Key clinical point: Initial phase 2 results do not support combining pembrolizumab to neoadjuvant chemoradiotherapy after 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) treatment of locally advanced rectal cancer (LARC), despite being safe.

Major finding: The mean neoadjuvant rectal (NAR) score was not significantly different among patients treated with vsvs without pembrolizumab (difference, 2.55; P = .26). Grade 3/4 adverse events were slightly higher in patients receiving pembrolizumab vsvs those not (48.2% vsvs 37.3%).

Study details: Findings are from an open-label, phase 2 trial including 185 patients with stage II/III LARC at high risk for metastatic disease who were eligible for sphincter-sparing surgery. Patients were randomly assigned to receive FOLFOX (6 cycles) followed by chemoradiotherapy with (n=90) or without (n=95) intravenous pembrolizumab for up to 6 doses before surgery.

Disclosures: The study was supported by the National Cancer Institute and Merck. Some of the authors including the lead author reported receiving personal fees, grants, honoraria, and/or serving as a consultant and/or on advisory boards for various sources.

Source: Rahma OE et al. JAMA Oncol. 2021 Jul 1. doi: 10.1001/jamaoncol.2021.1683.

Key clinical point: Initial phase 2 results do not support combining pembrolizumab to neoadjuvant chemoradiotherapy after 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) treatment of locally advanced rectal cancer (LARC), despite being safe.

Major finding: The mean neoadjuvant rectal (NAR) score was not significantly different among patients treated with vsvs without pembrolizumab (difference, 2.55; P = .26). Grade 3/4 adverse events were slightly higher in patients receiving pembrolizumab vsvs those not (48.2% vsvs 37.3%).

Study details: Findings are from an open-label, phase 2 trial including 185 patients with stage II/III LARC at high risk for metastatic disease who were eligible for sphincter-sparing surgery. Patients were randomly assigned to receive FOLFOX (6 cycles) followed by chemoradiotherapy with (n=90) or without (n=95) intravenous pembrolizumab for up to 6 doses before surgery.

Disclosures: The study was supported by the National Cancer Institute and Merck. Some of the authors including the lead author reported receiving personal fees, grants, honoraria, and/or serving as a consultant and/or on advisory boards for various sources.

Source: Rahma OE et al. JAMA Oncol. 2021 Jul 1. doi: 10.1001/jamaoncol.2021.1683.

Key clinical point: Initial phase 2 results do not support combining pembrolizumab to neoadjuvant chemoradiotherapy after 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) treatment of locally advanced rectal cancer (LARC), despite being safe.

Major finding: The mean neoadjuvant rectal (NAR) score was not significantly different among patients treated with vsvs without pembrolizumab (difference, 2.55; P = .26). Grade 3/4 adverse events were slightly higher in patients receiving pembrolizumab vsvs those not (48.2% vsvs 37.3%).

Study details: Findings are from an open-label, phase 2 trial including 185 patients with stage II/III LARC at high risk for metastatic disease who were eligible for sphincter-sparing surgery. Patients were randomly assigned to receive FOLFOX (6 cycles) followed by chemoradiotherapy with (n=90) or without (n=95) intravenous pembrolizumab for up to 6 doses before surgery.

Disclosures: The study was supported by the National Cancer Institute and Merck. Some of the authors including the lead author reported receiving personal fees, grants, honoraria, and/or serving as a consultant and/or on advisory boards for various sources.

Source: Rahma OE et al. JAMA Oncol. 2021 Jul 1. doi: 10.1001/jamaoncol.2021.1683.

Key clinical point: Higher preoperative habitual dietary fiber intake was associated with a lower risk for postoperative complications among patients with colorectal cancer (CRC) who underwent surgery.

Major finding: Higher dietary fiber intake (per 10 grams/day) before surgery was significantly associated with a lower risk for any postoperative complications (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.62-0.92) and surgical postoperative complications (OR, 0.76; 95% CI, 0.60-0.97).

Study details: Findings are from a cohort study of 1,399 adult patients with stages I to IV CRC who underwent elective abdominal surgery.

Disclosures: The study was supported by grants from the Dutch Research Council. M van Zutphen and Dr. de Wilt reported receiving grants from various sources outside the submitted work.

Source: Kok DE et al. JAMA Surg. 2021 Jun 16. doi: 10.1001/jamasurg.2021.2311.

Key clinical point: Higher preoperative habitual dietary fiber intake was associated with a lower risk for postoperative complications among patients with colorectal cancer (CRC) who underwent surgery.

