Key clinical point: High diastolic whole blood viscosity (WBV) may serve as a new independent factor associated with extrahepatic metastasis and poor survival in patients with hepatocellular carcinoma (HCC).

Main finding: After adjusting for confounding variables, high diastolic WBV was independently associated with extrahepatic metastasis (adjusted odds ratio, 23.41; P < .001) and poor survival (adjusted hazard ratio, 3.81; P < .001) and significantly predicted extrahepatic metastasis at an optimal cutoff of 16 cP (area under the receiver operating characteristic curve, 0.768; P < .001).

Study details: Findings are from a pilot retrospective study including 181 patients with HCC, of which 148 were treatment-naïve having preserved liver function and 33 received nivolumab.

Disclosures: The study was sponsored by Young Medical Scientist Research Grant through the Daewoong Foundation and the Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea. The authors did not declare any conflict of interests.

Source: Han JW et al. PLoS ONE. 2021 Dec 2. doi: 10.1371/journal.pone.0260311.

Key clinical point: High diastolic whole blood viscosity (WBV) may serve as a new independent factor associated with extrahepatic metastasis and poor survival in patients with hepatocellular carcinoma (HCC).

Main finding: After adjusting for confounding variables, high diastolic WBV was independently associated with extrahepatic metastasis (adjusted odds ratio, 23.41; P < .001) and poor survival (adjusted hazard ratio, 3.81; P < .001) and significantly predicted extrahepatic metastasis at an optimal cutoff of 16 cP (area under the receiver operating characteristic curve, 0.768; P < .001).

Study details: Findings are from a pilot retrospective study including 181 patients with HCC, of which 148 were treatment-naïve having preserved liver function and 33 received nivolumab.

Disclosures: The study was sponsored by Young Medical Scientist Research Grant through the Daewoong Foundation and the Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea. The authors did not declare any conflict of interests.

Source: Han JW et al. PLoS ONE. 2021 Dec 2. doi: 10.1371/journal.pone.0260311.

Key clinical point: High diastolic whole blood viscosity (WBV) may serve as a new independent factor associated with extrahepatic metastasis and poor survival in patients with hepatocellular carcinoma (HCC).

Main finding: After adjusting for confounding variables, high diastolic WBV was independently associated with extrahepatic metastasis (adjusted odds ratio, 23.41; P < .001) and poor survival (adjusted hazard ratio, 3.81; P < .001) and significantly predicted extrahepatic metastasis at an optimal cutoff of 16 cP (area under the receiver operating characteristic curve, 0.768; P < .001).

Study details: Findings are from a pilot retrospective study including 181 patients with HCC, of which 148 were treatment-naïve having preserved liver function and 33 received nivolumab.

Disclosures: The study was sponsored by Young Medical Scientist Research Grant through the Daewoong Foundation and the Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea. The authors did not declare any conflict of interests.

Source: Han JW et al. PLoS ONE. 2021 Dec 2. doi: 10.1371/journal.pone.0260311.

Key clinical point: The modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined radiologic response rate of transarterial chemoembolization (TACE) plus radiotherapy (RT) among patients with advanced hepatocellular carcinoma (HCC) showing macroscopic vascular invasion (MVI) is an independent prognosticator for overall survival (OS).

Main finding: Responders vs nonresponders had significantly longer median OS at 2 months (23.1 months vs 8.0 months; adjusted hazard ratio [aHR], 3.194; P < .001) and 4 months (responders vs nonresponders: 26.5 months vs 9.3 months; aHR, 4.534; P < .001).

Study details: This was a retrospective review study including 427 patients with advanced HCC and MVI who received first-line treatment with TACE plus respiratory-gated 3-dimensional conformal RT in the 2-month analysis, whereas the patient number reduced to 355 in the 4-month analysis.

Disclosures: The study was supported by the Asan Institute for Life Sciences of Asan Medical Center, Seoul, Republic of Korea. The authors declared no conflict of interests.

Source: Jung J et al. Liver Cancer. 2021 Dec 7. doi: 10.1159/000521227.

Key clinical point: The modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined radiologic response rate of transarterial chemoembolization (TACE) plus radiotherapy (RT) among patients with advanced hepatocellular carcinoma (HCC) showing macroscopic vascular invasion (MVI) is an independent prognosticator for overall survival (OS).

Main finding: Responders vs nonresponders had significantly longer median OS at 2 months (23.1 months vs 8.0 months; adjusted hazard ratio [aHR], 3.194; P < .001) and 4 months (responders vs nonresponders: 26.5 months vs 9.3 months; aHR, 4.534; P < .001).

Study details: This was a retrospective review study including 427 patients with advanced HCC and MVI who received first-line treatment with TACE plus respiratory-gated 3-dimensional conformal RT in the 2-month analysis, whereas the patient number reduced to 355 in the 4-month analysis.

Disclosures: The study was supported by the Asan Institute for Life Sciences of Asan Medical Center, Seoul, Republic of Korea. The authors declared no conflict of interests.

Source: Jung J et al. Liver Cancer. 2021 Dec 7. doi: 10.1159/000521227.

Key clinical point: The modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined radiologic response rate of transarterial chemoembolization (TACE) plus radiotherapy (RT) among patients with advanced hepatocellular carcinoma (HCC) showing macroscopic vascular invasion (MVI) is an independent prognosticator for overall survival (OS).

Main finding: Responders vs nonresponders had significantly longer median OS at 2 months (23.1 months vs 8.0 months; adjusted hazard ratio [aHR], 3.194; P < .001) and 4 months (responders vs nonresponders: 26.5 months vs 9.3 months; aHR, 4.534; P < .001).

Study details: This was a retrospective review study including 427 patients with advanced HCC and MVI who received first-line treatment with TACE plus respiratory-gated 3-dimensional conformal RT in the 2-month analysis, whereas the patient number reduced to 355 in the 4-month analysis.

Disclosures: The study was supported by the Asan Institute for Life Sciences of Asan Medical Center, Seoul, Republic of Korea. The authors declared no conflict of interests.

Source: Jung J et al. Liver Cancer. 2021 Dec 7. doi: 10.1159/000521227.

Key clinical point: Hepatic arterial infusion chemotherapy of infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) is better than sorafenib at improving survival in patients with locally advanced hepatocellular carcinoma (HCC).

Main finding: At a median follow-up of 17.1 and 19.8 months, HAIC-FO- and sorafenib-treated patients showed a median overall survival (OS) of 13.9 months (95% CI, 10.6-17.2) and 8.2 months (95% CI, 7.5-9.0), respectively (hazard ratio [HR], 0.408; P = .001), with OS improvements favoring HAIC-FO vs sorafenib in even high-risk patients (10.8 months vs 5.7 months; HR, 0.343; P < .001). Grade 3/4 adverse events were more frequent with sorafenib vs HAIC-FO (48.1% vs20.3%).

Study details: The data come from the open-label, phase 3 FOHAIC-1 trial, which included 262 systemic therapy-naive patients with locally advanced or unresectable HCC who were randomly assigned to receive either HAIC-FO (n=130) or sorafenib (n=132).

Disclosures: The National Natural Science Foundation of China sponsored the study. The authors did not report any potential conflict of interests.

Source: Lyu N et al. J Clin Oncol. 2021 Dec 14. doi: 10.1200/JCO.21.01963.

Key clinical point: Hepatic arterial infusion chemotherapy of infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) is better than sorafenib at improving survival in patients with locally advanced hepatocellular carcinoma (HCC).

Main finding: At a median follow-up of 17.1 and 19.8 months, HAIC-FO- and sorafenib-treated patients showed a median overall survival (OS) of 13.9 months (95% CI, 10.6-17.2) and 8.2 months (95% CI, 7.5-9.0), respectively (hazard ratio [HR], 0.408; P = .001), with OS improvements favoring HAIC-FO vs sorafenib in even high-risk patients (10.8 months vs 5.7 months; HR, 0.343; P < .001). Grade 3/4 adverse events were more frequent with sorafenib vs HAIC-FO (48.1% vs20.3%).

Study details: The data come from the open-label, phase 3 FOHAIC-1 trial, which included 262 systemic therapy-naive patients with locally advanced or unresectable HCC who were randomly assigned to receive either HAIC-FO (n=130) or sorafenib (n=132).

Disclosures: The National Natural Science Foundation of China sponsored the study. The authors did not report any potential conflict of interests.

Source: Lyu N et al. J Clin Oncol. 2021 Dec 14. doi: 10.1200/JCO.21.01963.

Key clinical point: Hepatic arterial infusion chemotherapy of infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) is better than sorafenib at improving survival in patients with locally advanced hepatocellular carcinoma (HCC).

Main finding: At a median follow-up of 17.1 and 19.8 months, HAIC-FO- and sorafenib-treated patients showed a median overall survival (OS) of 13.9 months (95% CI, 10.6-17.2) and 8.2 months (95% CI, 7.5-9.0), respectively (hazard ratio [HR], 0.408; P = .001), with OS improvements favoring HAIC-FO vs sorafenib in even high-risk patients (10.8 months vs 5.7 months; HR, 0.343; P < .001). Grade 3/4 adverse events were more frequent with sorafenib vs HAIC-FO (48.1% vs20.3%).

Study details: The data come from the open-label, phase 3 FOHAIC-1 trial, which included 262 systemic therapy-naive patients with locally advanced or unresectable HCC who were randomly assigned to receive either HAIC-FO (n=130) or sorafenib (n=132).

Disclosures: The National Natural Science Foundation of China sponsored the study. The authors did not report any potential conflict of interests.

Source: Lyu N et al. J Clin Oncol. 2021 Dec 14. doi: 10.1200/JCO.21.01963.

Key clinical point: Longer follow-up results confirm the survival benefits and consistent safety of first-line atezolizumab + bevacizumab vs sorafenib in patients with locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC).

Major finding: After a 15.6-month median follow-up, the median overall survival (19.2 months vs 13.4 months; stratified hazard ratio [HR] for death, 0.66; P < .001) and progression-free survival (6.9 months vs 4.3 months; HR for death/progression, 0.65; P < .001) were higher with atezolizumab + bevacizumab vs sorafenib. Treatment-related grade 3/4 adverse events occurred in 43% vs 46% of patients receiving atezolizumab + bevacizumab vs sorafenib.

