Citations

Background: We have previously reported that carotid artery stenting (CAS) carries a higher stroke risk than carotid endarterectomy (CEA) in patients over the age of 70. The question arises if advanced age is a surrogate for other factors? If so, can those factors be separately identified such that advanced chronological age alone would not be considered a contra-indication for CAS? Here we consider whether the CAS/CEA choice could be guided by other factors known in the clinical center at the time of patient evaluation, independent of age, in order to provide optimal 4-year outcomes. Methods: Demographic factors (age, sex and race), symptomatic status, patient risk factors (hypertension, diabetes, dyslipidemia, smoking), and arterial characteristics (percent stenosis) were available on 2,502 patients. Additional detailed arterial characteristics (ulcerated plaque, distal tortuosity, sequential lesions, circumferential calcification) were available on 1141 CAS and 438 CEA patients. Potential differential treatment efficacy was assessed by the addition of factor-by-treatment interaction terms to a proportional hazard model containing established predictors of outcome (treatment, symptomatic status, sex, age and age-by-treatment interaction). Results: No other factor was found to mitigate advanced age with evidence of additional treatment effect modification of 4-year outcome (p > 0.10). Discussion: Beyond the previously described differential treatment efficacy by age, there were no other patient or arterial characteristic detected to identify patient subgroups that would differentially benefit from the choice of CAS versus CEA. Our inability to identify factors to guide treatment choices could be due to the low number of stroke and death events, incomplete information regarding arterial characteristics in the CEA population, or the potential exclusion of “high risk” groups (such as those with severe arterial tortuosity) from the study.

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) enrolled 2502 patients between December of 2000 and mid-July of 2008. We analyzed temporal changes in outcomes for both CEA and CAS over the course of this study. Methods Enrollment was divided into 3 consecutive epochs (5 years, 14 months, and 16 months), each with approximately 834 patients ( Table ). Rates for the primary outcome of death, stroke, and myocardial infarction (DSMI) and for death and stroke (DS) during the periprocedural period were calculated. Poisson regression was used to adjust rates for age, sex, dyslipidemia, and symptomatic status, all of which were found to influence outcomes. Results For CAS, there was a 26% decline in DSMI (6.2% → 4.6%) and a 35% decline in DS (5.5% → 3.6%). For both composite endpoints in CEA there was no consistent pattern ( Table ). As CREST progressed, it enrolled younger patients, more men, patients more likely to be dyslipidemic and enrolled more asymptomatic patients (all p < 0.05). Adjustment for these changes mediated the improvement in event rates for the CAS patients, and had no consistent effect on CEA event rates ( Table ). Conclusion Periprocedural safety for CAS improved over time in CREST. Changes were inconsistent for CEA. Improvements for CAS in part appear to reflect changes in patient selection related to age, sex, and risk factors, as adjustment for those variables attenuated the decline in rates. Linking rates to operator experience was not feasible because of the large number of new interventionalists and surgeons entering CREST over time.

Introduction: Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease (ASCVD), yet little is known about Lp(a) testing patterns in real-world practice. We hypothesized that Lp(a) testing occurs in a different population than calculated low density lipoprotein (LDL-C) testing alone, and that elevated Lp(a) is associated with greater lipid-lowering therapy (LLT) initiation and cardiovascular (CV) events. Methods: We used data from 11 health systems participating in the National Patient-Centered Clinical Research Network. We created two cohorts based on lab tests from Jan 1, 2015 to Dec 31, 2019: 1) the Lp(a) cohort, of adults with an Lp(a) test and 2) the LDL-C cohort, of 4:1 date- and site-matched adults with an LDL-C test, but no Lp(a) test. We used logistic regression to assess the relationship between Lp(a) levels (< 50, 50-100, and > 100mg/dL) and initiation of LLT within 3 months; and cox proportional hazards to evaluate Lp(a) levels and time to all-cause hospitalization and the composite of MI, revascularization and ischemic stroke hospitalization. Results: Overall, 20,551 patients (0.06% per year) had Lp(a) tests, with median Lp(a) value 17.5mg/dL (Q1, Q3: 7.0, 56.0). Compared with the LDL-C cohort (N=82,204), the Lp(a) cohort more frequently had ASCVD (24.3% vs. 8.5%) or multiple prior CV events (8.6% vs. 2.6%). Elevated Lp(a) was associated with greater odds of LLT initiation (Figure 1). Elevated Lp(a) was not significantly associated with all-cause hospitalization; however, Lp(a) > 100mg/dL was correlated with composite CV hospitalization compared with Lp(a) < 50mg/dL [adj HR (95% CI): 1.24 (1.06-1.44), p=0.006]. Conclusions: Lp(a) testing occurs more often in adults with ASCVD and multiple CV events, but testing is infrequent. Elevated Lp(a) was associated with LLT initiation, including niacin, despite lack of evidence of CV benefit. There was an association between elevated Lp(a) and CV hospitalization outcomes.

