Abstract Introduction While REM sleep without atonia (RSWA) in REM sleep behavior disorder (RBD) is associated with male sex, age greater than or equal to 50 years, alpha-synucleinopathies, and narcolepsy, the characteristics of patients with RSWA/persistent periodic limb movements of sleep in REM sleep (RSWA/PLMS-REM) without dream enactment behaviors are unexplored. The aim of this study was to compare the demographics, comorbidities, and concomitant medication use between RSWA/PLMS-REM patients and non-RSWA/non-PLMS-REM controls. Based on anecdotal clinical observations, we hypothesized that these patients are more commonly young, women, have psychiatric or neurological diseases, and use antidepressants. Methods We conducted a retrospective review of the Mayo Clinic electronic medical record to identify all patients with RSWA/PLMS-REM between November 2018 and November 2020. After excluding all patients with RBD, restless legs syndrome, narcolepsy, and RSWA/non-PLMS-REM, we identified 27 patients. All in-lab polysomnograms (PSGs) were reviewed to calculate the periodic limb movement index per hour of REM sleep (REM-PLMI). We also identified a control group of 15 individuals without RSWA, reviewed their PSGs, and calculated the REM-PLMI. Results The mean REM-PLMI of patients with RSWA was 64 +/- 8.3 (standard error of mean (SEM)) per hour versus 1 +/- 0.6 (SEM) per hour in non-RSWA controls (p < 0.001). Patients with RSWA/PLMS-REM and non-RSWA controls had similar age and gender, 62 +/- 3 (SEM) versus 58 +/- 3 (SEM) years and 81% versus 87% men, respectively. However, psychiatric diagnosis, neurological disorders, and antidepressants use were more common among RSWA/PLMS-REM patients compared to non-RSWA controls with p = 0.0002, p = 0.0035 and p = 0.0074 respectively (Fisher’s Exact Test). Conclusion Psychiatric diagnosis, neurological disorders, and antidepressant use are more common among RSWA/PLMS-REM patients compared to non-RSWA/non-PLMS-REM controls. Further research to determine the implications of a diagnosis of RSWA/PLMS-REM for the future development of alpha-synucleinopathies are needed and currently ongoing. Support (if any):
533 Characteristics of patients with REM sleep without atonia (RSWA)/persistent periodic limb movements of sleep (PLMS) in REM sleep
Abstract Introduction While RSWA in REM sleep behavior disorder (RBD) is associated with male sex, age > 50 years, alpha-synucleinopathies, and narcolepsy, the characteristics of patients with RSWA/PLMS in REM sleep (RSWA/PLMS-REM) without dream enactment behaviors are unexplored. The aim of this study was to compare the demographics, comorbidities and concomitant medication use between RSWA/PLMS-REM patients and non-RSWA/non-PLMS-REM controls. Based on anecdotal clinical observations we hypothesized that these patients are more commonly young, women, have psychiatric or neurological diseases, and use antidepressants. Methods We conducted a retrospective review of the Mayo Clinic electronic medical record to identify all patients with RSWA/ PLMS-REM between November 2018 and November 2020. After excluding all patients with RBD, restless legs syndrome, narcolepsy and RSWA/non-PLMS-REM we identified 27 patients. All PSGs were reviewed to calculate the periodic limb movement index per hour of REM sleep (REM-PLMI). We also identified a covenience sample of 15 non-RSWA controls, reviewed their PSGs and calculated REM-PLMI. Results The mean REM-PLMI of patients with RSWA was 64+/-8.3 (SEM)/hour versus 1+/-0.6 (SEM)/hours in non-RSWA controls (p< 0.001). Patients with RSWA/PLMS-REM and non-RSWA controls had similar age and gender, 62 +/- 3 (SEM) versus 58 +/-3 (SEM) years and 81% versus 87% men, respectively. However psychiatric diagnosis, neurological disorders and antidepressants use was more common among RSWA/PLMS-REM patients compared to non-RSWA controls, p=0.0002, p=0.0035 and p=0.0074, respectively. (Fisher’s Exact Test) Conclusion Psychiatric diagnosis, neurological disorders and antidepressant use are more common among RSWA/PLM-REM patients compared to non-RSWA controls. Further research to determine the implications of a diagnosis of RSWA/PLMS-REM for the future development of alpha-synucleinopathies are needed and currently ongoing. Support (if any):
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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Abstract Introduction As cerebrospinal fluid (CSF) neurofilament light protein (NfL) and the CSF/serum albumin ratio (Q Alb ) are used in the clinical routine, the impact of demographic factors on these biomarkers is important to understand. Methods Participants were derived from two Swedish samples: the population‐based H70 Study (n = 308, age 70) and a clinical routine cohort (CSF NfL, n = 8995, Q Alb , n = 39252, age 0 to 95). In the population‐based study, Q Alb and NfL were examined in relation to sex, cardiovascular risk factors, and cerebral white matter lesions (WMLs). In the clinical cohort, Q Alb and NfL sex differences were tested in relation to age. Results Men had higher Q Alb and NfL concentrations and had higher Q Alb and NfL concentrations from adolescence throughout life. NfL was not related to WML, but Q Alb correlated positively with WMLs. Discussion The CSF NfL sex difference could not be explained by vascular pathology. Future studies should consider using different reference limits for men and women.