Study details: Findings are from a post hoc analysis of the phase 3 IMbrave150 trial including 501 treatment-naïve patients with locally advanced or metastatic and/or unresectable HCC. Patients were randomly assigned to atezolizumab + bevacizumab or sorafenib.

Disclosures: This study was funded by F. Hoffman-La Roche (FHLR)/Genentech. All investigators reported receiving financial or nonfinancial support, providing expert testimony, being an employee of, or holding shares/stocks in various pharmaceutical companies including FHLR/Genentech.

Source: Cheng AL et al. J Hepatol. 2021 Dec 10. doi: 10.1016/j.jhep.2021.11.030.

Key clinical point: Longer follow-up results confirm the survival benefits and consistent safety of first-line atezolizumab + bevacizumab vs sorafenib in patients with locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC).

Major finding: After a 15.6-month median follow-up, the median overall survival (19.2 months vs 13.4 months; stratified hazard ratio [HR] for death, 0.66; P < .001) and progression-free survival (6.9 months vs 4.3 months; HR for death/progression, 0.65; P < .001) were higher with atezolizumab + bevacizumab vs sorafenib. Treatment-related grade 3/4 adverse events occurred in 43% vs 46% of patients receiving atezolizumab + bevacizumab vs sorafenib.

Study details: Findings are from a post hoc analysis of the phase 3 IMbrave150 trial including 501 treatment-naïve patients with locally advanced or metastatic and/or unresectable HCC. Patients were randomly assigned to atezolizumab + bevacizumab or sorafenib.

Disclosures: This study was funded by F. Hoffman-La Roche (FHLR)/Genentech. All investigators reported receiving financial or nonfinancial support, providing expert testimony, being an employee of, or holding shares/stocks in various pharmaceutical companies including FHLR/Genentech.

Source: Cheng AL et al. J Hepatol. 2021 Dec 10. doi: 10.1016/j.jhep.2021.11.030.

Key clinical point: Longer follow-up results confirm the survival benefits and consistent safety of first-line atezolizumab + bevacizumab vs sorafenib in patients with locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC).

Major finding: After a 15.6-month median follow-up, the median overall survival (19.2 months vs 13.4 months; stratified hazard ratio [HR] for death, 0.66; P < .001) and progression-free survival (6.9 months vs 4.3 months; HR for death/progression, 0.65; P < .001) were higher with atezolizumab + bevacizumab vs sorafenib. Treatment-related grade 3/4 adverse events occurred in 43% vs 46% of patients receiving atezolizumab + bevacizumab vs sorafenib.

Study details: Findings are from a post hoc analysis of the phase 3 IMbrave150 trial including 501 treatment-naïve patients with locally advanced or metastatic and/or unresectable HCC. Patients were randomly assigned to atezolizumab + bevacizumab or sorafenib.

Disclosures: This study was funded by F. Hoffman-La Roche (FHLR)/Genentech. All investigators reported receiving financial or nonfinancial support, providing expert testimony, being an employee of, or holding shares/stocks in various pharmaceutical companies including FHLR/Genentech.

Source: Cheng AL et al. J Hepatol. 2021 Dec 10. doi: 10.1016/j.jhep.2021.11.030.

Key clinical point: First-line nivolumab treatment did not improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib.

Major finding: At a minimum follow-up of 22.8 months, nivolumab vs sorafenib did not meet the prespecified significance boundary for superior overall survival (16.4 months vs 14.7 months; hazard ratio, 0.85; P = .075).

Study details: Findings are from the phase 3 CheckMate 459 trial including 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372).

Disclosures: This study was supported by Bristol Myers Squibb (BMS) and Ono Pharmaceutical. Some investigators including the lead author reported receiving grants and fees from, participation on data safety monitoring board or advisory boards for, owning stocks in, and being an employee of various pharmaceutical companies, including BMS and Ono Pharmaceutical.

Source: Yau T et al. Lancet Oncol. 2021 Dec 13. doi: 10.1016/S1470-2045(21)00604-5.

Key clinical point: First-line nivolumab treatment did not improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib.

Major finding: At a minimum follow-up of 22.8 months, nivolumab vs sorafenib did not meet the prespecified significance boundary for superior overall survival (16.4 months vs 14.7 months; hazard ratio, 0.85; P = .075).

Study details: Findings are from the phase 3 CheckMate 459 trial including 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372).

Disclosures: This study was supported by Bristol Myers Squibb (BMS) and Ono Pharmaceutical. Some investigators including the lead author reported receiving grants and fees from, participation on data safety monitoring board or advisory boards for, owning stocks in, and being an employee of various pharmaceutical companies, including BMS and Ono Pharmaceutical.

Source: Yau T et al. Lancet Oncol. 2021 Dec 13. doi: 10.1016/S1470-2045(21)00604-5.

Key clinical point: First-line nivolumab treatment did not improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib.

Major finding: At a minimum follow-up of 22.8 months, nivolumab vs sorafenib did not meet the prespecified significance boundary for superior overall survival (16.4 months vs 14.7 months; hazard ratio, 0.85; P = .075).

Study details: Findings are from the phase 3 CheckMate 459 trial including 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372).

Disclosures: This study was supported by Bristol Myers Squibb (BMS) and Ono Pharmaceutical. Some investigators including the lead author reported receiving grants and fees from, participation on data safety monitoring board or advisory boards for, owning stocks in, and being an employee of various pharmaceutical companies, including BMS and Ono Pharmaceutical.

Source: Yau T et al. Lancet Oncol. 2021 Dec 13. doi: 10.1016/S1470-2045(21)00604-5.

A steroid-free clinical response had no impact on multiple components of Crohn’s disease progression, based on data from 95 adults.

The therapeutic goals of Crohn’s disease have evolved from controlling symptoms to blocking disease progression and reducing complications, wrote David Laharie, MD, of Hôpital Haut-Lévêque, Pessac, France, and colleagues. The goal of steroid-free remission has been used as an endpoint of treatment, but data on the impact of such remission on long-term disease are limited, the researchers noted in a retrospective study published in Clinical Gastroenterology and Hepatology.

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In the study, the researchers reviewed data from 95 adults with early Crohn’s disease (CD) who participated in the TAILORIX trial involving treatment with infliximab and immunosuppressants. The primary endpoint of the TAILORIX trial was sustained corticosteroid-free remission from week 22 to 54. In the current study, the primary endpoint was progression-free survival at 1, 3, and 5 years in patients who did or did not meet the TAILORIX primary endpoint. The median disease duration was 4.5 months, and the median follow-up was 64.2 months.

Progression-free survival was defined as a composite of luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment during the follow-up period.

In the study population, 45 patients achieved corticosteroid-free remission and 50 did not. At 54 weeks, 17 patients with corticosteroid-free remission (38%) and 28 patients without remission (56%) achieved complete mucosal healing, and progression-free survival rates were similar between these groups.

Overall, the rates of progression-free survival at 1, 3, and 5 years were not significantly different between the remission and nonremission groups: 86% versus 91%, respectively, at 1 year; 70% for both groups at 3 years; and 64% and 61%, respectively, at 5 years.

The researchers also compared individual components of the primary endpoint (luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment), and found no significant differences in survival rates in patients who had and had not achieved steroid-free remission.

Survival rates without luminal surgery at 1, 3, and 5 years were 97% versus 96%, 93% versus 90%, and 87% versus 82%, respectively, for remission and nonremission groups. Similarly, survival rates without anal surgery were 93%, 86%, and 86% versus 96%, 88%, and 85%, respectively, for the two groups. Rates of hospitalization-free survival at 1, 3, and 5 years were 90% versus 92%, 81% versus 81%, and 78% versus 69%, respectively, in the remission and nonremission groups. Survival rates without a new systemic CD treatment also were similar at 1, 3, and 5 years: 93% versus 95%, 71% versus 93%, and 60% versus 51%, respectively, for the remission and nonremission groups.

CD progression was not associated with not achieving corticosteroid-free remission (hazard ratio, 0.861). Other factors that were not associated with disease progression in this study included CRP greater than 5 mg/L, age older than 30 years, active smoking, and B1 phenotype.

The researchers noted that, although endoscopic and clinical remission is currently recommended for CD, “there is no validated or standardized definition of this endoscopic goal.” The high rates of survival without major abdominal surgery, regardless of remission status, suggest a significant impact of early combination therapy for CD patients who were biologic naive. Other studies have shown similar improved outcomes for CD patients with early treatment.

The study findings were limited by several factors including the retrospective design and lack of power to compare long-term progression-free survival, the researchers noted. However, the results were strengthened by the robust data on hospitalizations and surgeries from the TAILORIX trial.

The results support a more flexible strategy for CD, “recommending endoscopic and clinical remission in early diagnosed patients and less stringent objectives in those with more refractory or advanced disease,” they concluded.
 

Findings may guide patient management

The current study is important to help clinicians know whether CD patients who achieve a short-term, steroid-free clinical and endoscopic remission go on to experience better long-term disease outcomes than those who do not achieve this short-term remission, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

Dr. Sakuraba said that he was surprised by the study findings. “Achieving a clinical remission off steroids with complete endoscopic remission, i.e., deep remission, is considered a treatment goal, but the fact that it did not result in less disease progression was surprising.”

The take-home message for clinicians from the study is that CD patients may still experience disease progression after achieving a single time of clinical and endoscopic remission “mainly due to loss of response to infliximab, so continued long-term disease monitoring and control are required,” Dr. Sakuraba said.

The current study was a post hoc follow-up analysis of a previous trial, Dr. Sakuraba noted. Therefore, studies primarily focused on changing the disease progression and natural course of CD are warranted.

Dr. Laharie disclosed counseling, boards, transportation, or fees from AbbVie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, and Tillots. Dr. Sakuraba had no relevant financial conflicts to disclose.

A steroid-free clinical response had no impact on multiple components of Crohn’s disease progression, based on data from 95 adults.

