Key clinical point: Combination of bevacizumab with S-1 and irinotecan vs 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6)/capecitabine and oxaliplatin (CapeOX) as the first-line treatment for metastatic colorectal cancer (mCRC) showed comparable overall survival and noninferior progression-free survival (PFS).

Major finding: During a median follow-up of 48.7 months, median survival and PFS in patients assigned to bevacizumab+mFOLFOX6/CapeOX vs bevacizumab+S-1/irinotecan were 32.6 months vs 34.3 months (hazard ratio [HR], 0.89; P = .293) and 10.8 months vs 14.0 months (HR, 0.86; P less than .0001 for noninferiority), respectively. Safety results were as reported previously.

Study details: Findings are from phase 3 TRICOLORE trial including 487 patients with previously untreated mCRC who were randomly assigned to receive bevacizumab+mFOLFOX6/CapeOX or bevacizumab+S-1 and irinotecan.

Disclosures: This study was funded by Tokyo Cooperative Oncology Group with funding from Taiho Pharmaceutical Co. Ltd., Japan. Some of the authors including the lead author declared receiving honoraria, research funding, and/or consulting fees from various sources.

Source: Denda T et al. Eur J Cancer. 2021 Jul 22. doi: 10.1016/j.ejca.2021.06.013.

Key clinical point: Combination of bevacizumab with S-1 and irinotecan vs 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6)/capecitabine and oxaliplatin (CapeOX) as the first-line treatment for metastatic colorectal cancer (mCRC) showed comparable overall survival and noninferior progression-free survival (PFS).

Major finding: During a median follow-up of 48.7 months, median survival and PFS in patients assigned to bevacizumab+mFOLFOX6/CapeOX vs bevacizumab+S-1/irinotecan were 32.6 months vs 34.3 months (hazard ratio [HR], 0.89; P = .293) and 10.8 months vs 14.0 months (HR, 0.86; P less than .0001 for noninferiority), respectively. Safety results were as reported previously.

Study details: Findings are from phase 3 TRICOLORE trial including 487 patients with previously untreated mCRC who were randomly assigned to receive bevacizumab+mFOLFOX6/CapeOX or bevacizumab+S-1 and irinotecan.

Disclosures: This study was funded by Tokyo Cooperative Oncology Group with funding from Taiho Pharmaceutical Co. Ltd., Japan. Some of the authors including the lead author declared receiving honoraria, research funding, and/or consulting fees from various sources.

Source: Denda T et al. Eur J Cancer. 2021 Jul 22. doi: 10.1016/j.ejca.2021.06.013.

Key clinical point: Combination of bevacizumab with S-1 and irinotecan vs 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6)/capecitabine and oxaliplatin (CapeOX) as the first-line treatment for metastatic colorectal cancer (mCRC) showed comparable overall survival and noninferior progression-free survival (PFS).

Major finding: During a median follow-up of 48.7 months, median survival and PFS in patients assigned to bevacizumab+mFOLFOX6/CapeOX vs bevacizumab+S-1/irinotecan were 32.6 months vs 34.3 months (hazard ratio [HR], 0.89; P = .293) and 10.8 months vs 14.0 months (HR, 0.86; P less than .0001 for noninferiority), respectively. Safety results were as reported previously.

Study details: Findings are from phase 3 TRICOLORE trial including 487 patients with previously untreated mCRC who were randomly assigned to receive bevacizumab+mFOLFOX6/CapeOX or bevacizumab+S-1 and irinotecan.

Disclosures: This study was funded by Tokyo Cooperative Oncology Group with funding from Taiho Pharmaceutical Co. Ltd., Japan. Some of the authors including the lead author declared receiving honoraria, research funding, and/or consulting fees from various sources.

Source: Denda T et al. Eur J Cancer. 2021 Jul 22. doi: 10.1016/j.ejca.2021.06.013.

Key clinical point: Sequential vs concurrent administration of bevacizumab and chemotherapy failed to improve objective response rate (ORR) in patients with metastatic colorectal cancer (mCRC), but was associated with survival advantage and fewer adverse effects.

Major finding: ORR (odds ratio, 0.96; P = .89) was not significantly different among patients who received bevacizumab and chemotherapy concurrently or sequentially. However, sequential administration was associated with survival benefit (adjusted hazard ratio, 0.73; P = .04), significantly reduced rates of severe diarrhea (5.3% vs 16.5%; P = .006), and improved physical functioning at cycle 12 (P = .02).

Study details: Findings are from OBELICS, a phase 3 trial including 230 patients with unresectable, previously untreated, or single line-treated mCRC who were randomly assigned to receive 12 biweekly cycles of standard oxaliplatin-based regimens and bevacizumab administered either concurrently with chemotherapy or sequentially (4 days before chemotherapy).

Disclosures: The trial was supported by the Italian Ministry of Health. Some of the authors reported receiving personal fees, research grants, consulting or advisory fees, and/or nonfinancial support from various sources.

Source: Avallone A et al. JAMA Netw Open. 2021 Jul 26. doi: 10.1001/jamanetworkopen.2021.18475.

Key clinical point: Sequential vs concurrent administration of bevacizumab and chemotherapy failed to improve objective response rate (ORR) in patients with metastatic colorectal cancer (mCRC), but was associated with survival advantage and fewer adverse effects.

Major finding: ORR (odds ratio, 0.96; P = .89) was not significantly different among patients who received bevacizumab and chemotherapy concurrently or sequentially. However, sequential administration was associated with survival benefit (adjusted hazard ratio, 0.73; P = .04), significantly reduced rates of severe diarrhea (5.3% vs 16.5%; P = .006), and improved physical functioning at cycle 12 (P = .02).

Study details: Findings are from OBELICS, a phase 3 trial including 230 patients with unresectable, previously untreated, or single line-treated mCRC who were randomly assigned to receive 12 biweekly cycles of standard oxaliplatin-based regimens and bevacizumab administered either concurrently with chemotherapy or sequentially (4 days before chemotherapy).

Disclosures: The trial was supported by the Italian Ministry of Health. Some of the authors reported receiving personal fees, research grants, consulting or advisory fees, and/or nonfinancial support from various sources.

