria and chronic rhinosinusitis with nasal polyps. 

The new indication for immunoglobulin E–mediated food allergy in adults and children aged 1 year or older makes omalizumab the first drug approved to mitigate allergic reactions to more than one food, the FDA said. Peanut-allergen powder (Palforzia) can reduce reactions to peanut, but its benefits are limited to that allergy.

“While it will not eliminate food allergies or allow patients to consume food allergens freely, its repeated use will help reduce the health impact if accidental exposure occurs,” said Kelly Stone, MD, PhD, associate director of the division of pulmonology, allergy, and critical care in the FDA’s Center for Drug Evaluation and Research, in a news release. 

The safety and efficacy of the monoclonal antibody in reducing allergic reactions was studied in a double-blind, placebo-controlled study of 168 children and adults who were allergic to peanut and at least two other foods, including milk, egg, wheat, cashew, hazelnut, or walnut. Patients received omalizumab or placebo for 16-20 weeks. At the end of the study, patients consumed peanut protein (equivalent to 2.5 peanuts). Of those who received the drug, 68% were able to consume peanut without moderate or severe allergic symptoms, versus 6% in the placebo group.

More patients who received the medication also avoided moderate or severe reactions to cashews (42% vs 3%), milk (66% vs 11%), and eggs (67% vs 0%). 

The most common side effects of omalizumab included injection site reactions and fever. The drug’s label includes warnings and precautions about anaphylaxis, cancer, fever, joint pain, rash, parasitic (worm) infection, and abnormal laboratory tests. Omalizumab comes with a boxed warning for anaphylaxis and should be started only in a healthcare setting equipped to manage anaphylaxis, according to the FDA.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved omalizumab (Xolair, Genentech) for reducing allergic reactions to foods in adults and most children. The drug is meant to be taken regularly by patients with food allergies to reduce the risk for reactions, including anaphylaxis, in case of accidental exposure to one or more allergens. The injection is not approved for emergency treatment of an allergic reaction.

Omalizumab first was approved for persistent allergic asthma in 2003. It also is approved for chronic spontaneous urticaria and chronic rhinosinusitis with nasal polyps. 

The new indication for immunoglobulin E–mediated food allergy in adults and children aged 1 year or older makes omalizumab the first drug approved to mitigate allergic reactions to more than one food, the FDA said. Peanut-allergen powder (Palforzia) can reduce reactions to peanut, but its benefits are limited to that allergy.

“While it will not eliminate food allergies or allow patients to consume food allergens freely, its repeated use will help reduce the health impact if accidental exposure occurs,” said Kelly Stone, MD, PhD, associate director of the division of pulmonology, allergy, and critical care in the FDA’s Center for Drug Evaluation and Research, in a news release. 

The safety and efficacy of the monoclonal antibody in reducing allergic reactions was studied in a double-blind, placebo-controlled study of 168 children and adults who were allergic to peanut and at least two other foods, including milk, egg, wheat, cashew, hazelnut, or walnut. Patients received omalizumab or placebo for 16-20 weeks. At the end of the study, patients consumed peanut protein (equivalent to 2.5 peanuts). Of those who received the drug, 68% were able to consume peanut without moderate or severe allergic symptoms, versus 6% in the placebo group.

More patients who received the medication also avoided moderate or severe reactions to cashews (42% vs 3%), milk (66% vs 11%), and eggs (67% vs 0%). 

The most common side effects of omalizumab included injection site reactions and fever. The drug’s label includes warnings and precautions about anaphylaxis, cancer, fever, joint pain, rash, parasitic (worm) infection, and abnormal laboratory tests. Omalizumab comes with a boxed warning for anaphylaxis and should be started only in a healthcare setting equipped to manage anaphylaxis, according to the FDA.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with stages I-III colorectal cancer (CRC) who are cancer-free 5 years after surgery, the incidence of late recurrence or metachronous disease after 5 years is low and has decreased over time, new data showed.