Major finding: Higher dietary fiber intake (per 10 grams/day) before surgery was significantly associated with a lower risk for any postoperative complications (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.62-0.92) and surgical postoperative complications (OR, 0.76; 95% CI, 0.60-0.97).

Study details: Findings are from a cohort study of 1,399 adult patients with stages I to IV CRC who underwent elective abdominal surgery.

Disclosures: The study was supported by grants from the Dutch Research Council. M van Zutphen and Dr. de Wilt reported receiving grants from various sources outside the submitted work.

Source: Kok DE et al. JAMA Surg. 2021 Jun 16. doi: 10.1001/jamasurg.2021.2311.

Key clinical point: Higher preoperative habitual dietary fiber intake was associated with a lower risk for postoperative complications among patients with colorectal cancer (CRC) who underwent surgery.

Major finding: Higher dietary fiber intake (per 10 grams/day) before surgery was significantly associated with a lower risk for any postoperative complications (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.62-0.92) and surgical postoperative complications (OR, 0.76; 95% CI, 0.60-0.97).

Study details: Findings are from a cohort study of 1,399 adult patients with stages I to IV CRC who underwent elective abdominal surgery.

Disclosures: The study was supported by grants from the Dutch Research Council. M van Zutphen and Dr. de Wilt reported receiving grants from various sources outside the submitted work.

Source: Kok DE et al. JAMA Surg. 2021 Jun 16. doi: 10.1001/jamasurg.2021.2311.

Key clinical point: Pituitrin 2 units (2U) for laparoscopic uterine myomectomy could provide a satisfactory surgical field with minimal hemodynamic changes.

Major finding: There were no differences among 2U, 4U, and 6U groups in the surgical condition quality. Pituitrin 2U significantly reduced blood loss vs pituitrin 0U, and increasing the pituitrin dose beyond 2U did not reduce blood loss further.

Study details: In a prospective, double-blind trial, 118 patients undergoing laparoscopic myomectomy were randomly assigned to receive 0U, 2U, 4U, or 6U of pituitrin injected into the myometrium surrounding the myoma.

Disclosures: The study was supported by grants from the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Guo F et al. J Minim Invasive Gynecol. 2021 Jun 17. doi: 10.1016/j.jmig.2021.06.008.

Key clinical point: Pituitrin 2 units (2U) for laparoscopic uterine myomectomy could provide a satisfactory surgical field with minimal hemodynamic changes.

Major finding: There were no differences among 2U, 4U, and 6U groups in the surgical condition quality. Pituitrin 2U significantly reduced blood loss vs pituitrin 0U, and increasing the pituitrin dose beyond 2U did not reduce blood loss further.

Study details: In a prospective, double-blind trial, 118 patients undergoing laparoscopic myomectomy were randomly assigned to receive 0U, 2U, 4U, or 6U of pituitrin injected into the myometrium surrounding the myoma.

Disclosures: The study was supported by grants from the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Guo F et al. J Minim Invasive Gynecol. 2021 Jun 17. doi: 10.1016/j.jmig.2021.06.008.

Key clinical point: Pituitrin 2 units (2U) for laparoscopic uterine myomectomy could provide a satisfactory surgical field with minimal hemodynamic changes.

Major finding: There were no differences among 2U, 4U, and 6U groups in the surgical condition quality. Pituitrin 2U significantly reduced blood loss vs pituitrin 0U, and increasing the pituitrin dose beyond 2U did not reduce blood loss further.

Study details: In a prospective, double-blind trial, 118 patients undergoing laparoscopic myomectomy were randomly assigned to receive 0U, 2U, 4U, or 6U of pituitrin injected into the myometrium surrounding the myoma.

Disclosures: The study was supported by grants from the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Guo F et al. J Minim Invasive Gynecol. 2021 Jun 17. doi: 10.1016/j.jmig.2021.06.008.

Key clinical point: Myomectomy is a cost-effective treatment option for uterine fibroids compared with uterine artery embolization (UAE).

Major finding: UAE was associated with higher mean costs (difference, £645; 95% confidence interval [CI], £−1,381 to £2,580) and lower quality-adjusted life years (difference, −0.09; 95% CI, −0.11 to −0.04) vs myomectomy over a 2-year follow-up period. Results were comparable over a 4-year follow-up period.

Study details: The data come from a cost-utility analysis of the FEMME trial. A total of 254 premenopausal women with symptomatic uterine fibroids were randomly assigned to either UAE (n=127) and myomectomy (n=127).