Source: Avallone A et al. JAMA Netw Open. 2021 Jul 26. doi: 10.1001/jamanetworkopen.2021.18475.

Key clinical point: Sequential vs concurrent administration of bevacizumab and chemotherapy failed to improve objective response rate (ORR) in patients with metastatic colorectal cancer (mCRC), but was associated with survival advantage and fewer adverse effects.

Major finding: ORR (odds ratio, 0.96; P = .89) was not significantly different among patients who received bevacizumab and chemotherapy concurrently or sequentially. However, sequential administration was associated with survival benefit (adjusted hazard ratio, 0.73; P = .04), significantly reduced rates of severe diarrhea (5.3% vs 16.5%; P = .006), and improved physical functioning at cycle 12 (P = .02).

Study details: Findings are from OBELICS, a phase 3 trial including 230 patients with unresectable, previously untreated, or single line-treated mCRC who were randomly assigned to receive 12 biweekly cycles of standard oxaliplatin-based regimens and bevacizumab administered either concurrently with chemotherapy or sequentially (4 days before chemotherapy).

Disclosures: The trial was supported by the Italian Ministry of Health. Some of the authors reported receiving personal fees, research grants, consulting or advisory fees, and/or nonfinancial support from various sources.

Source: Avallone A et al. JAMA Netw Open. 2021 Jul 26. doi: 10.1001/jamanetworkopen.2021.18475.

Key clinical point: High mesothelin (MSLN) expression in stage IV colorectal cancer (CRC) was associated with chemoresistant properties and poor prognoses.

Major finding: Patients with high vs low MSLN expression had a low objective response rate (22.0% vs 45.5%; P = .0050), disease control rate (65.9% vs 85.9%; P = .0019), and higher rates of progressive disease (31.0% vs 13.5%; P = .028). The rates of 12-month progression-free survival and 3-year overall survival in high vs low MSNL expression group were 20.0% vs 44.1% (P = .0120) and 23.5% vs 41.5% (P = .0120), respectively.

Study details: Findings are from a retrospective analysis of 254 patients with stage IV CRC who received systemic chemotherapy following primary tumor resection between 2000 and 2019.

Disclosures: The study received no financial or material support. The authors declared no conflict of interests related to this article.

Source: Nagata K et al. Ann Surg Oncol. 2021 Jul 27. doi: 10.1245/s10434-021-10507-y.

Key clinical point: High mesothelin (MSLN) expression in stage IV colorectal cancer (CRC) was associated with chemoresistant properties and poor prognoses.

Major finding: Patients with high vs low MSLN expression had a low objective response rate (22.0% vs 45.5%; P = .0050), disease control rate (65.9% vs 85.9%; P = .0019), and higher rates of progressive disease (31.0% vs 13.5%; P = .028). The rates of 12-month progression-free survival and 3-year overall survival in high vs low MSNL expression group were 20.0% vs 44.1% (P = .0120) and 23.5% vs 41.5% (P = .0120), respectively.

Study details: Findings are from a retrospective analysis of 254 patients with stage IV CRC who received systemic chemotherapy following primary tumor resection between 2000 and 2019.

Disclosures: The study received no financial or material support. The authors declared no conflict of interests related to this article.

Source: Nagata K et al. Ann Surg Oncol. 2021 Jul 27. doi: 10.1245/s10434-021-10507-y.

Key clinical point: High mesothelin (MSLN) expression in stage IV colorectal cancer (CRC) was associated with chemoresistant properties and poor prognoses.

Major finding: Patients with high vs low MSLN expression had a low objective response rate (22.0% vs 45.5%; P = .0050), disease control rate (65.9% vs 85.9%; P = .0019), and higher rates of progressive disease (31.0% vs 13.5%; P = .028). The rates of 12-month progression-free survival and 3-year overall survival in high vs low MSNL expression group were 20.0% vs 44.1% (P = .0120) and 23.5% vs 41.5% (P = .0120), respectively.

Study details: Findings are from a retrospective analysis of 254 patients with stage IV CRC who received systemic chemotherapy following primary tumor resection between 2000 and 2019.

Disclosures: The study received no financial or material support. The authors declared no conflict of interests related to this article.

Source: Nagata K et al. Ann Surg Oncol. 2021 Jul 27. doi: 10.1245/s10434-021-10507-y.

Key clinical point: Under real-life settings, aflibercept-FOLFIRI appeared to be a feasible second-line treatment for metastatic colorectal cancer (mCRC) with progression-free survival (PFS) of more than 12 months in the first-line therapy being the only predictive marker for better survival.

Major finding: Overall, the median overall survival and PFS was 13 (95% confidence interval [CI], 10-18) months and 6 (95% CI, 5-7) months, respectively. The overall response rate and disease control rate were 12.3% and 49.1%, respectively. The PFS of more than 12 months in the first-line chemotherapy was associated with better survival (hazard ratio, 0.32; P = .01). Most nonhematological malignancies were grade 1 or 2, whereas hypertension (18.4%) and venous thromboembolism (16.3%) were the most commonly reported grade 3-4 adverse events.

Study details: Findings are from a retrospective analysis of 49 patients with mCRC who progressed after first-line oxaliplatin-based chemotherapy and received second-line treatment with aflibercept in combination with FOLFIRI.

Disclosures: The study received no external funding. The authors declared no conflict of interests.

Source: Lavacchi D et al. Cancers (Basel). 2021 Jul 31. doi: 10.3390/cancers13153863.

Key clinical point: Under real-life settings, aflibercept-FOLFIRI appeared to be a feasible second-line treatment for metastatic colorectal cancer (mCRC) with progression-free survival (PFS) of more than 12 months in the first-line therapy being the only predictive marker for better survival.

Major finding: Overall, the median overall survival and PFS was 13 (95% confidence interval [CI], 10-18) months and 6 (95% CI, 5-7) months, respectively. The overall response rate and disease control rate were 12.3% and 49.1%, respectively. The PFS of more than 12 months in the first-line chemotherapy was associated with better survival (hazard ratio, 0.32; P = .01). Most nonhematological malignancies were grade 1 or 2, whereas hypertension (18.4%) and venous thromboembolism (16.3%) were the most commonly reported grade 3-4 adverse events.