METHODOLOGY:

• Recent treatment advances in CRC have reduced the likelihood that patients with nonmetastatic disease will recur or develop a second primary cancer more than 6 months after the first. Although late recurrences and metachronous CRC remain infrequent, it’s not clear if patients might benefit from longer term surveillance.
• To investigate whether extending surveillance beyond the recommended 5 years is beneficial, researchers assessed the incidence of late recurrence, metachronous CRC, and second primary cancers 5 years after surgical resection with curative intent.
• The researchers identified patients with stages I-III CRC, under age 80 years, from Danish healthcare registries who underwent surgical resection between January 2004 and December 2013.
• A total of 8883 patients were followed from 5 years after primary surgery until the date of recurrence, metachronous CRC, or second non-CRC primary cancer.

TAKEAWAY:

• Between 5 and 10 years after surgery, 370 survivors developed late recurrence (4.16%), 270 developed metachronous disease (3.0%), and 635 were diagnosed with a second primary cancer (7.15%).
• During 2009-2013 and 2004-2008, the risk for late recurrence decreased by 48% (5.6% vs 2.9%; subdistribution hazard ratio [sHR], 0.52) and the risk for metachronous disease decreased by 50% (4.1% vs 2.1%; sHR, 0.50).
• During the same timeframe, the risk for second non-CRC primary cancer remained unchanged (7.1% vs 7.1%; sHR, 0.98).
• Compared with patients diagnosed with late recurrences (46%), 5-year overall survival was higher for patients with metachronous CRC (72%; adjusted HR, 0.37) and slightly higher for those with second primary cancers (48%; adjusted HR, 0.78).

IN PRACTICE:

Because the incidences of late recurrence and metachronous CRC are low and decreased between 2004 and 2013, the data do not support extending CRC-specific surveillance beyond 5 years, the authors concluded. “Symptoms or suspicion of a cancer occurring 5-10 years from primary CRC treatment, is more likely to represent a non-CRC cancer (7.1%).”

SOURCE:

This study, led by Jesper Nors from Aarhus University Hospital, Aarhus, Denmark, was published on February 7, 2024, in the International Journal of Cancer.

LIMITATIONS:

Misclassification of a late recurrence or metachronous CRC could have affected the findings.

DISCLOSURES:

This work was funded by Institute of Clinical Medicine, Aarhus University, Denmark, Novo Nordisk Foundation, Innovation Fund Denmark, and the Danish Cancer Society. The authors reported no conflict of interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with stages I-III colorectal cancer (CRC) who are cancer-free 5 years after surgery, the incidence of late recurrence or metachronous disease after 5 years is low and has decreased over time, new data showed.

METHODOLOGY:

• Recent treatment advances in CRC have reduced the likelihood that patients with nonmetastatic disease will recur or develop a second primary cancer more than 6 months after the first. Although late recurrences and metachronous CRC remain infrequent, it’s not clear if patients might benefit from longer term surveillance.
• To investigate whether extending surveillance beyond the recommended 5 years is beneficial, researchers assessed the incidence of late recurrence, metachronous CRC, and second primary cancers 5 years after surgical resection with curative intent.
• The researchers identified patients with stages I-III CRC, under age 80 years, from Danish healthcare registries who underwent surgical resection between January 2004 and December 2013.
• A total of 8883 patients were followed from 5 years after primary surgery until the date of recurrence, metachronous CRC, or second non-CRC primary cancer.

TAKEAWAY:

• Between 5 and 10 years after surgery, 370 survivors developed late recurrence (4.16%), 270 developed metachronous disease (3.0%), and 635 were diagnosed with a second primary cancer (7.15%).
• During 2009-2013 and 2004-2008, the risk for late recurrence decreased by 48% (5.6% vs 2.9%; subdistribution hazard ratio [sHR], 0.52) and the risk for metachronous disease decreased by 50% (4.1% vs 2.1%; sHR, 0.50).
• During the same timeframe, the risk for second non-CRC primary cancer remained unchanged (7.1% vs 7.1%; sHR, 0.98).
• Compared with patients diagnosed with late recurrences (46%), 5-year overall survival was higher for patients with metachronous CRC (72%; adjusted HR, 0.37) and slightly higher for those with second primary cancers (48%; adjusted HR, 0.78).