Disclosures: The study was supported by the National Institute of Health Research Health Technology Assessment programme. The authors declared no relevant conflicts of interest.

Source: Rana D et al. BJOG. 2021 May 30. doi: 10.1111/1471-0528.16781.

Key clinical point: Myomectomy is a cost-effective treatment option for uterine fibroids compared with uterine artery embolization (UAE).

Major finding: UAE was associated with higher mean costs (difference, £645; 95% confidence interval [CI], £−1,381 to £2,580) and lower quality-adjusted life years (difference, −0.09; 95% CI, −0.11 to −0.04) vs myomectomy over a 2-year follow-up period. Results were comparable over a 4-year follow-up period.

Study details: The data come from a cost-utility analysis of the FEMME trial. A total of 254 premenopausal women with symptomatic uterine fibroids were randomly assigned to either UAE (n=127) and myomectomy (n=127).

Disclosures: The study was supported by the National Institute of Health Research Health Technology Assessment programme. The authors declared no relevant conflicts of interest.

Source: Rana D et al. BJOG. 2021 May 30. doi: 10.1111/1471-0528.16781.

Key clinical point: Myomectomy is a cost-effective treatment option for uterine fibroids compared with uterine artery embolization (UAE).

Major finding: UAE was associated with higher mean costs (difference, £645; 95% confidence interval [CI], £−1,381 to £2,580) and lower quality-adjusted life years (difference, −0.09; 95% CI, −0.11 to −0.04) vs myomectomy over a 2-year follow-up period. Results were comparable over a 4-year follow-up period.

Study details: The data come from a cost-utility analysis of the FEMME trial. A total of 254 premenopausal women with symptomatic uterine fibroids were randomly assigned to either UAE (n=127) and myomectomy (n=127).

Disclosures: The study was supported by the National Institute of Health Research Health Technology Assessment programme. The authors declared no relevant conflicts of interest.

Source: Rana D et al. BJOG. 2021 May 30. doi: 10.1111/1471-0528.16781.

Key clinical point: Seroprevalence of herpes simplex virus (HSV)-2 was not associated with incidence and growth of ultrasound-diagnosed uterine fibroids in young African-American women.

Major finding: HSV-2 seropositivity had no significant association with fibroid incidence (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.69-1.12) or growth 3.1% (95% CI, −5.8% to 13.0%).

Study details: A cohort study examined the associations of HSV-2 with fibroid incidence and growth among African-American women aged 23-35 years who underwent ultrasound fibroid screening.

Disclosures: This study was supported by the Intramural Research Program of the National Institute of Health, the National Institute of Environmental Health Sciences, and the American Recovery and Reinvestment Act funds designated for the National Institute of Health Research. The authors declared no conflicts of interest.

Source: Moore KR et al. Am J Epidemiol. 2021 May 27. doi: 10.1093/aje/kwab160.

Key clinical point: Seroprevalence of herpes simplex virus (HSV)-2 was not associated with incidence and growth of ultrasound-diagnosed uterine fibroids in young African-American women.

Major finding: HSV-2 seropositivity had no significant association with fibroid incidence (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.69-1.12) or growth 3.1% (95% CI, −5.8% to 13.0%).

Study details: A cohort study examined the associations of HSV-2 with fibroid incidence and growth among African-American women aged 23-35 years who underwent ultrasound fibroid screening.

Disclosures: This study was supported by the Intramural Research Program of the National Institute of Health, the National Institute of Environmental Health Sciences, and the American Recovery and Reinvestment Act funds designated for the National Institute of Health Research. The authors declared no conflicts of interest.

Source: Moore KR et al. Am J Epidemiol. 2021 May 27. doi: 10.1093/aje/kwab160.

Key clinical point: Seroprevalence of herpes simplex virus (HSV)-2 was not associated with incidence and growth of ultrasound-diagnosed uterine fibroids in young African-American women.

Major finding: HSV-2 seropositivity had no significant association with fibroid incidence (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.69-1.12) or growth 3.1% (95% CI, −5.8% to 13.0%).

Study details: A cohort study examined the associations of HSV-2 with fibroid incidence and growth among African-American women aged 23-35 years who underwent ultrasound fibroid screening.

Disclosures: This study was supported by the Intramural Research Program of the National Institute of Health, the National Institute of Environmental Health Sciences, and the American Recovery and Reinvestment Act funds designated for the National Institute of Health Research. The authors declared no conflicts of interest.