Study details: Findings are from a retrospective analysis of 49 patients with mCRC who progressed after first-line oxaliplatin-based chemotherapy and received second-line treatment with aflibercept in combination with FOLFIRI.

Disclosures: The study received no external funding. The authors declared no conflict of interests.

Source: Lavacchi D et al. Cancers (Basel). 2021 Jul 31. doi: 10.3390/cancers13153863.

Key clinical point: Under real-life settings, aflibercept-FOLFIRI appeared to be a feasible second-line treatment for metastatic colorectal cancer (mCRC) with progression-free survival (PFS) of more than 12 months in the first-line therapy being the only predictive marker for better survival.

Major finding: Overall, the median overall survival and PFS was 13 (95% confidence interval [CI], 10-18) months and 6 (95% CI, 5-7) months, respectively. The overall response rate and disease control rate were 12.3% and 49.1%, respectively. The PFS of more than 12 months in the first-line chemotherapy was associated with better survival (hazard ratio, 0.32; P = .01). Most nonhematological malignancies were grade 1 or 2, whereas hypertension (18.4%) and venous thromboembolism (16.3%) were the most commonly reported grade 3-4 adverse events.

Study details: Findings are from a retrospective analysis of 49 patients with mCRC who progressed after first-line oxaliplatin-based chemotherapy and received second-line treatment with aflibercept in combination with FOLFIRI.

Disclosures: The study received no external funding. The authors declared no conflict of interests.

Source: Lavacchi D et al. Cancers (Basel). 2021 Jul 31. doi: 10.3390/cancers13153863.

Key clinical point: Tumor deposits (TDs) are associated with a worse prognosis, thereby indicating that the addition of number of TDs to lymph node metastases count could improve prognostication accuracy in stage III colon cancer.

Major finding: The presence of TD was associated with poorer disease-free survival (DFS; hazard ratio [HR], 1.63; P < .0001) and overall survival (OS; HR, 1.59; P = .0004). Combining TD and number of lymph node metastases restaged 7.1% of pN1 patients as pN2 who had worse rates of 3-year DFS (80.5% vs 65.4%; P = .0003) and 5-year OS (87.9% vs 69.1%; P = .0001) vs those who remained classified as pN1.

Study details: Findings are from a post hoc analysis of CALGB/SWOG 80702 phase 3 trial involving 2,028 patients with stage III colon cancers. Overall, 74% of patients had TD-positive tumors.

Disclosures: This work was supported by the National Cancer Institute of the National Institutes of Health and in part by funds from Pfizer. R Cohen declared receiving honoraria and research grants from various sources.

Source: Cohen R et al. Ann Oncol. 2021 Jul 19. doi: 10.1016/j.annonc.2021.07.009.

Key clinical point: Tumor deposits (TDs) are associated with a worse prognosis, thereby indicating that the addition of number of TDs to lymph node metastases count could improve prognostication accuracy in stage III colon cancer.

Major finding: The presence of TD was associated with poorer disease-free survival (DFS; hazard ratio [HR], 1.63; P < .0001) and overall survival (OS; HR, 1.59; P = .0004). Combining TD and number of lymph node metastases restaged 7.1% of pN1 patients as pN2 who had worse rates of 3-year DFS (80.5% vs 65.4%; P = .0003) and 5-year OS (87.9% vs 69.1%; P = .0001) vs those who remained classified as pN1.

Study details: Findings are from a post hoc analysis of CALGB/SWOG 80702 phase 3 trial involving 2,028 patients with stage III colon cancers. Overall, 74% of patients had TD-positive tumors.

Disclosures: This work was supported by the National Cancer Institute of the National Institutes of Health and in part by funds from Pfizer. R Cohen declared receiving honoraria and research grants from various sources.

Source: Cohen R et al. Ann Oncol. 2021 Jul 19. doi: 10.1016/j.annonc.2021.07.009.

Key clinical point: Tumor deposits (TDs) are associated with a worse prognosis, thereby indicating that the addition of number of TDs to lymph node metastases count could improve prognostication accuracy in stage III colon cancer.

Major finding: The presence of TD was associated with poorer disease-free survival (DFS; hazard ratio [HR], 1.63; P < .0001) and overall survival (OS; HR, 1.59; P = .0004). Combining TD and number of lymph node metastases restaged 7.1% of pN1 patients as pN2 who had worse rates of 3-year DFS (80.5% vs 65.4%; P = .0003) and 5-year OS (87.9% vs 69.1%; P = .0001) vs those who remained classified as pN1.

Study details: Findings are from a post hoc analysis of CALGB/SWOG 80702 phase 3 trial involving 2,028 patients with stage III colon cancers. Overall, 74% of patients had TD-positive tumors.

Disclosures: This work was supported by the National Cancer Institute of the National Institutes of Health and in part by funds from Pfizer. R Cohen declared receiving honoraria and research grants from various sources.

Source: Cohen R et al. Ann Oncol. 2021 Jul 19. doi: 10.1016/j.annonc.2021.07.009.

Key clinical point: Patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) with liver metastasis showed resistance to programmed cell death receptor 1/programmed death ligand 1 (PD-1/PD-L1) inhibition, whereas those without liver involvement may derive clinical benefit.

Major finding: Patients without vs with liver metastases had a significantly superior objective response rate (19.5% vs 0.0%; P less than .001) and median progression-free survival (PFS; 4.0 months vs 1.5 months; P less than .001). Liver metastasis at the time of initiation of PD-1/PD-L1 therapy was the most significant factor associated with worse PFS (hazard ratio, 7.00; P < .001).

Study details: Findings are from a retrospective cohort study of 95 patients with MSS mCRC who received PD-1/PD-L1–targeting therapy after progression with prior standard chemotherapy.

Disclosures: No source of funding was declared. Dr. Fakih reported receiving honoraria and research funding and serving as an advisor and on the speakers’ bureau for various sources. No other disclosures were reported.