IN PRACTICE:

Because the incidences of late recurrence and metachronous CRC are low and decreased between 2004 and 2013, the data do not support extending CRC-specific surveillance beyond 5 years, the authors concluded. “Symptoms or suspicion of a cancer occurring 5-10 years from primary CRC treatment, is more likely to represent a non-CRC cancer (7.1%).”

SOURCE:

This study, led by Jesper Nors from Aarhus University Hospital, Aarhus, Denmark, was published on February 7, 2024, in the International Journal of Cancer.

LIMITATIONS:

Misclassification of a late recurrence or metachronous CRC could have affected the findings.

DISCLOSURES:

This work was funded by Institute of Clinical Medicine, Aarhus University, Denmark, Novo Nordisk Foundation, Innovation Fund Denmark, and the Danish Cancer Society. The authors reported no conflict of interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with stages I-III colorectal cancer (CRC) who are cancer-free 5 years after surgery, the incidence of late recurrence or metachronous disease after 5 years is low and has decreased over time, new data showed.

METHODOLOGY:

• Recent treatment advances in CRC have reduced the likelihood that patients with nonmetastatic disease will recur or develop a second primary cancer more than 6 months after the first. Although late recurrences and metachronous CRC remain infrequent, it’s not clear if patients might benefit from longer term surveillance.
• To investigate whether extending surveillance beyond the recommended 5 years is beneficial, researchers assessed the incidence of late recurrence, metachronous CRC, and second primary cancers 5 years after surgical resection with curative intent.
• The researchers identified patients with stages I-III CRC, under age 80 years, from Danish healthcare registries who underwent surgical resection between January 2004 and December 2013.
• A total of 8883 patients were followed from 5 years after primary surgery until the date of recurrence, metachronous CRC, or second non-CRC primary cancer.

TAKEAWAY:

• Between 5 and 10 years after surgery, 370 survivors developed late recurrence (4.16%), 270 developed metachronous disease (3.0%), and 635 were diagnosed with a second primary cancer (7.15%).
• During 2009-2013 and 2004-2008, the risk for late recurrence decreased by 48% (5.6% vs 2.9%; subdistribution hazard ratio [sHR], 0.52) and the risk for metachronous disease decreased by 50% (4.1% vs 2.1%; sHR, 0.50).
• During the same timeframe, the risk for second non-CRC primary cancer remained unchanged (7.1% vs 7.1%; sHR, 0.98).
• Compared with patients diagnosed with late recurrences (46%), 5-year overall survival was higher for patients with metachronous CRC (72%; adjusted HR, 0.37) and slightly higher for those with second primary cancers (48%; adjusted HR, 0.78).

IN PRACTICE:

Because the incidences of late recurrence and metachronous CRC are low and decreased between 2004 and 2013, the data do not support extending CRC-specific surveillance beyond 5 years, the authors concluded. “Symptoms or suspicion of a cancer occurring 5-10 years from primary CRC treatment, is more likely to represent a non-CRC cancer (7.1%).”

SOURCE:

This study, led by Jesper Nors from Aarhus University Hospital, Aarhus, Denmark, was published on February 7, 2024, in the International Journal of Cancer.

LIMITATIONS:

Misclassification of a late recurrence or metachronous CRC could have affected the findings.

DISCLOSURES:

This work was funded by Institute of Clinical Medicine, Aarhus University, Denmark, Novo Nordisk Foundation, Innovation Fund Denmark, and the Danish Cancer Society. The authors reported no conflict of interests.

A version of this article appeared on Medscape.com.

Cognitive impairment in some US veterans may be due to treatable hepatic encephalopathy (HE) rather than dementia, new research suggested.

From 5%-10% of veterans diagnosed with dementia had possible undiagnosed cirrhosis, implicating HE as a contributor to cognitive impairment, found the study by Jasmohan S. Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Virginia, and colleagues.