Source: Moore KR et al. Am J Epidemiol. 2021 May 27. doi: 10.1093/aje/kwab160.

Key clinical point: A fifth of clinically stable patients receiving intermittent ulipristal acetate (UPA) treatment for uterine fibroids needed surgery after it was suspended by the European Medicines Agency in March 2020, because of safety concerns.

Major finding: Following the suspension of UPA, 20% of patients receiving intermittent UPA needed surgery and 80% needed other medical treatments.

Study details: The data come from an analysis of 85 women who received intermittent UPA treatment until it was suspended in March 2020.

Disclosures: No funding information was available. The authors declared no conflicts of interest.

Source: Nicolás I et al. Gynecol Endocrinol. 2021 May 28. doi: 10.1080/09513590.2021.1929152.

Key clinical point: A fifth of clinically stable patients receiving intermittent ulipristal acetate (UPA) treatment for uterine fibroids needed surgery after it was suspended by the European Medicines Agency in March 2020, because of safety concerns.

Major finding: Following the suspension of UPA, 20% of patients receiving intermittent UPA needed surgery and 80% needed other medical treatments.

Study details: The data come from an analysis of 85 women who received intermittent UPA treatment until it was suspended in March 2020.

Disclosures: No funding information was available. The authors declared no conflicts of interest.

Source: Nicolás I et al. Gynecol Endocrinol. 2021 May 28. doi: 10.1080/09513590.2021.1929152.

Key clinical point: A fifth of clinically stable patients receiving intermittent ulipristal acetate (UPA) treatment for uterine fibroids needed surgery after it was suspended by the European Medicines Agency in March 2020, because of safety concerns.

Major finding: Following the suspension of UPA, 20% of patients receiving intermittent UPA needed surgery and 80% needed other medical treatments.

Study details: The data come from an analysis of 85 women who received intermittent UPA treatment until it was suspended in March 2020.

Disclosures: No funding information was available. The authors declared no conflicts of interest.

Source: Nicolás I et al. Gynecol Endocrinol. 2021 May 28. doi: 10.1080/09513590.2021.1929152.

Key clinical point: Application of temporary uterine tourniquet may be effective in reducing perioperative bleeding in patients with multiple, large-sized uterine fibroids in close proximity of vascular structures.

Major finding: The tourniquet applied group vs not applied group had more favorable outcomes in terms of hemoglobin drop (P = .019), hematocrit drop (P = .023), transfusion amount (P = .012), operation time (P = .044), and duration of hospitalization (P = .036).

Study details: The data come from a retrospective study involving 84 patients who underwent abdominal myomectomy and were categorized into 2 groups according to the use (n=36) or nonuse (n=48) of a temporary uterine tourniquet.

Disclosures: The study did not receive any financial support. The authors declared no conflicts of interest.

Source: Akbaba E et al. J Turk Ger Gynecol Assoc. 2021 Jun 8. doi: 10.4274/jtgga.galenos.2021.2020.0242.

Key clinical point: Application of temporary uterine tourniquet may be effective in reducing perioperative bleeding in patients with multiple, large-sized uterine fibroids in close proximity of vascular structures.

Major finding: The tourniquet applied group vs not applied group had more favorable outcomes in terms of hemoglobin drop (P = .019), hematocrit drop (P = .023), transfusion amount (P = .012), operation time (P = .044), and duration of hospitalization (P = .036).

Study details: The data come from a retrospective study involving 84 patients who underwent abdominal myomectomy and were categorized into 2 groups according to the use (n=36) or nonuse (n=48) of a temporary uterine tourniquet.

Disclosures: The study did not receive any financial support. The authors declared no conflicts of interest.

Source: Akbaba E et al. J Turk Ger Gynecol Assoc. 2021 Jun 8. doi: 10.4274/jtgga.galenos.2021.2020.0242.

Key clinical point: Application of temporary uterine tourniquet may be effective in reducing perioperative bleeding in patients with multiple, large-sized uterine fibroids in close proximity of vascular structures.

Major finding: The tourniquet applied group vs not applied group had more favorable outcomes in terms of hemoglobin drop (P = .019), hematocrit drop (P = .023), transfusion amount (P = .012), operation time (P = .044), and duration of hospitalization (P = .036).

Study details: The data come from a retrospective study involving 84 patients who underwent abdominal myomectomy and were categorized into 2 groups according to the use (n=36) or nonuse (n=48) of a temporary uterine tourniquet.