Source: Wang C et al. JAMA Netw Open. 2021 Aug 9. doi: 10.1001/jamanetworkopen.2021.18416.

Key clinical point: Patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) with liver metastasis showed resistance to programmed cell death receptor 1/programmed death ligand 1 (PD-1/PD-L1) inhibition, whereas those without liver involvement may derive clinical benefit.

Major finding: Patients without vs with liver metastases had a significantly superior objective response rate (19.5% vs 0.0%; P less than .001) and median progression-free survival (PFS; 4.0 months vs 1.5 months; P less than .001). Liver metastasis at the time of initiation of PD-1/PD-L1 therapy was the most significant factor associated with worse PFS (hazard ratio, 7.00; P < .001).

Study details: Findings are from a retrospective cohort study of 95 patients with MSS mCRC who received PD-1/PD-L1–targeting therapy after progression with prior standard chemotherapy.

Disclosures: No source of funding was declared. Dr. Fakih reported receiving honoraria and research funding and serving as an advisor and on the speakers’ bureau for various sources. No other disclosures were reported.

Source: Wang C et al. JAMA Netw Open. 2021 Aug 9. doi: 10.1001/jamanetworkopen.2021.18416.

Key clinical point: Patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) with liver metastasis showed resistance to programmed cell death receptor 1/programmed death ligand 1 (PD-1/PD-L1) inhibition, whereas those without liver involvement may derive clinical benefit.

Major finding: Patients without vs with liver metastases had a significantly superior objective response rate (19.5% vs 0.0%; P less than .001) and median progression-free survival (PFS; 4.0 months vs 1.5 months; P less than .001). Liver metastasis at the time of initiation of PD-1/PD-L1 therapy was the most significant factor associated with worse PFS (hazard ratio, 7.00; P < .001).

Study details: Findings are from a retrospective cohort study of 95 patients with MSS mCRC who received PD-1/PD-L1–targeting therapy after progression with prior standard chemotherapy.

Disclosures: No source of funding was declared. Dr. Fakih reported receiving honoraria and research funding and serving as an advisor and on the speakers’ bureau for various sources. No other disclosures were reported.

Source: Wang C et al. JAMA Netw Open. 2021 Aug 9. doi: 10.1001/jamanetworkopen.2021.18416.

Key clinical point: Computer-aided detection (CADe) has higher rates of colorectal neoplasia detection than other advanced endoscopic techniques like chromoendoscopy or mucosal visualization tools.

Major finding: The magnitude of increase in adenoma detection rate was higher with CADe vs chromoendoscopy (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.14-1.85) or with increased mucosal visualization systems (OR, 1.54; 95% CI, 1.22-1.94). Compared with high-definition white-light endoscopy, only CADe showed a significant increase in the detection of large adenomas (OR, 1.69; 95% CI, 1.10-2.60).

Study details: Findings are from a systematic review and meta-analysis of 50 randomized control trials including 34,445 participants who underwent colonoscopy.

Disclosures: There was no source of funding for this study. Some of the authors declared receiving consulting fees from Olympus, Medtronic, Fuji, Boston, Aries Pharmaceutical, Braintree Laboratories, Norgine, Endokey, and GI Supply.

Source: Spadaccini M et al. Lancet Gastroenterol Hepatol. 2021 Aug 4. doi: 10.1016/S2468-1253(21)00215-6.  

Key clinical point: Computer-aided detection (CADe) has higher rates of colorectal neoplasia detection than other advanced endoscopic techniques like chromoendoscopy or mucosal visualization tools.

Major finding: The magnitude of increase in adenoma detection rate was higher with CADe vs chromoendoscopy (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.14-1.85) or with increased mucosal visualization systems (OR, 1.54; 95% CI, 1.22-1.94). Compared with high-definition white-light endoscopy, only CADe showed a significant increase in the detection of large adenomas (OR, 1.69; 95% CI, 1.10-2.60).

Study details: Findings are from a systematic review and meta-analysis of 50 randomized control trials including 34,445 participants who underwent colonoscopy.

Disclosures: There was no source of funding for this study. Some of the authors declared receiving consulting fees from Olympus, Medtronic, Fuji, Boston, Aries Pharmaceutical, Braintree Laboratories, Norgine, Endokey, and GI Supply.

Source: Spadaccini M et al. Lancet Gastroenterol Hepatol. 2021 Aug 4. doi: 10.1016/S2468-1253(21)00215-6.  

Key clinical point: Computer-aided detection (CADe) has higher rates of colorectal neoplasia detection than other advanced endoscopic techniques like chromoendoscopy or mucosal visualization tools.

Major finding: The magnitude of increase in adenoma detection rate was higher with CADe vs chromoendoscopy (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.14-1.85) or with increased mucosal visualization systems (OR, 1.54; 95% CI, 1.22-1.94). Compared with high-definition white-light endoscopy, only CADe showed a significant increase in the detection of large adenomas (OR, 1.69; 95% CI, 1.10-2.60).

Study details: Findings are from a systematic review and meta-analysis of 50 randomized control trials including 34,445 participants who underwent colonoscopy.

Disclosures: There was no source of funding for this study. Some of the authors declared receiving consulting fees from Olympus, Medtronic, Fuji, Boston, Aries Pharmaceutical, Braintree Laboratories, Norgine, Endokey, and GI Supply.

Source: Spadaccini M et al. Lancet Gastroenterol Hepatol. 2021 Aug 4. doi: 10.1016/S2468-1253(21)00215-6.  

Dapagliflozin might reduce the risk for ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF), a post hoc analysis of the DAPA-HF trial suggests.

The addition of dapagliflozin to standard therapy reduced the relative risk for the primary composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%, compared with placebo (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99). The absolute risk reduction was 1.5% (5.9% vs. 7.4%).

The benefit was consistent in a competing-risks analysis that included all-cause mortality (HR, 0.80; P = .043) and across the individual components of the composite outcome, James Curtain, MD, Cardiovascular Research Centre of Glasgow, said at the annual congress of the European Society of Cardiology.