The therapeutic goals of Crohn’s disease have evolved from controlling symptoms to blocking disease progression and reducing complications, wrote David Laharie, MD, of Hôpital Haut-Lévêque, Pessac, France, and colleagues. The goal of steroid-free remission has been used as an endpoint of treatment, but data on the impact of such remission on long-term disease are limited, the researchers noted in a retrospective study published in Clinical Gastroenterology and Hepatology.

undefined undefined/iStock/Getty Images

In the study, the researchers reviewed data from 95 adults with early Crohn’s disease (CD) who participated in the TAILORIX trial involving treatment with infliximab and immunosuppressants. The primary endpoint of the TAILORIX trial was sustained corticosteroid-free remission from week 22 to 54. In the current study, the primary endpoint was progression-free survival at 1, 3, and 5 years in patients who did or did not meet the TAILORIX primary endpoint. The median disease duration was 4.5 months, and the median follow-up was 64.2 months.

Progression-free survival was defined as a composite of luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment during the follow-up period.

In the study population, 45 patients achieved corticosteroid-free remission and 50 did not. At 54 weeks, 17 patients with corticosteroid-free remission (38%) and 28 patients without remission (56%) achieved complete mucosal healing, and progression-free survival rates were similar between these groups.

Overall, the rates of progression-free survival at 1, 3, and 5 years were not significantly different between the remission and nonremission groups: 86% versus 91%, respectively, at 1 year; 70% for both groups at 3 years; and 64% and 61%, respectively, at 5 years.

The researchers also compared individual components of the primary endpoint (luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment), and found no significant differences in survival rates in patients who had and had not achieved steroid-free remission.

Survival rates without luminal surgery at 1, 3, and 5 years were 97% versus 96%, 93% versus 90%, and 87% versus 82%, respectively, for remission and nonremission groups. Similarly, survival rates without anal surgery were 93%, 86%, and 86% versus 96%, 88%, and 85%, respectively, for the two groups. Rates of hospitalization-free survival at 1, 3, and 5 years were 90% versus 92%, 81% versus 81%, and 78% versus 69%, respectively, in the remission and nonremission groups. Survival rates without a new systemic CD treatment also were similar at 1, 3, and 5 years: 93% versus 95%, 71% versus 93%, and 60% versus 51%, respectively, for the remission and nonremission groups.

CD progression was not associated with not achieving corticosteroid-free remission (hazard ratio, 0.861). Other factors that were not associated with disease progression in this study included CRP greater than 5 mg/L, age older than 30 years, active smoking, and B1 phenotype.

The researchers noted that, although endoscopic and clinical remission is currently recommended for CD, “there is no validated or standardized definition of this endoscopic goal.” The high rates of survival without major abdominal surgery, regardless of remission status, suggest a significant impact of early combination therapy for CD patients who were biologic naive. Other studies have shown similar improved outcomes for CD patients with early treatment.

The study findings were limited by several factors including the retrospective design and lack of power to compare long-term progression-free survival, the researchers noted. However, the results were strengthened by the robust data on hospitalizations and surgeries from the TAILORIX trial.

The results support a more flexible strategy for CD, “recommending endoscopic and clinical remission in early diagnosed patients and less stringent objectives in those with more refractory or advanced disease,” they concluded.
 

Findings may guide patient management

The current study is important to help clinicians know whether CD patients who achieve a short-term, steroid-free clinical and endoscopic remission go on to experience better long-term disease outcomes than those who do not achieve this short-term remission, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

Dr. Sakuraba said that he was surprised by the study findings. “Achieving a clinical remission off steroids with complete endoscopic remission, i.e., deep remission, is considered a treatment goal, but the fact that it did not result in less disease progression was surprising.”

The take-home message for clinicians from the study is that CD patients may still experience disease progression after achieving a single time of clinical and endoscopic remission “mainly due to loss of response to infliximab, so continued long-term disease monitoring and control are required,” Dr. Sakuraba said.

The current study was a post hoc follow-up analysis of a previous trial, Dr. Sakuraba noted. Therefore, studies primarily focused on changing the disease progression and natural course of CD are warranted.

Dr. Laharie disclosed counseling, boards, transportation, or fees from AbbVie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, and Tillots. Dr. Sakuraba had no relevant financial conflicts to disclose.

A steroid-free clinical response had no impact on multiple components of Crohn’s disease progression, based on data from 95 adults.

The therapeutic goals of Crohn’s disease have evolved from controlling symptoms to blocking disease progression and reducing complications, wrote David Laharie, MD, of Hôpital Haut-Lévêque, Pessac, France, and colleagues. The goal of steroid-free remission has been used as an endpoint of treatment, but data on the impact of such remission on long-term disease are limited, the researchers noted in a retrospective study published in Clinical Gastroenterology and Hepatology.

undefined undefined/iStock/Getty Images

In the study, the researchers reviewed data from 95 adults with early Crohn’s disease (CD) who participated in the TAILORIX trial involving treatment with infliximab and immunosuppressants. The primary endpoint of the TAILORIX trial was sustained corticosteroid-free remission from week 22 to 54. In the current study, the primary endpoint was progression-free survival at 1, 3, and 5 years in patients who did or did not meet the TAILORIX primary endpoint. The median disease duration was 4.5 months, and the median follow-up was 64.2 months.

Progression-free survival was defined as a composite of luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment during the follow-up period.

In the study population, 45 patients achieved corticosteroid-free remission and 50 did not. At 54 weeks, 17 patients with corticosteroid-free remission (38%) and 28 patients without remission (56%) achieved complete mucosal healing, and progression-free survival rates were similar between these groups.

Overall, the rates of progression-free survival at 1, 3, and 5 years were not significantly different between the remission and nonremission groups: 86% versus 91%, respectively, at 1 year; 70% for both groups at 3 years; and 64% and 61%, respectively, at 5 years.

The researchers also compared individual components of the primary endpoint (luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment), and found no significant differences in survival rates in patients who had and had not achieved steroid-free remission.

Survival rates without luminal surgery at 1, 3, and 5 years were 97% versus 96%, 93% versus 90%, and 87% versus 82%, respectively, for remission and nonremission groups. Similarly, survival rates without anal surgery were 93%, 86%, and 86% versus 96%, 88%, and 85%, respectively, for the two groups. Rates of hospitalization-free survival at 1, 3, and 5 years were 90% versus 92%, 81% versus 81%, and 78% versus 69%, respectively, in the remission and nonremission groups. Survival rates without a new systemic CD treatment also were similar at 1, 3, and 5 years: 93% versus 95%, 71% versus 93%, and 60% versus 51%, respectively, for the remission and nonremission groups.

CD progression was not associated with not achieving corticosteroid-free remission (hazard ratio, 0.861). Other factors that were not associated with disease progression in this study included CRP greater than 5 mg/L, age older than 30 years, active smoking, and B1 phenotype.

The researchers noted that, although endoscopic and clinical remission is currently recommended for CD, “there is no validated or standardized definition of this endoscopic goal.” The high rates of survival without major abdominal surgery, regardless of remission status, suggest a significant impact of early combination therapy for CD patients who were biologic naive. Other studies have shown similar improved outcomes for CD patients with early treatment.

The study findings were limited by several factors including the retrospective design and lack of power to compare long-term progression-free survival, the researchers noted. However, the results were strengthened by the robust data on hospitalizations and surgeries from the TAILORIX trial.

The results support a more flexible strategy for CD, “recommending endoscopic and clinical remission in early diagnosed patients and less stringent objectives in those with more refractory or advanced disease,” they concluded.
 

Findings may guide patient management

The current study is important to help clinicians know whether CD patients who achieve a short-term, steroid-free clinical and endoscopic remission go on to experience better long-term disease outcomes than those who do not achieve this short-term remission, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

Dr. Sakuraba said that he was surprised by the study findings. “Achieving a clinical remission off steroids with complete endoscopic remission, i.e., deep remission, is considered a treatment goal, but the fact that it did not result in less disease progression was surprising.”

The take-home message for clinicians from the study is that CD patients may still experience disease progression after achieving a single time of clinical and endoscopic remission “mainly due to loss of response to infliximab, so continued long-term disease monitoring and control are required,” Dr. Sakuraba said.

The current study was a post hoc follow-up analysis of a previous trial, Dr. Sakuraba noted. Therefore, studies primarily focused on changing the disease progression and natural course of CD are warranted.

Dr. Laharie disclosed counseling, boards, transportation, or fees from AbbVie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, and Tillots. Dr. Sakuraba had no relevant financial conflicts to disclose.

In the opinion of Raj Chovatiya, MD, PhD, the longitudinal course of atopic dermatitis (AD) is an important yet overlooked clinical domain of the disease.

“We know that AD is associated with fluctuating severity, disease flares, long-term persistence, and periods of quiescence, but its longitudinal course is not routinely incorporated into guidelines or clinical trials,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis virtual symposium. “Understanding the long-term course may improve our ability to phenotype, prognosticate, and personalize our care.”

The classic view of AD is that it starts in early childhood, follows a waxing and waning course for a few years, and burns out by adulthood. “I think we all know that this is generally false,” he said. “This was largely based on anecdotal clinical experience and large cross-sectional studies, not ones that consider the heterogeneity of AD.”

Results from a large-scale, prospective study of 7,157 children enrolled in the Pediatric Eczema Elective Registry (PEER), suggests that AD commonly persists beyond adulthood. PEER was a phase IV postmarketing safety study of children aged 12-17 with moderate to severe AD who were exposed to topical pimecrolimus and who were surveyed every 6 months (JAMA Dermatol. 2014;150[6]:593-600). The researchers found that more persistent disease was associated with self-reported disease activity, many environmental exposures, White race, history of AD, and an annual household income of less than $50,000. By age 20, 50% reported at least one 6-month symptom- and medication-free period. “The important takeaway was that at every age, greater than 80% reported active AD as defined by symptoms or medication use, meaning that persistence was extremely high – much higher than what was originally thought,” Dr. Chovatiya said. “If you take a look at the literature before this study, many were retrospective analyses, and persistence was estimated to be in the 40%-60% range.”