Disclosures: The study did not receive any financial support. The authors declared no conflicts of interest.

Source: Akbaba E et al. J Turk Ger Gynecol Assoc. 2021 Jun 8. doi: 10.4274/jtgga.galenos.2021.2020.0242.

Key clinical point: Ultrasound-guided microwave ablation (MWA) is a safe and effective minimally invasive treatment strategy for symptomatic uterine fibroids.

Major finding: In patients treated with MWA, uterine fibroid symptom scores decreased significantly (reduction rate, 65.9%; P less than .0001) and the quality of life scores (increasing rate, 72.0%; P less than .0001) and hemoglobin levels increased significantly (increasing rate, 30.3%; P less than .0001) from baseline to follow-up. No major adverse events were reported.

Study details: A meta-analysis of 10 studies involving 671 patients.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Liu L et al. J Minim Invasive Gynecol. 2021 Jun 28. doi: 10.1016/j.jmig.2021.06.020.

Key clinical point: Ultrasound-guided microwave ablation (MWA) is a safe and effective minimally invasive treatment strategy for symptomatic uterine fibroids.

Major finding: In patients treated with MWA, uterine fibroid symptom scores decreased significantly (reduction rate, 65.9%; P less than .0001) and the quality of life scores (increasing rate, 72.0%; P less than .0001) and hemoglobin levels increased significantly (increasing rate, 30.3%; P less than .0001) from baseline to follow-up. No major adverse events were reported.

Study details: A meta-analysis of 10 studies involving 671 patients.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Liu L et al. J Minim Invasive Gynecol. 2021 Jun 28. doi: 10.1016/j.jmig.2021.06.020.

Key clinical point: Ultrasound-guided microwave ablation (MWA) is a safe and effective minimally invasive treatment strategy for symptomatic uterine fibroids.

Major finding: In patients treated with MWA, uterine fibroid symptom scores decreased significantly (reduction rate, 65.9%; P less than .0001) and the quality of life scores (increasing rate, 72.0%; P less than .0001) and hemoglobin levels increased significantly (increasing rate, 30.3%; P less than .0001) from baseline to follow-up. No major adverse events were reported.

Study details: A meta-analysis of 10 studies involving 671 patients.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Liu L et al. J Minim Invasive Gynecol. 2021 Jun 28. doi: 10.1016/j.jmig.2021.06.020.

Plasma biomarkers such as amyloid-beta 40 and 42, phosphorylated tau 181 and 217, and neurofilament light hold great promise for diagnosing and determining a prognosis for Alzheimer’s disease. Such tests are likely to be widely available in the near future.

But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.

“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
 

Case in point

To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.

After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.

The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.

Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.

“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
 

Other considerations

Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.

These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.

But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.

Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.

Plasma biomarkers such as amyloid-beta 40 and 42, phosphorylated tau 181 and 217, and neurofilament light hold great promise for diagnosing and determining a prognosis for Alzheimer’s disease. Such tests are likely to be widely available in the near future.

But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.

“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
 

Case in point

To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.

After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.

The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.

Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.

“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
 

Other considerations

Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.

These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.

But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.

Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.

Plasma biomarkers such as amyloid-beta 40 and 42, phosphorylated tau 181 and 217, and neurofilament light hold great promise for diagnosing and determining a prognosis for Alzheimer’s disease. Such tests are likely to be widely available in the near future.

But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.

“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
 

Case in point

To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.

After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.

The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.

Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.

“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
 

Other considerations

Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.

These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.

But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.

Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.

A Tennessee woman is suing a family physician and physician assistant (PA) after her husband’s death from COVID-19, claiming the health providers failed to properly test the man and rendered improper care that led to his demise.

Shirley Dimoh of Memphis alleges her husband Peter Dimoh, 66, received inadequate care when he presented with COVID-19 symptoms to May Medical Group in Munford, Tenn., on November 19, 2020. Physician assistant Robert Moody ordered a COVID-19 blood test for Mr. Dimoh, rather than a nasal swab test, which was sent to an Atlanta lab for analysis, according to the lawsuit.

By the time the Dimohs were informed of the positive result on November 23, Mr. Dimoh was seriously ill and showed signs of severe infection, the claim alleges. Family physician David Krapf, DO, then prescribed methocarbamol, a muscle relaxant, which the complaint claims exacerbated Mr. Dimoh’s infection, caused serious adverse reactions, and led to his death on December 16, 2020.