Background: Women and African Americans with atrial fibrillation (AF) experience higher rates of stroke compared to men and white AF patients, respectively. However, sex and race differences for cardiovascular outcomes other than stroke have not been specifically evaluated in patients with AF. Methods: We studied patients with AF in the Optum Clinformatics database between 2009 and 2015 with at least 6 months of enrollment before AF diagnosis. The Optum Clinformatics database includes medical and pharmacy claims and sociodemographic information on privately insured and Medicare Advantage enrollees throughout the US. Endpoints (hospitalizations for ischemic stroke, heart failure (HF), myocardial infarction (MI)) and covariates were defined using validated algorithms. Multivariable Cox models were used to study the association of race and sex with endpoints of interest. Results: The analysis included 380,636 eligible participants (mean age 73, women 45%). Of them, 82% were white, 9% African American, 7% Hispanic and 2% Asian American. During a mean follow-up of 23 months, 7,235 suffered ischemic stroke, 17,258 HF, and 5,585 MI. Crude rates of ischemic stroke and HF were higher in women than men, while men had higher rates of MI than women (Table). African Americans and Hispanics had higher rates of all studied outcomes than whites and Asian Americans. In models including age, sex, race, education and CHA 2 DS 2 -VASc score, women had higher risk of ischemic stroke and lower risk of HF and MI compared to men. Compared to whites, African Americans had 1.4 times the rate of HF and stroke, and 1.1 times the rate of MI, while Asian Americans had 16% lower rates of HF. No major differences were observed between rates in whites and Hispanics (Table). Conclusion: In a large insured population of patients with AF, we observed differences in rates of selected cardiovascular outcomes by sex and race. Additional research should explore the mechanisms underlying these differences and develop strategies to eliminate them.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

AbstractBackgroundRetinoblastoma binding protein 4 (Rbbp4) is a component of transcription regulatory complexes that control cell cycle gene expression. Previous work indicated that Rbbp4 cooperates with the Rb tumor suppressor to block cell cycle entry. Here, we use genetic analysis to examine the interactions of Rbbp4, Rb, and Tp53 in zebrafish neural progenitor cell cycle regulation and survival.ResultsRbbp4 is upregulated across the spectrum of human embryonal and glial brain cancers. Transgenic rescue of rbbp4 mutant embryos shows Rbbp4 is essential for zebrafish neurogenesis. Rbbp4 loss leads to apoptosis and γ‐H2AX in the developing brain that is suppressed by tp53 knockdown or maternal zygotic deletion. Mutant retinal neural precursors accumulate in M phase and fail to initiate G0 gene expression. rbbp4; rb1 mutants show an additive effect on the number of M phase cells. In rbbp4 mutants, Tp53 acetylation is detected; however, Rbbp4 overexpression did not rescue DNA damage‐induced apoptosis.ConclusionRbbp4 is necessary for neural progenitor cell cycle progression and initiation of G0 independent of Rb. Tp53‐dependent apoptosis in the absence of Rbpb4 correlates with Tp53 acetylation. Together these results suggest that Rbbp4 is required for cell cycle exit and contributes to neural progenitor survival through the regulation of Tp53 acetylation.

Introduction Although neurotization has the potential to improve sensory outcomes after autologous breast reconstruction, this technique remains controversial. There is debate regarding the clinical outcomes and the recipient nerve of choice. This histoanatomical study aims to quantitatively compare the sensory components of the recipient nerves involved in neurotization of the deep inferior epigastric perforator flap. Methods Subjects undergoing bilateral autologous breast reconstruction were enrolled. Transected nerve specimens underwent immunohistochemical staining with antibodies against neurofilament 1 and choline acetyltransferase for total and motor neurons within the axons, respectively. Photomicrographs were captured, and axons were analyzed using ImageJ. Sensory axons were calculated as equal to the difference between the total and cholinergic axonal counts. Results Thirty-eight nerves from 19 subjects were included. The overall mean sensory axon count was 1246.3 (±1171.9) in the lateral cutaneous branch (LCB) of the fourth intercostal nerve and 1123.8 (±1213.0) in the anterior cutaneous branch (ACB) of the third intercostal nerve. The fourth LCB presented with an additional 10.9% sensory axonal count (P > 0.05). On average, sensory fibers constituted 36.7% and 31.7% of all fibers in the third ACBs and fourth LCBs, respectively. Conclusions This study provides anatomic and histological evidence that the fourth LCB and third ACB contain comparable mean numbers of sensory axons. Both constitute adequate recipient nerves for coaptation in deep inferior epigastric perforator reinnervation to achieve optimal sensory return after breast reconstruction. The fourth LCB should be preferable when the third ACB remains intact to preserve any native breast flap sensation.