International prospective studies have provided a more conservative estimate of persistence. For example, the German Multicenter Allergy Study followed 1,314 from birth through age 7 (J Allergy Clin Immunol. 2004;113[5]:925-31). Of these, 22% had AD within the first 2 years of life. Of these, 43% were in remission by age 3, while 38% had intermittent AD, and 19% had symptoms every year of the study. “Studies of other birth cohorts in the world came out suggesting that the rates of AD persistence ranges in the single digits to the teens,” Dr. Chovatiya said.

To reconcile these heterogeneous estimates of AD persistence, researchers conducted a systematic review and meta-analysis of 45 studies that included 110,651 subjects from 15 countries and spanned 434,992 patient-years (J Am Acad Dermatol. 2016;75:681-7.e11). They found that 80% of childhood AD had at least one observed period of disease clearance by 8 years of age. “Most importantly, less than 5% of childhood AD was persistent 20 years after diagnosis,” Dr. Chovatiya said. “However, interestingly, increased persistence was associated with later onset AD, more years of persistence, and more patient/caregiver-assessed disease.” He pointed out inherent limitations to all studies of AD persistence, including nonuniform methods of data collection, differing cohorts, different ways of diagnosing AD, different disease severity scales, and the fact that most don’t assess flares or recurrence beyond the initial period of disease clearance. “This can lead to a potential underestimation of longer-term persistence,” he said.

Childhood AD features unique predictors of persistence that may define AD trajectories. For example, in several existing studies, more persistent disease was associated with higher baseline severity, earlier-onset AD, personal history of atopy, family history of AD, AD genetic risk score (heritability, including common Filaggrin mutations), urban environment, non-White race, Hispanic ethnicity, female sex, lower household income, and overall poorer health status.

“When it comes to evaluating the longitudinal course of AD in clinical practice, consideration of fluctuation, persistence, and improvement over time may actually improve our clinical decision-making and help set realistic expectations for our patients,” Dr. Chovatiya said. “I think that AD classification can take a lesson from asthma. When we think about how our allergy colleagues think about asthma, it is commonly classified as intermittent, mild persistent, moderate persistent, and severe persistent. Those that have intermittent disease get reactive treatment, while those with persistent disease get proactive treatment. Similarly, AD could be classified as mild intermittent, mild persistent, moderate to severe intermittent and moderate to severe persistent.”

He concluded his presentation by recommending that the fluctuating course of AD be better captured in clinical trials. “Current randomized, controlled trials use validated measures of AD signs and symptoms as inclusion criteria and measures of efficacy,” he said. “Static assessments may confound treatment effects, and assessment of prespecified time points are somewhat arbitrary in the context of disease subsets.” He proposes studies that examine aggregate measures of long-term disease control, such as number of itch-free days, weeks with clear skin, and flares experienced. “Long-term control assessment in RCTs should include signs, symptoms, health-related quality of life, and a patient global domain over time to better understand how AD is doing in the long run,” he said.

Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arcutis, Arena, Incyte, Pfizer, Regeneron, and Sanofi Genzyme.

[email protected]

In the opinion of Raj Chovatiya, MD, PhD, the longitudinal course of atopic dermatitis (AD) is an important yet overlooked clinical domain of the disease.

“We know that AD is associated with fluctuating severity, disease flares, long-term persistence, and periods of quiescence, but its longitudinal course is not routinely incorporated into guidelines or clinical trials,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis virtual symposium. “Understanding the long-term course may improve our ability to phenotype, prognosticate, and personalize our care.”

The classic view of AD is that it starts in early childhood, follows a waxing and waning course for a few years, and burns out by adulthood. “I think we all know that this is generally false,” he said. “This was largely based on anecdotal clinical experience and large cross-sectional studies, not ones that consider the heterogeneity of AD.”

Results from a large-scale, prospective study of 7,157 children enrolled in the Pediatric Eczema Elective Registry (PEER), suggests that AD commonly persists beyond adulthood. PEER was a phase IV postmarketing safety study of children aged 12-17 with moderate to severe AD who were exposed to topical pimecrolimus and who were surveyed every 6 months (JAMA Dermatol. 2014;150[6]:593-600). The researchers found that more persistent disease was associated with self-reported disease activity, many environmental exposures, White race, history of AD, and an annual household income of less than $50,000. By age 20, 50% reported at least one 6-month symptom- and medication-free period. “The important takeaway was that at every age, greater than 80% reported active AD as defined by symptoms or medication use, meaning that persistence was extremely high – much higher than what was originally thought,” Dr. Chovatiya said. “If you take a look at the literature before this study, many were retrospective analyses, and persistence was estimated to be in the 40%-60% range.”

International prospective studies have provided a more conservative estimate of persistence. For example, the German Multicenter Allergy Study followed 1,314 from birth through age 7 (J Allergy Clin Immunol. 2004;113[5]:925-31). Of these, 22% had AD within the first 2 years of life. Of these, 43% were in remission by age 3, while 38% had intermittent AD, and 19% had symptoms every year of the study. “Studies of other birth cohorts in the world came out suggesting that the rates of AD persistence ranges in the single digits to the teens,” Dr. Chovatiya said.

To reconcile these heterogeneous estimates of AD persistence, researchers conducted a systematic review and meta-analysis of 45 studies that included 110,651 subjects from 15 countries and spanned 434,992 patient-years (J Am Acad Dermatol. 2016;75:681-7.e11). They found that 80% of childhood AD had at least one observed period of disease clearance by 8 years of age. “Most importantly, less than 5% of childhood AD was persistent 20 years after diagnosis,” Dr. Chovatiya said. “However, interestingly, increased persistence was associated with later onset AD, more years of persistence, and more patient/caregiver-assessed disease.” He pointed out inherent limitations to all studies of AD persistence, including nonuniform methods of data collection, differing cohorts, different ways of diagnosing AD, different disease severity scales, and the fact that most don’t assess flares or recurrence beyond the initial period of disease clearance. “This can lead to a potential underestimation of longer-term persistence,” he said.

Childhood AD features unique predictors of persistence that may define AD trajectories. For example, in several existing studies, more persistent disease was associated with higher baseline severity, earlier-onset AD, personal history of atopy, family history of AD, AD genetic risk score (heritability, including common Filaggrin mutations), urban environment, non-White race, Hispanic ethnicity, female sex, lower household income, and overall poorer health status.

“When it comes to evaluating the longitudinal course of AD in clinical practice, consideration of fluctuation, persistence, and improvement over time may actually improve our clinical decision-making and help set realistic expectations for our patients,” Dr. Chovatiya said. “I think that AD classification can take a lesson from asthma. When we think about how our allergy colleagues think about asthma, it is commonly classified as intermittent, mild persistent, moderate persistent, and severe persistent. Those that have intermittent disease get reactive treatment, while those with persistent disease get proactive treatment. Similarly, AD could be classified as mild intermittent, mild persistent, moderate to severe intermittent and moderate to severe persistent.”

He concluded his presentation by recommending that the fluctuating course of AD be better captured in clinical trials. “Current randomized, controlled trials use validated measures of AD signs and symptoms as inclusion criteria and measures of efficacy,” he said. “Static assessments may confound treatment effects, and assessment of prespecified time points are somewhat arbitrary in the context of disease subsets.” He proposes studies that examine aggregate measures of long-term disease control, such as number of itch-free days, weeks with clear skin, and flares experienced. “Long-term control assessment in RCTs should include signs, symptoms, health-related quality of life, and a patient global domain over time to better understand how AD is doing in the long run,” he said.

Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arcutis, Arena, Incyte, Pfizer, Regeneron, and Sanofi Genzyme.

[email protected]

In the opinion of Raj Chovatiya, MD, PhD, the longitudinal course of atopic dermatitis (AD) is an important yet overlooked clinical domain of the disease.

“We know that AD is associated with fluctuating severity, disease flares, long-term persistence, and periods of quiescence, but its longitudinal course is not routinely incorporated into guidelines or clinical trials,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis virtual symposium. “Understanding the long-term course may improve our ability to phenotype, prognosticate, and personalize our care.”

The classic view of AD is that it starts in early childhood, follows a waxing and waning course for a few years, and burns out by adulthood. “I think we all know that this is generally false,” he said. “This was largely based on anecdotal clinical experience and large cross-sectional studies, not ones that consider the heterogeneity of AD.”

Results from a large-scale, prospective study of 7,157 children enrolled in the Pediatric Eczema Elective Registry (PEER), suggests that AD commonly persists beyond adulthood. PEER was a phase IV postmarketing safety study of children aged 12-17 with moderate to severe AD who were exposed to topical pimecrolimus and who were surveyed every 6 months (JAMA Dermatol. 2014;150[6]:593-600). The researchers found that more persistent disease was associated with self-reported disease activity, many environmental exposures, White race, history of AD, and an annual household income of less than $50,000. By age 20, 50% reported at least one 6-month symptom- and medication-free period. “The important takeaway was that at every age, greater than 80% reported active AD as defined by symptoms or medication use, meaning that persistence was extremely high – much higher than what was originally thought,” Dr. Chovatiya said. “If you take a look at the literature before this study, many were retrospective analyses, and persistence was estimated to be in the 40%-60% range.”

International prospective studies have provided a more conservative estimate of persistence. For example, the German Multicenter Allergy Study followed 1,314 from birth through age 7 (J Allergy Clin Immunol. 2004;113[5]:925-31). Of these, 22% had AD within the first 2 years of life. Of these, 43% were in remission by age 3, while 38% had intermittent AD, and 19% had symptoms every year of the study. “Studies of other birth cohorts in the world came out suggesting that the rates of AD persistence ranges in the single digits to the teens,” Dr. Chovatiya said.

To reconcile these heterogeneous estimates of AD persistence, researchers conducted a systematic review and meta-analysis of 45 studies that included 110,651 subjects from 15 countries and spanned 434,992 patient-years (J Am Acad Dermatol. 2016;75:681-7.e11). They found that 80% of childhood AD had at least one observed period of disease clearance by 8 years of age. “Most importantly, less than 5% of childhood AD was persistent 20 years after diagnosis,” Dr. Chovatiya said. “However, interestingly, increased persistence was associated with later onset AD, more years of persistence, and more patient/caregiver-assessed disease.” He pointed out inherent limitations to all studies of AD persistence, including nonuniform methods of data collection, differing cohorts, different ways of diagnosing AD, different disease severity scales, and the fact that most don’t assess flares or recurrence beyond the initial period of disease clearance. “This can lead to a potential underestimation of longer-term persistence,” he said.