“Mr. Dimoh had multiple comorbid conditions and he had a positive test, he should have been referred to a specialist at a higher level of care,” said Duncan E. Ragsdale, a Memphis-based attorney representing Shirley Dimoh. “This is not something for a family physician or a physician assistant to be attempting to handle. It’s my belief this was a preventable death.”

Shirley Dimoh filed a lawsuit against May Medical Group, Moody, Krapf, and several others on June 23, 2021, in the Circuit Court of Tennessee, 13th Judicial District. She accuses the group of negligence, failure to refer, and failure to supervise, among other claims. She is requesting $5 million in damages.

May Medical Group did not return phone or email messages seeking comment for this story. The group had not issued a reply to the lawsuit as of this article’s deadline. An attorney for the practice is not yet listed in court records.
 

Wife had COVID-19 first, treated by same PA

Shirley Dimoh was the first of the couple to contract COVID-19. She visited May Medical Group with COVID-19 symptoms on November 9, according to the lawsuit. The same physician assistant allegedly prescribed antibiotics and sent Shirley Dimoh to the health department for a rapid nasal swab test. After a positive test resulted, she was prescribed more antibiotics, steroids, and other medications, according to the claim. She recovered without complications.

The plaintiff alleges the medical practice did not warn Peter Dimoh of the risk of contracting COVID-19 from contact with Shirley Dimoh or offer prophylactics against infection. Peter Dimoh had underlying conditions that included diabetes and kidney failure, according to Mr. Ragsdale.

It’s unclear why Peter Dimoh may have been prescribed methocarbamol after his positive COVID-19 test on November 23. The same day, Shirley Dimoh went to the pharmacy to pick up her husband’s prescription because he was too sick to go himself, the complaint states. Mr. Dimoh took the medication three times a day as prescribed. The methocarbamol was “unreasonably dangerous” for Mr. Dimoh at the time and caused an injury he would have not incurred otherwise, the suit claims.

On November 28, Mr. Dimoh collapsed and was taken by ambulance to Methodist Hospital in Memphis. He was treated for COVID-19 as well as bacterial pneumonia, severe sepsis, and sytemic inflammatory response syndrome, according to the complaint. He died December 16 from respiratory and heart failure.

“What’s interesting about this case is that you’ve got a good example and a bad example together,” Mr. Ragsdale said. “In other words, the good example is they treated her appropriately, she recovered. They didn’t treat him at all, he died. I don’t know how you could have a better counter position established by the same practice.”
 

Family has sued for malpractice before

Before his death, Peter Dimoh was the plaintiff in another medical negligence suit. In 2013, he sued the Center for Oral and Facial Surgery of Memphis and two oral surgeons for allegedly operating on him improperly and causing an adverse outcome.  

Mr. Dimoh underwent oral surgery on February 8, 2012, at the center. The day of his operation, Mr. Dimoh’s A1c and glucose levels were grossly elevated, according to the claim, which was also represented by Mr. Ragsdale. Surgeons concluded, incorrectly, that Mr. Dimoh’s diabetes was under control, the complaint alleges, failed to order preoperative antibiotics, operated on him, and caused a bacterial infection at the operative site. The infection allegedly resulted in osteomyelitis of Mr. Dimoh’s left mandible with a pathologic fracture.

The complaint also alleges that although Mr. Dimoh signed a consent form for the surgery, the defendants failed to obtain his consent because they were unaware his diabetes was not under control and they did not explain the risks of surgery while in such a condition. The suit alleges lack of informed consent, negligence, and gross negligence by the practice and requests $2 million in damages. 

Court documents show the suit was voluntarily withdrawn in 2018 without prejudice and reissued in 2019. In January 2021, the court was given notice of Mr. Dimoh’s death, and a motion was made to substitute another plaintiff, according to Shelby County court records.

An attorney for the Center for Oral and Facial Surgery of Memphis did not return a message seeking comment.

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

A Tennessee woman is suing a family physician and physician assistant (PA) after her husband’s death from COVID-19, claiming the health providers failed to properly test the man and rendered improper care that led to his demise.

Shirley Dimoh of Memphis alleges her husband Peter Dimoh, 66, received inadequate care when he presented with COVID-19 symptoms to May Medical Group in Munford, Tenn., on November 19, 2020. Physician assistant Robert Moody ordered a COVID-19 blood test for Mr. Dimoh, rather than a nasal swab test, which was sent to an Atlanta lab for analysis, according to the lawsuit.