As previously reported from the main trial, treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor cut the primary endpoint of cardiovascular death or worsening heart failure by 26% among 4,744 patients with HFrEF and in New York Heart Association functional class 2-4.

Cochair of the late-breaking science session, Lars Lund, MD, Karolinska Institute, Stockholm, pointed out that dapagliflozin reduced sudden cardiac deaths and related events to an extent similar to that observed for cardiovascular deaths, total mortality, and the main trial’s primary endpoint.

“So does that mean it has any particular effect on arrhythmic events or does it mean, such as a beta-blocker, for example, [it] reduces calcium transience and improves handling of calcium, or does it have an effect simply by improving heart failure?” he asked.

Dr. Curtain replied they are still trying to understand the effects of this new class of drug but that studies have shown dapagliflozin and other SGLT2 inhibitors have favorable effects on adverse cardiac remodeling, which contributes to sudden death and ventricular arrhythmia. They’ve also been shown to reduce cardiac chamber size, left ventricular hypertrophy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over time, consistent with a reduction in myocardial wall stress. “So it could indeed be one of several mechanisms by which they may exert a beneficial cardiac effect.”

Speaking with this news organization, Dr. Curtain pointed out that the Kaplan-Meier curves for the composite outcome began to separate early on, but that the clearest separation was after 9 months, suggestive of a positive action on adverse cardiac remodeling over time.

“This would improve the patients’ heart failure situation, but also thick ventricles are a key risk factor for the occurrence of sudden death and ventricular arrhythmias,” he said. “The effects on adverse cardiac remodeling, given its plausibility in terms of our Kaplan-Meier curves, are one [mechanism] that I’d look to in the first instance, but I’m sure there are more than one actions at play.”

According to the new analysis, the primary outcome occurred in 315 (6.6%) patients; there were 203 adjudicated sudden deaths (64%), 104 investigator-reported ventricular arrhythmias (33%), and 8 resuscitated cardiac arrests (3%). Independent predictors of the primary outcome were higher NT-proBNP levels (odds ratio, 1.54), previous ventricular arrhythmia (OR, 1.93), previous myocardial infarction (OR, 1.42), male sex (OR, 1.53), and higher body mass index (OR, 1.03).

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

Dapagliflozin might reduce the risk for ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF), a post hoc analysis of the DAPA-HF trial suggests.

The addition of dapagliflozin to standard therapy reduced the relative risk for the primary composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%, compared with placebo (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99). The absolute risk reduction was 1.5% (5.9% vs. 7.4%).

The benefit was consistent in a competing-risks analysis that included all-cause mortality (HR, 0.80; P = .043) and across the individual components of the composite outcome, James Curtain, MD, Cardiovascular Research Centre of Glasgow, said at the annual congress of the European Society of Cardiology.

As previously reported from the main trial, treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor cut the primary endpoint of cardiovascular death or worsening heart failure by 26% among 4,744 patients with HFrEF and in New York Heart Association functional class 2-4.

Cochair of the late-breaking science session, Lars Lund, MD, Karolinska Institute, Stockholm, pointed out that dapagliflozin reduced sudden cardiac deaths and related events to an extent similar to that observed for cardiovascular deaths, total mortality, and the main trial’s primary endpoint.

“So does that mean it has any particular effect on arrhythmic events or does it mean, such as a beta-blocker, for example, [it] reduces calcium transience and improves handling of calcium, or does it have an effect simply by improving heart failure?” he asked.

Dr. Curtain replied they are still trying to understand the effects of this new class of drug but that studies have shown dapagliflozin and other SGLT2 inhibitors have favorable effects on adverse cardiac remodeling, which contributes to sudden death and ventricular arrhythmia. They’ve also been shown to reduce cardiac chamber size, left ventricular hypertrophy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over time, consistent with a reduction in myocardial wall stress. “So it could indeed be one of several mechanisms by which they may exert a beneficial cardiac effect.”

Speaking with this news organization, Dr. Curtain pointed out that the Kaplan-Meier curves for the composite outcome began to separate early on, but that the clearest separation was after 9 months, suggestive of a positive action on adverse cardiac remodeling over time.

“This would improve the patients’ heart failure situation, but also thick ventricles are a key risk factor for the occurrence of sudden death and ventricular arrhythmias,” he said. “The effects on adverse cardiac remodeling, given its plausibility in terms of our Kaplan-Meier curves, are one [mechanism] that I’d look to in the first instance, but I’m sure there are more than one actions at play.”

According to the new analysis, the primary outcome occurred in 315 (6.6%) patients; there were 203 adjudicated sudden deaths (64%), 104 investigator-reported ventricular arrhythmias (33%), and 8 resuscitated cardiac arrests (3%). Independent predictors of the primary outcome were higher NT-proBNP levels (odds ratio, 1.54), previous ventricular arrhythmia (OR, 1.93), previous myocardial infarction (OR, 1.42), male sex (OR, 1.53), and higher body mass index (OR, 1.03).

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

Dapagliflozin might reduce the risk for ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF), a post hoc analysis of the DAPA-HF trial suggests.

The addition of dapagliflozin to standard therapy reduced the relative risk for the primary composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%, compared with placebo (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99). The absolute risk reduction was 1.5% (5.9% vs. 7.4%).

The benefit was consistent in a competing-risks analysis that included all-cause mortality (HR, 0.80; P = .043) and across the individual components of the composite outcome, James Curtain, MD, Cardiovascular Research Centre of Glasgow, said at the annual congress of the European Society of Cardiology.

As previously reported from the main trial, treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor cut the primary endpoint of cardiovascular death or worsening heart failure by 26% among 4,744 patients with HFrEF and in New York Heart Association functional class 2-4.

Cochair of the late-breaking science session, Lars Lund, MD, Karolinska Institute, Stockholm, pointed out that dapagliflozin reduced sudden cardiac deaths and related events to an extent similar to that observed for cardiovascular deaths, total mortality, and the main trial’s primary endpoint.

“So does that mean it has any particular effect on arrhythmic events or does it mean, such as a beta-blocker, for example, [it] reduces calcium transience and improves handling of calcium, or does it have an effect simply by improving heart failure?” he asked.