The research was prompted, in part, by an earlier case study by Dr. Bajaj and colleagues that showed that two older men diagnosed with dementia and Parkinson’s disease actually had HE, meaning their symptoms were due to advanced but treatable liver disease.

“Once they were properly diagnosed, whatever had been considered dementia was gone,” Dr. Bajaj said. “The spouse of one man said, ‘My husband is a different person now.’ It’s not that clinicians don’t know how to treat HE; the problem was that they did not suspect it.”

Among veterans with cirrhosis, concomitant dementia is common and is difficult to distinguish from HE, but the extent to which patients with dementia also have undiagnosed cirrhosis and HE is unknown, the authors of the current study wrote. “Undiagnosed cirrhosis among veterans with dementia could raise the possibility that part of their cognitive impairment may be due to reversible HE,” they added.

To investigate, the researchers examined the prevalence and risk factors of undiagnosed cirrhosis — and therefore, possible HE — among US veterans.

The study was published online in JAMA Network Open.
 

Dementia or Cirrhosis?

Using the VHA Corporate Data Warehouse, researchers analyzed medical records of 177,422 US veterans diagnosed with dementia but not cirrhosis between 2009 and 2019 and with sufficient laboratory test results to calculate their Fibrosis-4 (FIB-4) scores. The mean age was 78.35 years, 97.1% were men, and 80.7% were White individuals.

The FIB-4 score for each patient was calculated using the most recent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels or values and platelet values that were closest to the index date during the two years after the index dementia date.

Age is in the numerator of the FIB-4 score calculation; hence, higher age could lead to an erroneously high FIB-4 score, the authors noted. Therefore, for patients older than 65 years, the researchers entered 65 years as an input variable, rather than the actual age.

A FIB-4 score > 2.67 was suggestive of advanced fibrosis, whereas a score > 3.25 was suggestive of cirrhosis. 

A total of 18,390 (10.3%) veterans had a FIB-4 score > 2.67, and 9373 (5.3%) had a FIB-4 score > 3.25.

In multivariable logistic regression models, a FIB-4 score > 3.25 was associated with older age (odds ratio [OR], 1.07), male sex (OR, 1.43), congestive heart failure (OR, 1.48), viral hepatitis (OR, 1.79), an Alcohol Use Disorders Identification Test score showing problem drinking (OR, 1.56), and chronic kidney disease (OR, 1.11).

In contrast, a FIB-4 score > 3.25 was inversely associated with the White race (OR, 0.79), diabetes (OR, 0.78), hyperlipidemia (OR, 0.84), stroke (OR, 0.85), tobacco use disorder (OR, 0.78), and rural residence (OR, 0.92).

Similar findings were associated with the FIB-4 greater than 2.67 threshold.

In a follow-up validation study among 89 veterans diagnosed with dementia at a single center, the researchers found similar results: 4.4%-11.2% of participants had high FIB-4 scores, suggestive of HE.

After investigating further, they concluded that 5% of patients in that cohort had reasons other than cirrhosis for their high FIB-4 scores. The remaining patients (95%) had evidence of cirrhosis, had risk factors, and/or had no other explanation for their high FIB-4 scores.

“The combination of high FIB-4 scores and other risk factors for liver disease in patients with dementia raises the possibility that reversible HE could be a factor associated with cognitive impairment,” the authors wrote. “These findings highlight the potential to enhance cognitive function and quality of life by increasing awareness of risk factors and diagnostic indicators of advanced liver disease that may be associated with HE as a factor or as a differential diagnosis of dementia among clinicians other than liver specialists.”
 

FIB-4 Screening Advised

“An elderly patient with cirrhosis used to be an oxymoron, because we never used to have people who lived this long or were diagnosed this late with cirrhosis,” Dr. Bajaj told this news organization. “It’s a good problem to have because people are now living longer, but it also means that we need to have every single person who is taking care of patients with what is deemed to be dementia know that the patient could also have an element of encephalopathy.”