Childhood AD features unique predictors of persistence that may define AD trajectories. For example, in several existing studies, more persistent disease was associated with higher baseline severity, earlier-onset AD, personal history of atopy, family history of AD, AD genetic risk score (heritability, including common Filaggrin mutations), urban environment, non-White race, Hispanic ethnicity, female sex, lower household income, and overall poorer health status.

“When it comes to evaluating the longitudinal course of AD in clinical practice, consideration of fluctuation, persistence, and improvement over time may actually improve our clinical decision-making and help set realistic expectations for our patients,” Dr. Chovatiya said. “I think that AD classification can take a lesson from asthma. When we think about how our allergy colleagues think about asthma, it is commonly classified as intermittent, mild persistent, moderate persistent, and severe persistent. Those that have intermittent disease get reactive treatment, while those with persistent disease get proactive treatment. Similarly, AD could be classified as mild intermittent, mild persistent, moderate to severe intermittent and moderate to severe persistent.”

He concluded his presentation by recommending that the fluctuating course of AD be better captured in clinical trials. “Current randomized, controlled trials use validated measures of AD signs and symptoms as inclusion criteria and measures of efficacy,” he said. “Static assessments may confound treatment effects, and assessment of prespecified time points are somewhat arbitrary in the context of disease subsets.” He proposes studies that examine aggregate measures of long-term disease control, such as number of itch-free days, weeks with clear skin, and flares experienced. “Long-term control assessment in RCTs should include signs, symptoms, health-related quality of life, and a patient global domain over time to better understand how AD is doing in the long run,” he said.

Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arcutis, Arena, Incyte, Pfizer, Regeneron, and Sanofi Genzyme.

[email protected]

In more than 15% of people with benign adrenal tumors, the growths produce clinically relevant levels of serum cortisol that are significantly linked with an increased prevalence of hypertension and, in 5% of those with Cushing syndrome (CS), an increased prevalence of type 2 diabetes, based on data from more than 1,300 people with benign adrenal tumors, the largest reported prospective study of the disorder.

The study results showed that mild autonomous cortisol secretion (MACS) from benign adrenal tumors “is very frequent and is an important risk condition for high blood pressure and type 2 diabetes, especially in older women,” said Alessandro Prete, MD, lead author of the study which was published online Jan. 3, 2022, in Annals of Internal Medicine.

SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY/Getty Images

“The impact of MACS on high blood pressure and risk for type 2 diabetes has been underestimated until now,” said Dr. Prete, an endocrinologist at the University of Birmingham (England), in a written statement. 

Results from previous studies “suggested that MACS is associated with poor health. Our study is the largest to establish conclusively the extent of the risk and severity of high blood pressure and type 2 diabetes in patients with MACS,” said Wiebke Arlt, MD, DSc, senior author and director of the Institute of Metabolism & Systems Research at the University of Birmingham.

All patients found to have a benign adrenal tumor should undergo testing for MACS and have their blood pressure and glucose levels measured regularly, Dr. Arlt advised in the statement released by the University of Birmingham.
 

MACS more common than previously thought

The new findings show that MACS “is more common and may have a more negative impact on health than previously thought, including increasing the risk for type 2 diabetes,” commented Lucy Chambers, PhD, head of research communications at Diabetes UK. “The findings suggest that screening for MACS could help identify people – particularly women, in whom the condition was found to be more common – who may benefit from support to reduce their risk of type 2 diabetes.”

The study included 1,305 people with newly diagnosed, benign adrenal tumors greater than 1 cm, a subset of patients prospectively enrolled in a study with the primary purpose of validating a novel way to diagnose adrenocortical carcinomas. Patients underwent treatment in 2011-2016 at any of 14 tertiary centers in 11 countries.

Researchers used a MACS definition of failure to suppress morning serum cortisol concentration to less than 50 nmol/L after treatment with 1 mg oral dexamethasone at 11 p.m. the previous evening in those with no clinical features of CS.

Roughly half of patients (n = 649) showed normal cortisol suppression with dexamethasone, identifying them as having nonfunctioning adrenal tumors, and about 35% showed possible MACS based on having moderate levels of excess cortisol.

Nearly 11% (n = 140) showed definitive MACS with more robust cortisol levels, and 5% (n = 65) received a diagnosis of clinically overt CS despite selection criteria meant to exclude people with clinical signs of CS.

There was a clear relationship between patient sex and severity of autonomous cortisol production. Among those with nonfunctioning adrenal tumors, 64% were women, which rose to 74% women in those with definitive MACS and 86% women among those with CS. The median age of participants was 60 years old.
 

Increasing cortisol levels linked with cardiometabolic disease

Analysis of the prevalence of hypertension and type 2 diabetes after adjustment for age, sex, and body mass index showed that, compared with people with nonfunctioning adrenal tumors, those with definitive MACS had a significant 15% higher rate of hypertension and those with overt CS had a 37% higher rate. 

Higher levels of excess cortisol were also directly linked with an increased need for treatment with three or more antihypertensive agents to control blood pressure. Those with definitive MACS had a significant 31% higher rate of being on three or more drugs, and those with overt CS had a greater than twofold higher rate.

People with overt CS also had a significant 62% higher rate of type 2 diabetes, compared with those with a nonfunctioning tumor, but in those with definitive MACS the association was not significant. However, people with definitive MACS or overt CS who had type 2 diabetes and also had significantly increased rates of requiring insulin treatment.

The findings show that “people with definitive MACS carry an increased cardiometabolic burden similar to that seen in CS even if they do not display typical features of clinically overt cortisol excess,” the authors wrote in the report.

Even among those with apparently nonfunctioning tumors, each 10 nmol/L rise in cortisol level during a dexamethasone-suppression test was associated with a higher cardiometabolic disease burden. This observation suggests that current diagnostic cutoffs for the suppression test may miss some people with clinically relevant autonomous cortisol secretion, the report said. The study findings also suggest that people with benign adrenal tumors show a progressive continuum of excess cortisol with clinical consequences that increase as levels increase.
 

Determine the consequences of cortisol secretion

“These data clearly support the European Society of Endocrinology guideline recommendations that clinicians should determine precisely the cardiometabolic consequences of mild cortisol secretion in patients with adrenal lesions,” André Lacroix, MD, wrote in an accompanying editorial.

But Dr. Lacroix included some caveats. He noted the “potential pitfalls in relying on a single total serum cortisol value after the 1-mg dexamethasone test.” He also wondered whether the analysis used optimal cortisol values to distinguish patient subgroups.

Plus, “even in patients with nonfunctioning adrenal tumors the prevalence of diabetes and hypertension is higher than in the general population, raising concerns about the cardiometabolic consequences of barely detectable cortisol excess,” wrote Dr. Lacroix, an endocrinologist at the CHUM Research Center and professor of medicine at the University of Montreal.

The study received no commercial funding. Dr. Prete, Dr. Chambers, and Dr. Lacroix have reported no relevant financial relationships. Dr. Arlt is listed as an inventor on a patent on the use of steroid profiling as a biomarker tool for the differential diagnosis of adrenal tumors.

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

In more than 15% of people with benign adrenal tumors, the growths produce clinically relevant levels of serum cortisol that are significantly linked with an increased prevalence of hypertension and, in 5% of those with Cushing syndrome (CS), an increased prevalence of type 2 diabetes, based on data from more than 1,300 people with benign adrenal tumors, the largest reported prospective study of the disorder.

The study results showed that mild autonomous cortisol secretion (MACS) from benign adrenal tumors “is very frequent and is an important risk condition for high blood pressure and type 2 diabetes, especially in older women,” said Alessandro Prete, MD, lead author of the study which was published online Jan. 3, 2022, in Annals of Internal Medicine.

SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY/Getty Images

“The impact of MACS on high blood pressure and risk for type 2 diabetes has been underestimated until now,” said Dr. Prete, an endocrinologist at the University of Birmingham (England), in a written statement. 

Results from previous studies “suggested that MACS is associated with poor health. Our study is the largest to establish conclusively the extent of the risk and severity of high blood pressure and type 2 diabetes in patients with MACS,” said Wiebke Arlt, MD, DSc, senior author and director of the Institute of Metabolism & Systems Research at the University of Birmingham.

All patients found to have a benign adrenal tumor should undergo testing for MACS and have their blood pressure and glucose levels measured regularly, Dr. Arlt advised in the statement released by the University of Birmingham.
 

MACS more common than previously thought

The new findings show that MACS “is more common and may have a more negative impact on health than previously thought, including increasing the risk for type 2 diabetes,” commented Lucy Chambers, PhD, head of research communications at Diabetes UK. “The findings suggest that screening for MACS could help identify people – particularly women, in whom the condition was found to be more common – who may benefit from support to reduce their risk of type 2 diabetes.”

The study included 1,305 people with newly diagnosed, benign adrenal tumors greater than 1 cm, a subset of patients prospectively enrolled in a study with the primary purpose of validating a novel way to diagnose adrenocortical carcinomas. Patients underwent treatment in 2011-2016 at any of 14 tertiary centers in 11 countries.

Researchers used a MACS definition of failure to suppress morning serum cortisol concentration to less than 50 nmol/L after treatment with 1 mg oral dexamethasone at 11 p.m. the previous evening in those with no clinical features of CS.

Roughly half of patients (n = 649) showed normal cortisol suppression with dexamethasone, identifying them as having nonfunctioning adrenal tumors, and about 35% showed possible MACS based on having moderate levels of excess cortisol.

Nearly 11% (n = 140) showed definitive MACS with more robust cortisol levels, and 5% (n = 65) received a diagnosis of clinically overt CS despite selection criteria meant to exclude people with clinical signs of CS.

There was a clear relationship between patient sex and severity of autonomous cortisol production. Among those with nonfunctioning adrenal tumors, 64% were women, which rose to 74% women in those with definitive MACS and 86% women among those with CS. The median age of participants was 60 years old.
 