Background: Automated insulin delivery (AID) systems have not been evaluated in the context of psychological and pharmacological stress in type 1 diabetes. Our objective was to determine glycemic control and insulin use with Zone Model Predictive Control (zone-MPC) AID system enhanced for states of persistent hyperglycemia versus sensor-augmented pump (SAP) during outpatient use, including in-clinic induced stress. Materials and Methods: Randomized, crossover, 2-week trial of zone-MPC AID versus SAP in 14 adults with type 1 diabetes. In each arm, each participant was studied in-clinic with psychological stress induction (Trier Social Stress Test [TSST] and Socially Evaluated Cold Pressor Test [SECPT]), followed by pharmacological stress induction with oral hydrocortisone (total four sessions per participant). The main outcomes were 2-week continuous glucose monitor percent time in range (TIR) 70–180 mg/dL, and glucose and insulin outcomes during and overnight following stress induction. Results: During psychological stress, AID decreased glycemic variability percentage by 13.4% ( P = 0.009). During pharmacological stress, including the following overnight, there were no differences in glucose outcomes and total insulin between AID and physician-assisted SAP. However, with AID total user-requested insulin was lower by 6.9 U ( P = 0.01) for pharmacological stress. Stress induction was validated by changes in heart rate and salivary cortisol levels. During the 2-week AID use, TIR was 74.4% (vs. SAP 63.1%, P = 0.001) and overnight TIR was 78.3% (vs. SAP 63.1%, P = 0.004). There were no adverse events. Conclusions: Zone-MPC AID can reduce glycemic variability and the need for user-requested insulin during pharmacological stress and can improve overall glycemic outcomes. Clinical Trial Identifier NCT04142229.

AbstractBackgroundScreening for cognitive impairment is required at Medicare Annual Wellness Visits (AWV). Subjective or objective methods are suggested, but there is no one screening tool specified by Centers for Medicare and Medicaid Services (CMS). We assessed screening methods, its outcomes, and potential disparities in cognitive screening at AWV.MethodRetrospective chart reviews were done for 1,493 adults 55+ who had initial AWV at a single academic medical center ambulatory site between January 2011 and March 2017. Demographics, assessment type, and positive screens noted by provider were collected. Subjective assessments were by history/direct observation alone. Objective assessments are noted in Table 1. Multiple logistic regression with stepwise variable selection via AIC were done.ResultsMean age was 73.6 years (SD=7.9); 828 (55.5%) were female; 1191 (79.8%) were white (Table 2). 1,311 were screened for cognitive impairment, 120 were not screened, and 62 had an established diagnosis. Of those screened, 87.5% were screened using objective methods; greater age (p<0.001), African American race as compared to white race (p<0.001), and non‐English primary language (p=0.03) were associated with increased probability of positive screens. In subjective screening (n=163), speaking a non‐English primary language was associated with higher probability of positive screening (p = 0.04). In patients with positive screens through any method, 41 had no further cognitive assessment planned, 19 had plans for follow‐up, 15 were referred to neurology.ConclusionAWV are an opportunity to screen for underdiagnosed cognitive impairment. Clinicians in our study used a myriad of tests, despite each test’s unique limitations. Greater age, African American race, non‐English primary language being associated with increased probability of positive objective screening is consistent with the literature. In subjective screenings, patients with non‐English primary language were more likely to screen positive, suggesting that in AWV, non‐English speaking patients may be at a disadvantage for standard cognitive screening. Despite positive cognitive screening, the majority had no further cognitive assessment planned during the visit. Our study suggests that more research should focus on a standardized cognitive screening and decision making after a positive cognitive screening at AWV.

Abstract Background Decreasing pain catastrophizing and improving self-efficacy to self-manage chronic pain symptoms are important treatment targets in the context of interdisciplinary pain rehabilitation. Greater pain catastrophizing has been shown to be associated with greater impact of pain symptoms on functioning; conversely, greater pain self-efficacy has been associated with lower pain intensity and lower levels of disability. Objective To prospectively evaluate interdisciplinary pain rehabilitation outcomes, as well as to evaluate the mediating effects of both pain catastrophizing and pain self-efficacy on outcome. Methods Participants were 315 patients with chronic pain between April 2017 and April 2018 who completed a 3-week interdisciplinary pain rehabilitation program. Pain severity, pain interference, pain catastrophizing, pain self-efficacy, quality of life, depressive symptom questionnaires, and measures of physical performance were assessed before and after treatment. Follow-up questionnaires were returned by 163 participants. Effect size and reliable change analyses were conducted from pre- to posttreatment and from pretreatment to 6-month follow-up. Mediation analyses were conducted to determine the mediating effect of pain catastrophizing and pain self-efficacy on pain outcome. Results Significant improvements from pre- to posttreatment in pain outcomes were observed, and more than 80% evidenced a reliable change in at least one pain-relevant measure. Pain catastrophizing and pain self-efficacy mediated the relationship between changes in pain outcomes. Conclusions Interdisciplinary pain rehabilitation is an effective treatment, and decreasing pain catastrophizing and increasing pain self-efficacy can influence maintenance of treatment gains.