Increased awareness is important because, unlike dementia, encephalopathy is very easily treated, Dr. Bajaj said. “The biggest, easiest, correctable cause is to figure out if they have severe liver disease, and if that’s the case, your friendly neighborhood gastroenterologist is waiting for you,” he added.

The finding that cirrhosis was present in 95% of patients in the validation cohort is “very impressive, as they had excluded from the consideration all those with obvious cirrhosis before the FIB-4 was done,” said William Carey, MD, acting hepatology section head in the Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic’s Digestive Disease Institute in Ohio. “This validates FIB-4 as a powerful tool for cirrhosis case-finding.” 

Ordering a FIB-4 “is within the skill set of every healthcare provider,” Dr. Carey, who was not involved in the study, told this news organization. “Patients with altered mental status, including suspected or proven dementia, should be screened for possible cirrhosis, as future management will change. Those with elevated FIB-4 results should also be tested for possible HE and treated if it is present.”

The study was partly funded by VA Merit Review grants to Dr. Bajaj. Dr. Bajaj reported receiving grants from Bausch, Grifols, Sequana, and Mallinckrodt outside the submitted work. Dr. Carey reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Cognitive impairment in some US veterans may be due to treatable hepatic encephalopathy (HE) rather than dementia, new research suggested.

From 5%-10% of veterans diagnosed with dementia had possible undiagnosed cirrhosis, implicating HE as a contributor to cognitive impairment, found the study by Jasmohan S. Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Virginia, and colleagues.

The research was prompted, in part, by an earlier case study by Dr. Bajaj and colleagues that showed that two older men diagnosed with dementia and Parkinson’s disease actually had HE, meaning their symptoms were due to advanced but treatable liver disease.

“Once they were properly diagnosed, whatever had been considered dementia was gone,” Dr. Bajaj said. “The spouse of one man said, ‘My husband is a different person now.’ It’s not that clinicians don’t know how to treat HE; the problem was that they did not suspect it.”

Among veterans with cirrhosis, concomitant dementia is common and is difficult to distinguish from HE, but the extent to which patients with dementia also have undiagnosed cirrhosis and HE is unknown, the authors of the current study wrote. “Undiagnosed cirrhosis among veterans with dementia could raise the possibility that part of their cognitive impairment may be due to reversible HE,” they added.

To investigate, the researchers examined the prevalence and risk factors of undiagnosed cirrhosis — and therefore, possible HE — among US veterans.

The study was published online in JAMA Network Open.
 

Dementia or Cirrhosis?

Using the VHA Corporate Data Warehouse, researchers analyzed medical records of 177,422 US veterans diagnosed with dementia but not cirrhosis between 2009 and 2019 and with sufficient laboratory test results to calculate their Fibrosis-4 (FIB-4) scores. The mean age was 78.35 years, 97.1% were men, and 80.7% were White individuals.

The FIB-4 score for each patient was calculated using the most recent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels or values and platelet values that were closest to the index date during the two years after the index dementia date.

Age is in the numerator of the FIB-4 score calculation; hence, higher age could lead to an erroneously high FIB-4 score, the authors noted. Therefore, for patients older than 65 years, the researchers entered 65 years as an input variable, rather than the actual age.

A FIB-4 score > 2.67 was suggestive of advanced fibrosis, whereas a score > 3.25 was suggestive of cirrhosis. 

A total of 18,390 (10.3%) veterans had a FIB-4 score > 2.67, and 9373 (5.3%) had a FIB-4 score > 3.25.

In multivariable logistic regression models, a FIB-4 score > 3.25 was associated with older age (odds ratio [OR], 1.07), male sex (OR, 1.43), congestive heart failure (OR, 1.48), viral hepatitis (OR, 1.79), an Alcohol Use Disorders Identification Test score showing problem drinking (OR, 1.56), and chronic kidney disease (OR, 1.11).

In contrast, a FIB-4 score > 3.25 was inversely associated with the White race (OR, 0.79), diabetes (OR, 0.78), hyperlipidemia (OR, 0.84), stroke (OR, 0.85), tobacco use disorder (OR, 0.78), and rural residence (OR, 0.92).