Increasing cortisol levels linked with cardiometabolic disease

Analysis of the prevalence of hypertension and type 2 diabetes after adjustment for age, sex, and body mass index showed that, compared with people with nonfunctioning adrenal tumors, those with definitive MACS had a significant 15% higher rate of hypertension and those with overt CS had a 37% higher rate. 

Higher levels of excess cortisol were also directly linked with an increased need for treatment with three or more antihypertensive agents to control blood pressure. Those with definitive MACS had a significant 31% higher rate of being on three or more drugs, and those with overt CS had a greater than twofold higher rate.

People with overt CS also had a significant 62% higher rate of type 2 diabetes, compared with those with a nonfunctioning tumor, but in those with definitive MACS the association was not significant. However, people with definitive MACS or overt CS who had type 2 diabetes and also had significantly increased rates of requiring insulin treatment.

The findings show that “people with definitive MACS carry an increased cardiometabolic burden similar to that seen in CS even if they do not display typical features of clinically overt cortisol excess,” the authors wrote in the report.

Even among those with apparently nonfunctioning tumors, each 10 nmol/L rise in cortisol level during a dexamethasone-suppression test was associated with a higher cardiometabolic disease burden. This observation suggests that current diagnostic cutoffs for the suppression test may miss some people with clinically relevant autonomous cortisol secretion, the report said. The study findings also suggest that people with benign adrenal tumors show a progressive continuum of excess cortisol with clinical consequences that increase as levels increase.
 

Determine the consequences of cortisol secretion

“These data clearly support the European Society of Endocrinology guideline recommendations that clinicians should determine precisely the cardiometabolic consequences of mild cortisol secretion in patients with adrenal lesions,” André Lacroix, MD, wrote in an accompanying editorial.

But Dr. Lacroix included some caveats. He noted the “potential pitfalls in relying on a single total serum cortisol value after the 1-mg dexamethasone test.” He also wondered whether the analysis used optimal cortisol values to distinguish patient subgroups.

Plus, “even in patients with nonfunctioning adrenal tumors the prevalence of diabetes and hypertension is higher than in the general population, raising concerns about the cardiometabolic consequences of barely detectable cortisol excess,” wrote Dr. Lacroix, an endocrinologist at the CHUM Research Center and professor of medicine at the University of Montreal.

The study received no commercial funding. Dr. Prete, Dr. Chambers, and Dr. Lacroix have reported no relevant financial relationships. Dr. Arlt is listed as an inventor on a patent on the use of steroid profiling as a biomarker tool for the differential diagnosis of adrenal tumors.

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

In more than 15% of people with benign adrenal tumors, the growths produce clinically relevant levels of serum cortisol that are significantly linked with an increased prevalence of hypertension and, in 5% of those with Cushing syndrome (CS), an increased prevalence of type 2 diabetes, based on data from more than 1,300 people with benign adrenal tumors, the largest reported prospective study of the disorder.

The study results showed that mild autonomous cortisol secretion (MACS) from benign adrenal tumors “is very frequent and is an important risk condition for high blood pressure and type 2 diabetes, especially in older women,” said Alessandro Prete, MD, lead author of the study which was published online Jan. 3, 2022, in Annals of Internal Medicine.

SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY/Getty Images

“The impact of MACS on high blood pressure and risk for type 2 diabetes has been underestimated until now,” said Dr. Prete, an endocrinologist at the University of Birmingham (England), in a written statement. 

Results from previous studies “suggested that MACS is associated with poor health. Our study is the largest to establish conclusively the extent of the risk and severity of high blood pressure and type 2 diabetes in patients with MACS,” said Wiebke Arlt, MD, DSc, senior author and director of the Institute of Metabolism & Systems Research at the University of Birmingham.

All patients found to have a benign adrenal tumor should undergo testing for MACS and have their blood pressure and glucose levels measured regularly, Dr. Arlt advised in the statement released by the University of Birmingham.
 

MACS more common than previously thought

The new findings show that MACS “is more common and may have a more negative impact on health than previously thought, including increasing the risk for type 2 diabetes,” commented Lucy Chambers, PhD, head of research communications at Diabetes UK. “The findings suggest that screening for MACS could help identify people – particularly women, in whom the condition was found to be more common – who may benefit from support to reduce their risk of type 2 diabetes.”

The study included 1,305 people with newly diagnosed, benign adrenal tumors greater than 1 cm, a subset of patients prospectively enrolled in a study with the primary purpose of validating a novel way to diagnose adrenocortical carcinomas. Patients underwent treatment in 2011-2016 at any of 14 tertiary centers in 11 countries.

Researchers used a MACS definition of failure to suppress morning serum cortisol concentration to less than 50 nmol/L after treatment with 1 mg oral dexamethasone at 11 p.m. the previous evening in those with no clinical features of CS.

Roughly half of patients (n = 649) showed normal cortisol suppression with dexamethasone, identifying them as having nonfunctioning adrenal tumors, and about 35% showed possible MACS based on having moderate levels of excess cortisol.

Nearly 11% (n = 140) showed definitive MACS with more robust cortisol levels, and 5% (n = 65) received a diagnosis of clinically overt CS despite selection criteria meant to exclude people with clinical signs of CS.

There was a clear relationship between patient sex and severity of autonomous cortisol production. Among those with nonfunctioning adrenal tumors, 64% were women, which rose to 74% women in those with definitive MACS and 86% women among those with CS. The median age of participants was 60 years old.
 

Increasing cortisol levels linked with cardiometabolic disease

Analysis of the prevalence of hypertension and type 2 diabetes after adjustment for age, sex, and body mass index showed that, compared with people with nonfunctioning adrenal tumors, those with definitive MACS had a significant 15% higher rate of hypertension and those with overt CS had a 37% higher rate. 

Higher levels of excess cortisol were also directly linked with an increased need for treatment with three or more antihypertensive agents to control blood pressure. Those with definitive MACS had a significant 31% higher rate of being on three or more drugs, and those with overt CS had a greater than twofold higher rate.

People with overt CS also had a significant 62% higher rate of type 2 diabetes, compared with those with a nonfunctioning tumor, but in those with definitive MACS the association was not significant. However, people with definitive MACS or overt CS who had type 2 diabetes and also had significantly increased rates of requiring insulin treatment.

The findings show that “people with definitive MACS carry an increased cardiometabolic burden similar to that seen in CS even if they do not display typical features of clinically overt cortisol excess,” the authors wrote in the report.

Even among those with apparently nonfunctioning tumors, each 10 nmol/L rise in cortisol level during a dexamethasone-suppression test was associated with a higher cardiometabolic disease burden. This observation suggests that current diagnostic cutoffs for the suppression test may miss some people with clinically relevant autonomous cortisol secretion, the report said. The study findings also suggest that people with benign adrenal tumors show a progressive continuum of excess cortisol with clinical consequences that increase as levels increase.
 

Determine the consequences of cortisol secretion

“These data clearly support the European Society of Endocrinology guideline recommendations that clinicians should determine precisely the cardiometabolic consequences of mild cortisol secretion in patients with adrenal lesions,” André Lacroix, MD, wrote in an accompanying editorial.

But Dr. Lacroix included some caveats. He noted the “potential pitfalls in relying on a single total serum cortisol value after the 1-mg dexamethasone test.” He also wondered whether the analysis used optimal cortisol values to distinguish patient subgroups.

Plus, “even in patients with nonfunctioning adrenal tumors the prevalence of diabetes and hypertension is higher than in the general population, raising concerns about the cardiometabolic consequences of barely detectable cortisol excess,” wrote Dr. Lacroix, an endocrinologist at the CHUM Research Center and professor of medicine at the University of Montreal.

The study received no commercial funding. Dr. Prete, Dr. Chambers, and Dr. Lacroix have reported no relevant financial relationships. Dr. Arlt is listed as an inventor on a patent on the use of steroid profiling as a biomarker tool for the differential diagnosis of adrenal tumors.

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

A CDC advisory panel recommended on Jan. 5 that 12- to 17-year-olds in the U.S. should get the Pfizer COVID-19 booster shot 5 months after a primary series of vaccinations.

The CDC had already said 16- and 17-year-olds “may” receive a Pfizer booster but the new recommendation adds the 12- to 15-year-old group and strengthens the “may” to “should” for 16- and 17-year-olds.

The committee voted 13-1 to recommend the booster for ages 12-17. CDC Director Rochelle Walensky, MD, must still approve the recommendation for it to take effect.

The vote comes after the FDA on Jan. 3 authorized the Pfizer vaccine booster dose for 12- to 15-year-olds.

The FDA action updated the authorization for the Pfizer vaccine, and the agency also shortened the recommended time between a second dose and the booster to 5 months or more (from 6 months). A third primary series dose is also now authorized for certain immunocompromised children between 5 and 11 years old. Full details are available in an FDA news release.

The CDC on Jan. 4 also backed the shortened time frame and a third primary series dose for some immunocompromised children 5-11 years old. But the CDC delayed a decision on a booster for 12- to 15-year-olds until it heard from its Advisory Committee on Immunization Practices on Jan. 5.

The decision came as school districts nationwide are wrestling with decisions of whether to keep schools open or revert to a virtual format as cases surge, and as pediatric COVID-19 cases and hospitalizations reach new highs.

The only dissenting vote came from Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University in Nashville, Tenn.

She said after the vote, “I am just fine with kids getting a booster. This is not me against all boosters. I just really want the U.S. to move forward with all kids.”

Dr. Talbot said earlier in the comment period, “If we divert our public health from the unvaccinated to the vaccinated, we are not going to make a big impact. Boosters are incredibly important but they won’t solve this problem of the crowded hospitals.”

She said vaccinating the unvaccinated must be the priority.

“If you are a parent out there who has not yet vaccinated your child because you have questions, please, please talk to a health care provider,” she said.

Among the 13 supporters of the recommendation was Oliver Brooks, MD, chief medical officer of Watts HealthCare Corporation in Los Angeles.

Dr. Brooks said extending the population for boosters is another tool in the toolbox.

“If it’s a hammer, we should hit that nail hard,” he said.

Sara Oliver, MD, ACIP’s lead for the COVID-19 work group, presented the case behind the recommendation.

She noted the soaring Omicron cases.

“As of Jan. 3, the 7-day average had reached an all-time high of nearly 500,000 cases,” Dr. Oliver noted.