Dr. Curtain replied they are still trying to understand the effects of this new class of drug but that studies have shown dapagliflozin and other SGLT2 inhibitors have favorable effects on adverse cardiac remodeling, which contributes to sudden death and ventricular arrhythmia. They’ve also been shown to reduce cardiac chamber size, left ventricular hypertrophy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over time, consistent with a reduction in myocardial wall stress. “So it could indeed be one of several mechanisms by which they may exert a beneficial cardiac effect.”

Speaking with this news organization, Dr. Curtain pointed out that the Kaplan-Meier curves for the composite outcome began to separate early on, but that the clearest separation was after 9 months, suggestive of a positive action on adverse cardiac remodeling over time.

“This would improve the patients’ heart failure situation, but also thick ventricles are a key risk factor for the occurrence of sudden death and ventricular arrhythmias,” he said. “The effects on adverse cardiac remodeling, given its plausibility in terms of our Kaplan-Meier curves, are one [mechanism] that I’d look to in the first instance, but I’m sure there are more than one actions at play.”

According to the new analysis, the primary outcome occurred in 315 (6.6%) patients; there were 203 adjudicated sudden deaths (64%), 104 investigator-reported ventricular arrhythmias (33%), and 8 resuscitated cardiac arrests (3%). Independent predictors of the primary outcome were higher NT-proBNP levels (odds ratio, 1.54), previous ventricular arrhythmia (OR, 1.93), previous myocardial infarction (OR, 1.42), male sex (OR, 1.53), and higher body mass index (OR, 1.03).

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

Artificial intelligence (AI)–powered neural networks modeled on real human brain connectivity patterns perform cognitive tasks better than traditional AI systems, new research suggests. “This work opens new opportunities to discover how the network organization of the brain optimizes cognitive capacity,” wrote researchers from The Neuro (Montreal Neurological Institute–Hospital) and the Quebec Artificial Intelligence Institute.

Courtesy Dr. Bratislav Misic

Senior investigator Bratislav Misic, PhD, said the research has potential clinical application for studying diseases of the brain, which is something his team is actively working on. “For example, using MRI techniques, we can measure different patterns of atrophy in neurodegenerative diseases such as Alzheimer’s disease,” he said.

“We can use these disease patterns from real patients to artificially lesion these connectomes and to ask how a particular disease causes a particular pattern of symptoms and cognitive deficits,” he added.

The findings were published online in Nature Machine Intelligence.

Unique approach

Using brain imaging data, the investigators reconstructed a human brain connectivity pattern and applied it to an artificial neural network. After training, the artificial neural network successfully performed a working memory task more flexibly and efficiently than other “benchmark” AI systems.

The researchers noted that their approach is unique because previous work on brain connectivity, also known as connectomics, has focused on describing brain organization without regard to how it actually functions.

Traditional artificial neural network have arbitrary structures that do not reflect how real brain networks are organized. Integrating brain connectomics into the construction of artificial neural network can reveal how the wiring of the brain supports specific cognitive skills, the investigators wrote.

“Up until now, if you look at how neural networks are constructed, the architectures that are used are very ad hoc and very problem specific,” Dr. Misic said. “But the connectomics revolution that’s happened in neuroscience over the past 20 years or so has given us the ability to really measure and trace out connection patterns in a variety of organisms, including the human brain.”

He noted that the researchers took wiring patterns of the real human brain and implemented it as an artificial neural network. They then “trained that network to perform a very simple cognitive task, and when you compare it to other benchmark architectures, it actually does better.”

This shows that there is “something fundamentally different about how the human brain is wired up and that the design principles that we can see in the human brain could be used to potentially build better artificial networks,” Dr. Misic concluded.

Funding for the research was provided by the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative, and by the Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Quebec – Santé, the Canadian Institute for Advanced Research, Canada Research Chairs, Fonds de Recherche du Quebec – Nature et Technologies, and the Centre UNIQUE (Union of Neuroscience and Artificial Intelligence). The investigators have reported no relevant financial relationships.

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

Artificial intelligence (AI)–powered neural networks modeled on real human brain connectivity patterns perform cognitive tasks better than traditional AI systems, new research suggests. “This work opens new opportunities to discover how the network organization of the brain optimizes cognitive capacity,” wrote researchers from The Neuro (Montreal Neurological Institute–Hospital) and the Quebec Artificial Intelligence Institute.

Courtesy Dr. Bratislav Misic

Senior investigator Bratislav Misic, PhD, said the research has potential clinical application for studying diseases of the brain, which is something his team is actively working on. “For example, using MRI techniques, we can measure different patterns of atrophy in neurodegenerative diseases such as Alzheimer’s disease,” he said.

“We can use these disease patterns from real patients to artificially lesion these connectomes and to ask how a particular disease causes a particular pattern of symptoms and cognitive deficits,” he added.

The findings were published online in Nature Machine Intelligence.

Unique approach

Using brain imaging data, the investigators reconstructed a human brain connectivity pattern and applied it to an artificial neural network. After training, the artificial neural network successfully performed a working memory task more flexibly and efficiently than other “benchmark” AI systems.

The researchers noted that their approach is unique because previous work on brain connectivity, also known as connectomics, has focused on describing brain organization without regard to how it actually functions.

Traditional artificial neural network have arbitrary structures that do not reflect how real brain networks are organized. Integrating brain connectomics into the construction of artificial neural network can reveal how the wiring of the brain supports specific cognitive skills, the investigators wrote.

“Up until now, if you look at how neural networks are constructed, the architectures that are used are very ad hoc and very problem specific,” Dr. Misic said. “But the connectomics revolution that’s happened in neuroscience over the past 20 years or so has given us the ability to really measure and trace out connection patterns in a variety of organisms, including the human brain.”

He noted that the researchers took wiring patterns of the real human brain and implemented it as an artificial neural network. They then “trained that network to perform a very simple cognitive task, and when you compare it to other benchmark architectures, it actually does better.”