Similar findings were associated with the FIB-4 greater than 2.67 threshold.

In a follow-up validation study among 89 veterans diagnosed with dementia at a single center, the researchers found similar results: 4.4%-11.2% of participants had high FIB-4 scores, suggestive of HE.

After investigating further, they concluded that 5% of patients in that cohort had reasons other than cirrhosis for their high FIB-4 scores. The remaining patients (95%) had evidence of cirrhosis, had risk factors, and/or had no other explanation for their high FIB-4 scores.

“The combination of high FIB-4 scores and other risk factors for liver disease in patients with dementia raises the possibility that reversible HE could be a factor associated with cognitive impairment,” the authors wrote. “These findings highlight the potential to enhance cognitive function and quality of life by increasing awareness of risk factors and diagnostic indicators of advanced liver disease that may be associated with HE as a factor or as a differential diagnosis of dementia among clinicians other than liver specialists.”
 

FIB-4 Screening Advised

“An elderly patient with cirrhosis used to be an oxymoron, because we never used to have people who lived this long or were diagnosed this late with cirrhosis,” Dr. Bajaj told this news organization. “It’s a good problem to have because people are now living longer, but it also means that we need to have every single person who is taking care of patients with what is deemed to be dementia know that the patient could also have an element of encephalopathy.”

Increased awareness is important because, unlike dementia, encephalopathy is very easily treated, Dr. Bajaj said. “The biggest, easiest, correctable cause is to figure out if they have severe liver disease, and if that’s the case, your friendly neighborhood gastroenterologist is waiting for you,” he added.

The finding that cirrhosis was present in 95% of patients in the validation cohort is “very impressive, as they had excluded from the consideration all those with obvious cirrhosis before the FIB-4 was done,” said William Carey, MD, acting hepatology section head in the Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic’s Digestive Disease Institute in Ohio. “This validates FIB-4 as a powerful tool for cirrhosis case-finding.” 

Ordering a FIB-4 “is within the skill set of every healthcare provider,” Dr. Carey, who was not involved in the study, told this news organization. “Patients with altered mental status, including suspected or proven dementia, should be screened for possible cirrhosis, as future management will change. Those with elevated FIB-4 results should also be tested for possible HE and treated if it is present.”

The study was partly funded by VA Merit Review grants to Dr. Bajaj. Dr. Bajaj reported receiving grants from Bausch, Grifols, Sequana, and Mallinckrodt outside the submitted work. Dr. Carey reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Cognitive impairment in some US veterans may be due to treatable hepatic encephalopathy (HE) rather than dementia, new research suggested.

From 5%-10% of veterans diagnosed with dementia had possible undiagnosed cirrhosis, implicating HE as a contributor to cognitive impairment, found the study by Jasmohan S. Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Virginia, and colleagues.

The research was prompted, in part, by an earlier case study by Dr. Bajaj and colleagues that showed that two older men diagnosed with dementia and Parkinson’s disease actually had HE, meaning their symptoms were due to advanced but treatable liver disease.

“Once they were properly diagnosed, whatever had been considered dementia was gone,” Dr. Bajaj said. “The spouse of one man said, ‘My husband is a different person now.’ It’s not that clinicians don’t know how to treat HE; the problem was that they did not suspect it.”

Among veterans with cirrhosis, concomitant dementia is common and is difficult to distinguish from HE, but the extent to which patients with dementia also have undiagnosed cirrhosis and HE is unknown, the authors of the current study wrote. “Undiagnosed cirrhosis among veterans with dementia could raise the possibility that part of their cognitive impairment may be due to reversible HE,” they added.

To investigate, the researchers examined the prevalence and risk factors of undiagnosed cirrhosis — and therefore, possible HE — among US veterans.

The study was published online in JAMA Network Open.
 

Dementia or Cirrhosis?