Since this summer, she said, adolescents have had a higher rate of incidence than that of adults.

“The majority of COVID cases continue to occur among the unvaccinated,” she said, “with unvaccinated 12- to 17-year-olds having a 7-times-higher risk of testing positive for SARS-CoV-2 compared to vaccinated 12- to 17-year-olds. Unvaccinated 12- to 17-year-olds have around 11 times higher risk of hospitalization than vaccinated 12- to 17-year-olds.

“Vaccine effectiveness in adolescents 12-15 years old remains high,” Dr. Oliver said, but evidence shows there may be “some waning over time.”

Discussion of risk centered on myocarditis.

Dr. Oliver said myocarditis rates reported after the Pfizer vaccine in Israel across all populations as of Dec. 15 show that “the rates of myocarditis after a third dose are lower than what is seen after the second dose.”

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

A CDC advisory panel recommended on Jan. 5 that 12- to 17-year-olds in the U.S. should get the Pfizer COVID-19 booster shot 5 months after a primary series of vaccinations.

The CDC had already said 16- and 17-year-olds “may” receive a Pfizer booster but the new recommendation adds the 12- to 15-year-old group and strengthens the “may” to “should” for 16- and 17-year-olds.

The committee voted 13-1 to recommend the booster for ages 12-17. CDC Director Rochelle Walensky, MD, must still approve the recommendation for it to take effect.

The vote comes after the FDA on Jan. 3 authorized the Pfizer vaccine booster dose for 12- to 15-year-olds.

The FDA action updated the authorization for the Pfizer vaccine, and the agency also shortened the recommended time between a second dose and the booster to 5 months or more (from 6 months). A third primary series dose is also now authorized for certain immunocompromised children between 5 and 11 years old. Full details are available in an FDA news release.

The CDC on Jan. 4 also backed the shortened time frame and a third primary series dose for some immunocompromised children 5-11 years old. But the CDC delayed a decision on a booster for 12- to 15-year-olds until it heard from its Advisory Committee on Immunization Practices on Jan. 5.

The decision came as school districts nationwide are wrestling with decisions of whether to keep schools open or revert to a virtual format as cases surge, and as pediatric COVID-19 cases and hospitalizations reach new highs.

The only dissenting vote came from Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University in Nashville, Tenn.

She said after the vote, “I am just fine with kids getting a booster. This is not me against all boosters. I just really want the U.S. to move forward with all kids.”

Dr. Talbot said earlier in the comment period, “If we divert our public health from the unvaccinated to the vaccinated, we are not going to make a big impact. Boosters are incredibly important but they won’t solve this problem of the crowded hospitals.”

She said vaccinating the unvaccinated must be the priority.

“If you are a parent out there who has not yet vaccinated your child because you have questions, please, please talk to a health care provider,” she said.

Among the 13 supporters of the recommendation was Oliver Brooks, MD, chief medical officer of Watts HealthCare Corporation in Los Angeles.

Dr. Brooks said extending the population for boosters is another tool in the toolbox.

“If it’s a hammer, we should hit that nail hard,” he said.

Sara Oliver, MD, ACIP’s lead for the COVID-19 work group, presented the case behind the recommendation.

She noted the soaring Omicron cases.

“As of Jan. 3, the 7-day average had reached an all-time high of nearly 500,000 cases,” Dr. Oliver noted.

Since this summer, she said, adolescents have had a higher rate of incidence than that of adults.

“The majority of COVID cases continue to occur among the unvaccinated,” she said, “with unvaccinated 12- to 17-year-olds having a 7-times-higher risk of testing positive for SARS-CoV-2 compared to vaccinated 12- to 17-year-olds. Unvaccinated 12- to 17-year-olds have around 11 times higher risk of hospitalization than vaccinated 12- to 17-year-olds.

“Vaccine effectiveness in adolescents 12-15 years old remains high,” Dr. Oliver said, but evidence shows there may be “some waning over time.”

Discussion of risk centered on myocarditis.

Dr. Oliver said myocarditis rates reported after the Pfizer vaccine in Israel across all populations as of Dec. 15 show that “the rates of myocarditis after a third dose are lower than what is seen after the second dose.”

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

A CDC advisory panel recommended on Jan. 5 that 12- to 17-year-olds in the U.S. should get the Pfizer COVID-19 booster shot 5 months after a primary series of vaccinations.

The CDC had already said 16- and 17-year-olds “may” receive a Pfizer booster but the new recommendation adds the 12- to 15-year-old group and strengthens the “may” to “should” for 16- and 17-year-olds.

The committee voted 13-1 to recommend the booster for ages 12-17. CDC Director Rochelle Walensky, MD, must still approve the recommendation for it to take effect.

The vote comes after the FDA on Jan. 3 authorized the Pfizer vaccine booster dose for 12- to 15-year-olds.

The FDA action updated the authorization for the Pfizer vaccine, and the agency also shortened the recommended time between a second dose and the booster to 5 months or more (from 6 months). A third primary series dose is also now authorized for certain immunocompromised children between 5 and 11 years old. Full details are available in an FDA news release.

The CDC on Jan. 4 also backed the shortened time frame and a third primary series dose for some immunocompromised children 5-11 years old. But the CDC delayed a decision on a booster for 12- to 15-year-olds until it heard from its Advisory Committee on Immunization Practices on Jan. 5.

The decision came as school districts nationwide are wrestling with decisions of whether to keep schools open or revert to a virtual format as cases surge, and as pediatric COVID-19 cases and hospitalizations reach new highs.

The only dissenting vote came from Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University in Nashville, Tenn.

She said after the vote, “I am just fine with kids getting a booster. This is not me against all boosters. I just really want the U.S. to move forward with all kids.”

Dr. Talbot said earlier in the comment period, “If we divert our public health from the unvaccinated to the vaccinated, we are not going to make a big impact. Boosters are incredibly important but they won’t solve this problem of the crowded hospitals.”

She said vaccinating the unvaccinated must be the priority.

“If you are a parent out there who has not yet vaccinated your child because you have questions, please, please talk to a health care provider,” she said.

Among the 13 supporters of the recommendation was Oliver Brooks, MD, chief medical officer of Watts HealthCare Corporation in Los Angeles.

Dr. Brooks said extending the population for boosters is another tool in the toolbox.

“If it’s a hammer, we should hit that nail hard,” he said.

Sara Oliver, MD, ACIP’s lead for the COVID-19 work group, presented the case behind the recommendation.

She noted the soaring Omicron cases.

“As of Jan. 3, the 7-day average had reached an all-time high of nearly 500,000 cases,” Dr. Oliver noted.

Since this summer, she said, adolescents have had a higher rate of incidence than that of adults.

“The majority of COVID cases continue to occur among the unvaccinated,” she said, “with unvaccinated 12- to 17-year-olds having a 7-times-higher risk of testing positive for SARS-CoV-2 compared to vaccinated 12- to 17-year-olds. Unvaccinated 12- to 17-year-olds have around 11 times higher risk of hospitalization than vaccinated 12- to 17-year-olds.

“Vaccine effectiveness in adolescents 12-15 years old remains high,” Dr. Oliver said, but evidence shows there may be “some waning over time.”

Discussion of risk centered on myocarditis.

Dr. Oliver said myocarditis rates reported after the Pfizer vaccine in Israel across all populations as of Dec. 15 show that “the rates of myocarditis after a third dose are lower than what is seen after the second dose.”

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

If a fish can drive …

Have you ever seen a sparrow swim? Have you ever seen an elephant fly? How about a goldfish driving a car? Well, one of these is not just something out of a children’s book.

In a recent study, investigators from Ben-Gurion University did the impossible and got a fish to drive a robotic car on land. How?

PxHere

No, there wasn’t a tiny steering wheel inside the tank. The researchers created a tank with video recognition ability to sync with the fish. This video shows that the car, on which the tank sat, would navigate in the direction that the fish swam. The goal was to get the fish to “drive” toward a visual target, and with a little training the fish was successful regardless of start point, the researchers explained.

So what does that tell us about the brain and behavior? Shachar Givon, who was part of the research team, said the “study hints that navigational ability is universal rather than specific to the environment.”

The study’s domain transfer methodology (putting one species in the environment of another and have them cope with an unfamiliar task) shows that other animals also have the cognitive ability to transfer skills from one terrestrial environment to another.

That leads us to lesson two. Goldfish are much smarter than we think. So please don’t tap on the glass.
 

We prefer ‘It’s not writing a funny LOTME article’!

So many medical journals spend all their time grappling with such silly dilemmas as curing cancer or beating COVID-19. Boring! Fortunately, the BMJ dares to stand above the rest by dedicating its Christmas issue to answering the real issues in medicine. And what was the biggest question? Which is the more accurate idiom: “It’s not rocket science,” or “It’s not brain surgery”?

Tumisu/Pixabay

English researchers collected data from 329 aerospace engineers and 72 neurosurgeons who took the Great British Intelligence Test and compared the results against 18,000 people in the general public.

The engineers and neurosurgeons were basically identical in four of the six domains, but neurosurgeons had the advantage when it came to semantic problem solving and engineers had an edge at mental manipulation and attention. The aerospace engineers were identical to the public in all domains, but neurosurgeons held an advantage in problem-solving speed and a disadvantage in memory recall speed.

The researchers noted that exposure to Latin and Greek etymologies during their education gave neurosurgeons the advantage in semantic problem solving, while the aerospace engineers’ advantage in mental manipulation stems from skills taught during engineering training.

But is there a definitive answer to the question? If you’ve got an easy task in front of you, which is more accurate to say: “It’s not rocket science” or “It’s not brain surgery”? Can we get a drum roll?

It’s not brain surgery! At least, as long as the task doesn’t involve rapid problem solving. The investigators hedged further by saying that “It’s a walk in the park” is probably more accurate. Plus, “other specialties might deserve to be on that pedestal, and future work should aim to determine the most deserving profession,” they wrote. Well, at least we’ve got something to look forward to in BMJ’s next Christmas issue.
 

For COVID-19, a syringe is the sheep of things to come

The logical approach to fighting COVID-19 hasn’t really worked with a lot of people, so how about something more emotional?