This shows that there is “something fundamentally different about how the human brain is wired up and that the design principles that we can see in the human brain could be used to potentially build better artificial networks,” Dr. Misic concluded.

Funding for the research was provided by the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative, and by the Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Quebec – Santé, the Canadian Institute for Advanced Research, Canada Research Chairs, Fonds de Recherche du Quebec – Nature et Technologies, and the Centre UNIQUE (Union of Neuroscience and Artificial Intelligence). The investigators have reported no relevant financial relationships.

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

Artificial intelligence (AI)–powered neural networks modeled on real human brain connectivity patterns perform cognitive tasks better than traditional AI systems, new research suggests. “This work opens new opportunities to discover how the network organization of the brain optimizes cognitive capacity,” wrote researchers from The Neuro (Montreal Neurological Institute–Hospital) and the Quebec Artificial Intelligence Institute.

Courtesy Dr. Bratislav Misic

Senior investigator Bratislav Misic, PhD, said the research has potential clinical application for studying diseases of the brain, which is something his team is actively working on. “For example, using MRI techniques, we can measure different patterns of atrophy in neurodegenerative diseases such as Alzheimer’s disease,” he said.

“We can use these disease patterns from real patients to artificially lesion these connectomes and to ask how a particular disease causes a particular pattern of symptoms and cognitive deficits,” he added.

The findings were published online in Nature Machine Intelligence.

Unique approach

Using brain imaging data, the investigators reconstructed a human brain connectivity pattern and applied it to an artificial neural network. After training, the artificial neural network successfully performed a working memory task more flexibly and efficiently than other “benchmark” AI systems.

The researchers noted that their approach is unique because previous work on brain connectivity, also known as connectomics, has focused on describing brain organization without regard to how it actually functions.

Traditional artificial neural network have arbitrary structures that do not reflect how real brain networks are organized. Integrating brain connectomics into the construction of artificial neural network can reveal how the wiring of the brain supports specific cognitive skills, the investigators wrote.

“Up until now, if you look at how neural networks are constructed, the architectures that are used are very ad hoc and very problem specific,” Dr. Misic said. “But the connectomics revolution that’s happened in neuroscience over the past 20 years or so has given us the ability to really measure and trace out connection patterns in a variety of organisms, including the human brain.”

He noted that the researchers took wiring patterns of the real human brain and implemented it as an artificial neural network. They then “trained that network to perform a very simple cognitive task, and when you compare it to other benchmark architectures, it actually does better.”

This shows that there is “something fundamentally different about how the human brain is wired up and that the design principles that we can see in the human brain could be used to potentially build better artificial networks,” Dr. Misic concluded.

Funding for the research was provided by the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative, and by the Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Quebec – Santé, the Canadian Institute for Advanced Research, Canada Research Chairs, Fonds de Recherche du Quebec – Nature et Technologies, and the Centre UNIQUE (Union of Neuroscience and Artificial Intelligence). The investigators have reported no relevant financial relationships.

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

In the wake of the Centers for Disease Control and Prevention’s recommendation for a third COVID-19 mRNA vaccine dose for immunocompromised people and the Food and Drug Administration’s authorization of the third dose, the National Institute of Allergy and Infectious Diseases has begun a phase 2 trial to assess the antibody response to a booster dose of the Pfizer-BioNTech, Moderna, or Janssen vaccine in people with autoimmune disease who did not respond to their original COVID-19 vaccine regimen, according to an announcement.

The investigators of the trial, called COVID‐19 Booster Vaccine in Autoimmune Disease Non‐Responders, also want to determine if pausing immunosuppressive therapy for autoimmune disease improves the antibody response to an extra dose of a COVID-19 vaccine.

The trial will specifically look at the effects of mycophenolate mofetil (MMF) or mycophenolic acid (MPA), and methotrexate (MTX), or receipt of B cell–depletion therapy such as rituximab within the past 12 months on immune response to a booster dose in people with systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, or pemphigus. They have to have either no serologic response to their initial COVID-19 vaccine regimen or a suboptimal response, defined as a Roche Elecsys Anti-SARS-CoV-2 S (RBD) result greater than or equal to 50 U/mL.

The results of studies conducted in solid-organ transplant recipients who take immunosuppressants showed that an extra dose of vaccine could improve the immune response to the vaccine in many of the individuals, which suggests that the same approach might work in people with autoimmune disease who need treatment with immunosuppressive drugs. Improving the immune response of people with autoimmune disease to COVID-19 vaccines is important because higher rates of severe COVID-19 and death have been reported in this group of patients than in the general population, and it is unclear whether this is attributable to the autoimmune disease, the immunosuppressive medications taken to treat it, or both.

The open-label trial, conducted by the NIAID-funded Autoimmunity Centers of Excellence, aims to enroll 600 people aged 18 years and older with those conditions at 15-20 sites in the United States.

Because medications commonly taken by people with these conditions have been associated with poorer immune responses to vaccines, the trial will randomize the following two cohorts to stop or continue taking their immunosuppressive medication(s) or stop them before and after the booster according to protocol:

• Cohort 1 includes people who are taking MMF or MPA, without additional B cell–depleting medications or MTX.
• Cohort 2 includes people who are taking MTX without additional B cell–depleting medications or MMF/MPA.

A third, nonrandomized cohort consists of people who have received B cell–depletion therapy within the past 12 months regardless of whether they are also taking MMF/MPA or MTX.

Besides the cohort-specific exclusions, other rheumatic disease medications, including biologics, are allowed in the groups.

The primary outcome of the trial is the proportion of participants who have a protective antibody response at week 4. Secondary outcomes will examine various antibody responses at intervals, changes in disease activity across autoimmune diseases, adverse events, and SARS-CoV-2 infections out to 48 weeks.

Study participants will be followed for a total of 13 months. Preliminary results are expected in November 2021, according to the National Institutes of Health.

The trial is being led by Judith James, MD, PhD; Meggan Mackay, MD, MS; Dinesh Khanna, MBBS, MSc; and Amit Bar-Or, MD.