By the time the Dimohs were informed of the positive result on November 23, Mr. Dimoh was seriously ill and showed signs of severe infection, the claim alleges. Family physician David Krapf, DO, then prescribed methocarbamol, a muscle relaxant, which the complaint claims exacerbated Mr. Dimoh’s infection, caused serious adverse reactions, and led to his death on December 16, 2020.

“Mr. Dimoh had multiple comorbid conditions and he had a positive test, he should have been referred to a specialist at a higher level of care,” said Duncan E. Ragsdale, a Memphis-based attorney representing Shirley Dimoh. “This is not something for a family physician or a physician assistant to be attempting to handle. It’s my belief this was a preventable death.”

Shirley Dimoh filed a lawsuit against May Medical Group, Moody, Krapf, and several others on June 23, 2021, in the Circuit Court of Tennessee, 13th Judicial District. She accuses the group of negligence, failure to refer, and failure to supervise, among other claims. She is requesting $5 million in damages.

May Medical Group did not return phone or email messages seeking comment for this story. The group had not issued a reply to the lawsuit as of this article’s deadline. An attorney for the practice is not yet listed in court records.
 

Wife had COVID-19 first, treated by same PA

Shirley Dimoh was the first of the couple to contract COVID-19. She visited May Medical Group with COVID-19 symptoms on November 9, according to the lawsuit. The same physician assistant allegedly prescribed antibiotics and sent Shirley Dimoh to the health department for a rapid nasal swab test. After a positive test resulted, she was prescribed more antibiotics, steroids, and other medications, according to the claim. She recovered without complications.

The plaintiff alleges the medical practice did not warn Peter Dimoh of the risk of contracting COVID-19 from contact with Shirley Dimoh or offer prophylactics against infection. Peter Dimoh had underlying conditions that included diabetes and kidney failure, according to Mr. Ragsdale.

It’s unclear why Peter Dimoh may have been prescribed methocarbamol after his positive COVID-19 test on November 23. The same day, Shirley Dimoh went to the pharmacy to pick up her husband’s prescription because he was too sick to go himself, the complaint states. Mr. Dimoh took the medication three times a day as prescribed. The methocarbamol was “unreasonably dangerous” for Mr. Dimoh at the time and caused an injury he would have not incurred otherwise, the suit claims.

On November 28, Mr. Dimoh collapsed and was taken by ambulance to Methodist Hospital in Memphis. He was treated for COVID-19 as well as bacterial pneumonia, severe sepsis, and sytemic inflammatory response syndrome, according to the complaint. He died December 16 from respiratory and heart failure.

“What’s interesting about this case is that you’ve got a good example and a bad example together,” Mr. Ragsdale said. “In other words, the good example is they treated her appropriately, she recovered. They didn’t treat him at all, he died. I don’t know how you could have a better counter position established by the same practice.”
 

Family has sued for malpractice before

Before his death, Peter Dimoh was the plaintiff in another medical negligence suit. In 2013, he sued the Center for Oral and Facial Surgery of Memphis and two oral surgeons for allegedly operating on him improperly and causing an adverse outcome.  

Mr. Dimoh underwent oral surgery on February 8, 2012, at the center. The day of his operation, Mr. Dimoh’s A1c and glucose levels were grossly elevated, according to the claim, which was also represented by Mr. Ragsdale. Surgeons concluded, incorrectly, that Mr. Dimoh’s diabetes was under control, the complaint alleges, failed to order preoperative antibiotics, operated on him, and caused a bacterial infection at the operative site. The infection allegedly resulted in osteomyelitis of Mr. Dimoh’s left mandible with a pathologic fracture.

The complaint also alleges that although Mr. Dimoh signed a consent form for the surgery, the defendants failed to obtain his consent because they were unaware his diabetes was not under control and they did not explain the risks of surgery while in such a condition. The suit alleges lack of informed consent, negligence, and gross negligence by the practice and requests $2 million in damages. 

Court documents show the suit was voluntarily withdrawn in 2018 without prejudice and reissued in 2019. In January 2021, the court was given notice of Mr. Dimoh’s death, and a motion was made to substitute another plaintiff, according to Shelby County court records.

An attorney for the Center for Oral and Facial Surgery of Memphis did not return a message seeking comment.

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

A Tennessee woman is suing a family physician and physician assistant (PA) after her husband’s death from COVID-19, claiming the health providers failed to properly test the man and rendered improper care that led to his demise.