ChiemSeherin/Pixabay

People love animals, so they might be a good way to promote the use of vaccines and masks. Puppies are awfully cute, and so are koalas and pandas. And who can say no to a sea otter?

Well, forget it. Instead, we’ve got elephants … and sheep … and goats. Oh my.

First, elephant Santas. The Jirasartwitthaya school in Ayutthaya, Thailand, was recently visited by five elephants in Santa Claus costumes who handed out hand sanitizer and face masks to the students, Reuters said.

“I’m so glad that I got a balloon from the elephant. My heart is pounding very fast,” student Biuon Greham said. And balloons. The elephants handed out sanitizer and masks and balloons. There’s a sentence we never thought we’d write.

And those sheep and goats we mentioned? That was a different party.

Hanspeter Etzold, who “works with shepherds, companies, and animals to run team-building events in the northern German town of Schneverdingen,” according to Reuters, had an idea to promote the use of the COVID-19 vaccine. And yes, it involved sheep and goats.

Mr. Etzold worked with shepherd Wiebke Schmidt-Kochan, who arranged her 700 goats and sheep into the shape of a 100-meter-long syringe using bits of bread laying on the ground. “Sheep are such likable animals – maybe they can get the message over better,” Mr. Etzold told AP.

If those are the carrots in an animals-as-carrots-and-sticks approach, then maybe this golf-club-chomping crab could be the stick. We’re certainly not going to argue with it.
 

To be or not to be … seen

Increased Zoom meetings have been another side effect of the COVID-19 pandemic as more and more people have been working and learning from home.

filadendron/E+

If a fish can drive …

Have you ever seen a sparrow swim? Have you ever seen an elephant fly? How about a goldfish driving a car? Well, one of these is not just something out of a children’s book.

In a recent study, investigators from Ben-Gurion University did the impossible and got a fish to drive a robotic car on land. How?

PxHere

No, there wasn’t a tiny steering wheel inside the tank. The researchers created a tank with video recognition ability to sync with the fish. This video shows that the car, on which the tank sat, would navigate in the direction that the fish swam. The goal was to get the fish to “drive” toward a visual target, and with a little training the fish was successful regardless of start point, the researchers explained.

So what does that tell us about the brain and behavior? Shachar Givon, who was part of the research team, said the “study hints that navigational ability is universal rather than specific to the environment.”

The study’s domain transfer methodology (putting one species in the environment of another and have them cope with an unfamiliar task) shows that other animals also have the cognitive ability to transfer skills from one terrestrial environment to another.

That leads us to lesson two. Goldfish are much smarter than we think. So please don’t tap on the glass.
 

We prefer ‘It’s not writing a funny LOTME article’!

So many medical journals spend all their time grappling with such silly dilemmas as curing cancer or beating COVID-19. Boring! Fortunately, the BMJ dares to stand above the rest by dedicating its Christmas issue to answering the real issues in medicine. And what was the biggest question? Which is the more accurate idiom: “It’s not rocket science,” or “It’s not brain surgery”?

Tumisu/Pixabay

English researchers collected data from 329 aerospace engineers and 72 neurosurgeons who took the Great British Intelligence Test and compared the results against 18,000 people in the general public.

The engineers and neurosurgeons were basically identical in four of the six domains, but neurosurgeons had the advantage when it came to semantic problem solving and engineers had an edge at mental manipulation and attention. The aerospace engineers were identical to the public in all domains, but neurosurgeons held an advantage in problem-solving speed and a disadvantage in memory recall speed.

The researchers noted that exposure to Latin and Greek etymologies during their education gave neurosurgeons the advantage in semantic problem solving, while the aerospace engineers’ advantage in mental manipulation stems from skills taught during engineering training.

But is there a definitive answer to the question? If you’ve got an easy task in front of you, which is more accurate to say: “It’s not rocket science” or “It’s not brain surgery”? Can we get a drum roll?

It’s not brain surgery! At least, as long as the task doesn’t involve rapid problem solving. The investigators hedged further by saying that “It’s a walk in the park” is probably more accurate. Plus, “other specialties might deserve to be on that pedestal, and future work should aim to determine the most deserving profession,” they wrote. Well, at least we’ve got something to look forward to in BMJ’s next Christmas issue.
 

For COVID-19, a syringe is the sheep of things to come

The logical approach to fighting COVID-19 hasn’t really worked with a lot of people, so how about something more emotional?

ChiemSeherin/Pixabay

People love animals, so they might be a good way to promote the use of vaccines and masks. Puppies are awfully cute, and so are koalas and pandas. And who can say no to a sea otter?

Well, forget it. Instead, we’ve got elephants … and sheep … and goats. Oh my.

First, elephant Santas. The Jirasartwitthaya school in Ayutthaya, Thailand, was recently visited by five elephants in Santa Claus costumes who handed out hand sanitizer and face masks to the students, Reuters said.

“I’m so glad that I got a balloon from the elephant. My heart is pounding very fast,” student Biuon Greham said. And balloons. The elephants handed out sanitizer and masks and balloons. There’s a sentence we never thought we’d write.

And those sheep and goats we mentioned? That was a different party.

Hanspeter Etzold, who “works with shepherds, companies, and animals to run team-building events in the northern German town of Schneverdingen,” according to Reuters, had an idea to promote the use of the COVID-19 vaccine. And yes, it involved sheep and goats.

Mr. Etzold worked with shepherd Wiebke Schmidt-Kochan, who arranged her 700 goats and sheep into the shape of a 100-meter-long syringe using bits of bread laying on the ground. “Sheep are such likable animals – maybe they can get the message over better,” Mr. Etzold told AP.

If those are the carrots in an animals-as-carrots-and-sticks approach, then maybe this golf-club-chomping crab could be the stick. We’re certainly not going to argue with it.
 

To be or not to be … seen

Increased Zoom meetings have been another side effect of the COVID-19 pandemic as more and more people have been working and learning from home.

filadendron/E+

If a fish can drive …

Have you ever seen a sparrow swim? Have you ever seen an elephant fly? How about a goldfish driving a car? Well, one of these is not just something out of a children’s book.

In a recent study, investigators from Ben-Gurion University did the impossible and got a fish to drive a robotic car on land. How?

PxHere

No, there wasn’t a tiny steering wheel inside the tank. The researchers created a tank with video recognition ability to sync with the fish. This video shows that the car, on which the tank sat, would navigate in the direction that the fish swam. The goal was to get the fish to “drive” toward a visual target, and with a little training the fish was successful regardless of start point, the researchers explained.

So what does that tell us about the brain and behavior? Shachar Givon, who was part of the research team, said the “study hints that navigational ability is universal rather than specific to the environment.”

The study’s domain transfer methodology (putting one species in the environment of another and have them cope with an unfamiliar task) shows that other animals also have the cognitive ability to transfer skills from one terrestrial environment to another.

That leads us to lesson two. Goldfish are much smarter than we think. So please don’t tap on the glass.
 

We prefer ‘It’s not writing a funny LOTME article’!

So many medical journals spend all their time grappling with such silly dilemmas as curing cancer or beating COVID-19. Boring! Fortunately, the BMJ dares to stand above the rest by dedicating its Christmas issue to answering the real issues in medicine. And what was the biggest question? Which is the more accurate idiom: “It’s not rocket science,” or “It’s not brain surgery”?

Tumisu/Pixabay

English researchers collected data from 329 aerospace engineers and 72 neurosurgeons who took the Great British Intelligence Test and compared the results against 18,000 people in the general public.

The engineers and neurosurgeons were basically identical in four of the six domains, but neurosurgeons had the advantage when it came to semantic problem solving and engineers had an edge at mental manipulation and attention. The aerospace engineers were identical to the public in all domains, but neurosurgeons held an advantage in problem-solving speed and a disadvantage in memory recall speed.

The researchers noted that exposure to Latin and Greek etymologies during their education gave neurosurgeons the advantage in semantic problem solving, while the aerospace engineers’ advantage in mental manipulation stems from skills taught during engineering training.

But is there a definitive answer to the question? If you’ve got an easy task in front of you, which is more accurate to say: “It’s not rocket science” or “It’s not brain surgery”? Can we get a drum roll?

It’s not brain surgery! At least, as long as the task doesn’t involve rapid problem solving. The investigators hedged further by saying that “It’s a walk in the park” is probably more accurate. Plus, “other specialties might deserve to be on that pedestal, and future work should aim to determine the most deserving profession,” they wrote. Well, at least we’ve got something to look forward to in BMJ’s next Christmas issue.
 

For COVID-19, a syringe is the sheep of things to come

The logical approach to fighting COVID-19 hasn’t really worked with a lot of people, so how about something more emotional?

ChiemSeherin/Pixabay

People love animals, so they might be a good way to promote the use of vaccines and masks. Puppies are awfully cute, and so are koalas and pandas. And who can say no to a sea otter?

Well, forget it. Instead, we’ve got elephants … and sheep … and goats. Oh my.

First, elephant Santas. The Jirasartwitthaya school in Ayutthaya, Thailand, was recently visited by five elephants in Santa Claus costumes who handed out hand sanitizer and face masks to the students, Reuters said.

“I’m so glad that I got a balloon from the elephant. My heart is pounding very fast,” student Biuon Greham said. And balloons. The elephants handed out sanitizer and masks and balloons. There’s a sentence we never thought we’d write.

And those sheep and goats we mentioned? That was a different party.

Hanspeter Etzold, who “works with shepherds, companies, and animals to run team-building events in the northern German town of Schneverdingen,” according to Reuters, had an idea to promote the use of the COVID-19 vaccine. And yes, it involved sheep and goats.

Mr. Etzold worked with shepherd Wiebke Schmidt-Kochan, who arranged her 700 goats and sheep into the shape of a 100-meter-long syringe using bits of bread laying on the ground. “Sheep are such likable animals – maybe they can get the message over better,” Mr. Etzold told AP.

If those are the carrots in an animals-as-carrots-and-sticks approach, then maybe this golf-club-chomping crab could be the stick. We’re certainly not going to argue with it.
 

To be or not to be … seen

Increased Zoom meetings have been another side effect of the COVID-19 pandemic as more and more people have been working and learning from home.

filadendron/E+