[email protected]

In the wake of the Centers for Disease Control and Prevention’s recommendation for a third COVID-19 mRNA vaccine dose for immunocompromised people and the Food and Drug Administration’s authorization of the third dose, the National Institute of Allergy and Infectious Diseases has begun a phase 2 trial to assess the antibody response to a booster dose of the Pfizer-BioNTech, Moderna, or Janssen vaccine in people with autoimmune disease who did not respond to their original COVID-19 vaccine regimen, according to an announcement.

The investigators of the trial, called COVID‐19 Booster Vaccine in Autoimmune Disease Non‐Responders, also want to determine if pausing immunosuppressive therapy for autoimmune disease improves the antibody response to an extra dose of a COVID-19 vaccine.

The trial will specifically look at the effects of mycophenolate mofetil (MMF) or mycophenolic acid (MPA), and methotrexate (MTX), or receipt of B cell–depletion therapy such as rituximab within the past 12 months on immune response to a booster dose in people with systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, or pemphigus. They have to have either no serologic response to their initial COVID-19 vaccine regimen or a suboptimal response, defined as a Roche Elecsys Anti-SARS-CoV-2 S (RBD) result greater than or equal to 50 U/mL.

The results of studies conducted in solid-organ transplant recipients who take immunosuppressants showed that an extra dose of vaccine could improve the immune response to the vaccine in many of the individuals, which suggests that the same approach might work in people with autoimmune disease who need treatment with immunosuppressive drugs. Improving the immune response of people with autoimmune disease to COVID-19 vaccines is important because higher rates of severe COVID-19 and death have been reported in this group of patients than in the general population, and it is unclear whether this is attributable to the autoimmune disease, the immunosuppressive medications taken to treat it, or both.

The open-label trial, conducted by the NIAID-funded Autoimmunity Centers of Excellence, aims to enroll 600 people aged 18 years and older with those conditions at 15-20 sites in the United States.

Because medications commonly taken by people with these conditions have been associated with poorer immune responses to vaccines, the trial will randomize the following two cohorts to stop or continue taking their immunosuppressive medication(s) or stop them before and after the booster according to protocol:

• Cohort 1 includes people who are taking MMF or MPA, without additional B cell–depleting medications or MTX.
• Cohort 2 includes people who are taking MTX without additional B cell–depleting medications or MMF/MPA.

A third, nonrandomized cohort consists of people who have received B cell–depletion therapy within the past 12 months regardless of whether they are also taking MMF/MPA or MTX.

Besides the cohort-specific exclusions, other rheumatic disease medications, including biologics, are allowed in the groups.

The primary outcome of the trial is the proportion of participants who have a protective antibody response at week 4. Secondary outcomes will examine various antibody responses at intervals, changes in disease activity across autoimmune diseases, adverse events, and SARS-CoV-2 infections out to 48 weeks.

Study participants will be followed for a total of 13 months. Preliminary results are expected in November 2021, according to the National Institutes of Health.

The trial is being led by Judith James, MD, PhD; Meggan Mackay, MD, MS; Dinesh Khanna, MBBS, MSc; and Amit Bar-Or, MD.

[email protected]

In the wake of the Centers for Disease Control and Prevention’s recommendation for a third COVID-19 mRNA vaccine dose for immunocompromised people and the Food and Drug Administration’s authorization of the third dose, the National Institute of Allergy and Infectious Diseases has begun a phase 2 trial to assess the antibody response to a booster dose of the Pfizer-BioNTech, Moderna, or Janssen vaccine in people with autoimmune disease who did not respond to their original COVID-19 vaccine regimen, according to an announcement.

The investigators of the trial, called COVID‐19 Booster Vaccine in Autoimmune Disease Non‐Responders, also want to determine if pausing immunosuppressive therapy for autoimmune disease improves the antibody response to an extra dose of a COVID-19 vaccine.

The trial will specifically look at the effects of mycophenolate mofetil (MMF) or mycophenolic acid (MPA), and methotrexate (MTX), or receipt of B cell–depletion therapy such as rituximab within the past 12 months on immune response to a booster dose in people with systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, or pemphigus. They have to have either no serologic response to their initial COVID-19 vaccine regimen or a suboptimal response, defined as a Roche Elecsys Anti-SARS-CoV-2 S (RBD) result greater than or equal to 50 U/mL.

The results of studies conducted in solid-organ transplant recipients who take immunosuppressants showed that an extra dose of vaccine could improve the immune response to the vaccine in many of the individuals, which suggests that the same approach might work in people with autoimmune disease who need treatment with immunosuppressive drugs. Improving the immune response of people with autoimmune disease to COVID-19 vaccines is important because higher rates of severe COVID-19 and death have been reported in this group of patients than in the general population, and it is unclear whether this is attributable to the autoimmune disease, the immunosuppressive medications taken to treat it, or both.

The open-label trial, conducted by the NIAID-funded Autoimmunity Centers of Excellence, aims to enroll 600 people aged 18 years and older with those conditions at 15-20 sites in the United States.

Because medications commonly taken by people with these conditions have been associated with poorer immune responses to vaccines, the trial will randomize the following two cohorts to stop or continue taking their immunosuppressive medication(s) or stop them before and after the booster according to protocol:

• Cohort 1 includes people who are taking MMF or MPA, without additional B cell–depleting medications or MTX.
• Cohort 2 includes people who are taking MTX without additional B cell–depleting medications or MMF/MPA.

A third, nonrandomized cohort consists of people who have received B cell–depletion therapy within the past 12 months regardless of whether they are also taking MMF/MPA or MTX.

Besides the cohort-specific exclusions, other rheumatic disease medications, including biologics, are allowed in the groups.

The primary outcome of the trial is the proportion of participants who have a protective antibody response at week 4. Secondary outcomes will examine various antibody responses at intervals, changes in disease activity across autoimmune diseases, adverse events, and SARS-CoV-2 infections out to 48 weeks.

Study participants will be followed for a total of 13 months. Preliminary results are expected in November 2021, according to the National Institutes of Health.

The trial is being led by Judith James, MD, PhD; Meggan Mackay, MD, MS; Dinesh Khanna, MBBS, MSc; and Amit Bar-Or, MD.

[email protected]