Shirley Dimoh of Memphis alleges her husband Peter Dimoh, 66, received inadequate care when he presented with COVID-19 symptoms to May Medical Group in Munford, Tenn., on November 19, 2020. Physician assistant Robert Moody ordered a COVID-19 blood test for Mr. Dimoh, rather than a nasal swab test, which was sent to an Atlanta lab for analysis, according to the lawsuit.

By the time the Dimohs were informed of the positive result on November 23, Mr. Dimoh was seriously ill and showed signs of severe infection, the claim alleges. Family physician David Krapf, DO, then prescribed methocarbamol, a muscle relaxant, which the complaint claims exacerbated Mr. Dimoh’s infection, caused serious adverse reactions, and led to his death on December 16, 2020.

“Mr. Dimoh had multiple comorbid conditions and he had a positive test, he should have been referred to a specialist at a higher level of care,” said Duncan E. Ragsdale, a Memphis-based attorney representing Shirley Dimoh. “This is not something for a family physician or a physician assistant to be attempting to handle. It’s my belief this was a preventable death.”

Shirley Dimoh filed a lawsuit against May Medical Group, Moody, Krapf, and several others on June 23, 2021, in the Circuit Court of Tennessee, 13th Judicial District. She accuses the group of negligence, failure to refer, and failure to supervise, among other claims. She is requesting $5 million in damages.

May Medical Group did not return phone or email messages seeking comment for this story. The group had not issued a reply to the lawsuit as of this article’s deadline. An attorney for the practice is not yet listed in court records.
 

Wife had COVID-19 first, treated by same PA

Shirley Dimoh was the first of the couple to contract COVID-19. She visited May Medical Group with COVID-19 symptoms on November 9, according to the lawsuit. The same physician assistant allegedly prescribed antibiotics and sent Shirley Dimoh to the health department for a rapid nasal swab test. After a positive test resulted, she was prescribed more antibiotics, steroids, and other medications, according to the claim. She recovered without complications.

The plaintiff alleges the medical practice did not warn Peter Dimoh of the risk of contracting COVID-19 from contact with Shirley Dimoh or offer prophylactics against infection. Peter Dimoh had underlying conditions that included diabetes and kidney failure, according to Mr. Ragsdale.

It’s unclear why Peter Dimoh may have been prescribed methocarbamol after his positive COVID-19 test on November 23. The same day, Shirley Dimoh went to the pharmacy to pick up her husband’s prescription because he was too sick to go himself, the complaint states. Mr. Dimoh took the medication three times a day as prescribed. The methocarbamol was “unreasonably dangerous” for Mr. Dimoh at the time and caused an injury he would have not incurred otherwise, the suit claims.

On November 28, Mr. Dimoh collapsed and was taken by ambulance to Methodist Hospital in Memphis. He was treated for COVID-19 as well as bacterial pneumonia, severe sepsis, and sytemic inflammatory response syndrome, according to the complaint. He died December 16 from respiratory and heart failure.

“What’s interesting about this case is that you’ve got a good example and a bad example together,” Mr. Ragsdale said. “In other words, the good example is they treated her appropriately, she recovered. They didn’t treat him at all, he died. I don’t know how you could have a better counter position established by the same practice.”
 

Family has sued for malpractice before

Before his death, Peter Dimoh was the plaintiff in another medical negligence suit. In 2013, he sued the Center for Oral and Facial Surgery of Memphis and two oral surgeons for allegedly operating on him improperly and causing an adverse outcome.  

Mr. Dimoh underwent oral surgery on February 8, 2012, at the center. The day of his operation, Mr. Dimoh’s A1c and glucose levels were grossly elevated, according to the claim, which was also represented by Mr. Ragsdale. Surgeons concluded, incorrectly, that Mr. Dimoh’s diabetes was under control, the complaint alleges, failed to order preoperative antibiotics, operated on him, and caused a bacterial infection at the operative site. The infection allegedly resulted in osteomyelitis of Mr. Dimoh’s left mandible with a pathologic fracture.

The complaint also alleges that although Mr. Dimoh signed a consent form for the surgery, the defendants failed to obtain his consent because they were unaware his diabetes was not under control and they did not explain the risks of surgery while in such a condition. The suit alleges lack of informed consent, negligence, and gross negligence by the practice and requests $2 million in damages. 

Court documents show the suit was voluntarily withdrawn in 2018 without prejudice and reissued in 2019. In January 2021, the court was given notice of Mr. Dimoh’s death, and a motion was made to substitute another plaintiff, according to Shelby County court records.

An attorney for the Center for Oral and Facial Surgery of Memphis did not return a message seeking comment.

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