Using the VHA Corporate Data Warehouse, researchers analyzed medical records of 177,422 US veterans diagnosed with dementia but not cirrhosis between 2009 and 2019 and with sufficient laboratory test results to calculate their Fibrosis-4 (FIB-4) scores. The mean age was 78.35 years, 97.1% were men, and 80.7% were White individuals.

The FIB-4 score for each patient was calculated using the most recent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels or values and platelet values that were closest to the index date during the two years after the index dementia date.

Age is in the numerator of the FIB-4 score calculation; hence, higher age could lead to an erroneously high FIB-4 score, the authors noted. Therefore, for patients older than 65 years, the researchers entered 65 years as an input variable, rather than the actual age.

A FIB-4 score > 2.67 was suggestive of advanced fibrosis, whereas a score > 3.25 was suggestive of cirrhosis. 

A total of 18,390 (10.3%) veterans had a FIB-4 score > 2.67, and 9373 (5.3%) had a FIB-4 score > 3.25.

In multivariable logistic regression models, a FIB-4 score > 3.25 was associated with older age (odds ratio [OR], 1.07), male sex (OR, 1.43), congestive heart failure (OR, 1.48), viral hepatitis (OR, 1.79), an Alcohol Use Disorders Identification Test score showing problem drinking (OR, 1.56), and chronic kidney disease (OR, 1.11).

In contrast, a FIB-4 score > 3.25 was inversely associated with the White race (OR, 0.79), diabetes (OR, 0.78), hyperlipidemia (OR, 0.84), stroke (OR, 0.85), tobacco use disorder (OR, 0.78), and rural residence (OR, 0.92).

Similar findings were associated with the FIB-4 greater than 2.67 threshold.

In a follow-up validation study among 89 veterans diagnosed with dementia at a single center, the researchers found similar results: 4.4%-11.2% of participants had high FIB-4 scores, suggestive of HE.

After investigating further, they concluded that 5% of patients in that cohort had reasons other than cirrhosis for their high FIB-4 scores. The remaining patients (95%) had evidence of cirrhosis, had risk factors, and/or had no other explanation for their high FIB-4 scores.

“The combination of high FIB-4 scores and other risk factors for liver disease in patients with dementia raises the possibility that reversible HE could be a factor associated with cognitive impairment,” the authors wrote. “These findings highlight the potential to enhance cognitive function and quality of life by increasing awareness of risk factors and diagnostic indicators of advanced liver disease that may be associated with HE as a factor or as a differential diagnosis of dementia among clinicians other than liver specialists.”
 

FIB-4 Screening Advised

“An elderly patient with cirrhosis used to be an oxymoron, because we never used to have people who lived this long or were diagnosed this late with cirrhosis,” Dr. Bajaj told this news organization. “It’s a good problem to have because people are now living longer, but it also means that we need to have every single person who is taking care of patients with what is deemed to be dementia know that the patient could also have an element of encephalopathy.”

Increased awareness is important because, unlike dementia, encephalopathy is very easily treated, Dr. Bajaj said. “The biggest, easiest, correctable cause is to figure out if they have severe liver disease, and if that’s the case, your friendly neighborhood gastroenterologist is waiting for you,” he added.

The finding that cirrhosis was present in 95% of patients in the validation cohort is “very impressive, as they had excluded from the consideration all those with obvious cirrhosis before the FIB-4 was done,” said William Carey, MD, acting hepatology section head in the Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic’s Digestive Disease Institute in Ohio. “This validates FIB-4 as a powerful tool for cirrhosis case-finding.” 

Ordering a FIB-4 “is within the skill set of every healthcare provider,” Dr. Carey, who was not involved in the study, told this news organization. “Patients with altered mental status, including suspected or proven dementia, should be screened for possible cirrhosis, as future management will change. Those with elevated FIB-4 results should also be tested for possible HE and treated if it is present.”

The study was partly funded by VA Merit Review grants to Dr. Bajaj. Dr. Bajaj reported receiving grants from Bausch, Grifols, Sequana, and Mallinckrodt outside the submitted work. Dr. Carey reported no relevant disclosures.

A version of this article appeared on Medscape.com.