Reparative Cell Therapy for the Heart: Critical Internal Appraisal of the Field in Response to Recent Controversies
Abstract The concept that cell-based repair of myocardial injury might be possible was introduced almost two decades ago; however, the field of cardiovascular reparative medicine has been criticized as translation to clinically effective approaches has been slow. The recent retraction of a series of papers has further impacted perception of this area of research. As researchers, clinicians, and teachers in this field, we felt it incumbent to critically appraise the current state of cardiac cell repair, determine what can be learned from past mistakes, and formulate best practices for future work. This special communication summarizes an introspective assessment of what has fallen short, how to prevent similar issues, and how the field might best move forward in the service of science and patients.
Abstract PS13-09: Chemotherapy-induced nausea and vomiting (CINV) risk after prior breakthrough CINV: Unmasking the false average
Abstract Background: Although many studies have demonstrated consistent levels of effectiveness of CINV prophylaxis for the entire study population across multiple chemotherapy cycles, rarely have studies reported how each patient’s risk of subsequent CINV differs based on prior cycle breakthrough CINV with the same prophylaxis. We lack data on whether prophylaxis continues to fail in the same group of patients each cycle, or whether failure is random with each subsequent cycle. We sought to evaluate individual patients’ risk of repeat CINV in each subsequent chemotherapy cycle. Methods: In a prospective, 4-cycle CINV prophylaxis trial of oral or intravenous combination netupitant/palonosetron (NEPA) + dexamethasone (day 1) for patients with breast cancer receiving anthracycline + cyclophosphamide (AC), we defined CINV as vomiting or use of rescue medication during days 1-5 after chemotherapy. Patients without CINV were classified as complete response (CR); the rest as treatment failure (TF). We analyzed patients’ sequences of CR and TF, and compared CR or TF for cycles 2-4 based on cycle 1 outcomes, using chi-square statistics. To provide context, we performed a post-hoc similar analysis of results reported by Herrstedt et al [2005] from a clinical trial of ondansetron + aprepitant (APR) for patients with breast cancer receiving 4 cycles of AC. Results: The 402 female patients in the NEPA trial received a total of 1,299 cycles. In cycle 1, 99 (24.6%) patients experienced TF (TF1); over all 4 cycles, TF occurred 253 times (19.5%). Patients with CR in cycle 1 (CR1) had a ≥92% rate of CR in cycle 2; their rates of repeat CR were similar in each subsequent cycle. Patients with TF1 had nearly equal risk of CR or TF in cycle 2 (45:55); thereafter 85% of this TF1 subgroup repeated their cycle 2 outcome (CR or TF) in cycles 3 and 4. Over all cycles of NEPA, patients with CR1 subsequently had CR in >90% of cycles 2-4; those with TF1 subsequently had TF in 49.8% of cycles 2-4 (p<0.0001) (see Table). We separately examined Herrstedt’s evaluation of 433 patients across 1537 cycles with APR. In cycle 1, TF was seen 213 times (49.2%), with TF reported in 46.7% of cycles 1-4. We found that patients with CR1 had an 80.5% rate of CR in cycle 2 and repeat CR rates were higher in subsequent cycles. Patients with TF1 had TF in cycle 2 (TF2) at a rate of 78.4%, with 76.6% TF3 and 72.7% TF4. For APR, CR1 resulted in subsequent CR in 78.6% of cycles 2-4 while patients with TF1 again had TF in 74.8% of cycles 2-4 (p<0.0001). Patients with TF1 were more likely to later drop from the study (see Table). Notably, among those with CR1 after APR, the few patients who later had TF in any cycle, had a subsequent repeat failure rate similar to those with TF1. Conclusions: When patients receiving guideline-recommended triple antiemetic prophylaxis successfully avoided CINV in their first cycle of HEC, they had 80-95% likelihood of repeating that success in later cycles. After NEPA, those whose prophylaxis failed in cycle 1 did not face a similar high risk of repeat failure in cycle 2. The pattern of repeat failure after aprepitant was different, with a high repeat failure risk starting in cycle 2. These findings strongly suggest that consistent population average CR rates reported across cycles may mask a higher repeat failure rate for individual patients that experience cycle 1 CINV, particularly for aprepitant. Further study of this phenomenon is needed for other HEC regimens, and to confirm the lack of high repeat failure seen in cycle 2 for NEPA. Repeat CINV in Later Cycles, Based on Cycle 1 ResultsNEPAAprepitant + OndansetronInitial Cycle Result (n/total initial cycles)CR1 (303/402)TF1 (99/402)CR1 vs TF1 (P value)CR1 (220/433)TF1 (213/433)CR1 vs TF1 (P value)Subsequent CR cycles (n, % of total subseq. cycles)636 (93.0%)107 (50.2%)<0.0001464 (78.6%)124 (25.2%)<0.0001Subsequent TF cycles (n, % of total subseq. cycles)48 (7.0%)106 (49.8%)126 (21.4%)370 (74.8%)Total subsequent cycles (n, % of total subseq. cycles)684 (100%)213 (100%)590 (100%)494 (100%)Dropped vs ITT* (n, % ITT cycles)225 (24.8%)84 (28.3%)0.226370 (10.6%)145 (22.7%)<0.0001* The NEPA trial was closed when the last patient completed the first cycle, resulting in an artificially high proportion of patients that did not complete 4 cycles. Citation Format: Rudolph M Navari, Gary Binder, Alexander Molassiotis, Eric Roeland, Kathryn J. Ruddy, Thomas W. LeBlanc, Dwight D. Kloth, Silvia Sebastiani, Lina Y. Dimberg, Luke M. Schmerold, Xing Liu, Lee Schwartzberg. Chemotherapy-induced nausea and vomiting (CINV) risk after prior breakthrough CINV: Unmasking the false average [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-09.
Utility of the CHA2DS2-VASc score for predicting ischaemic stroke in patients with or without atrial fibrillation: a systematic review and meta-analysis
Abstract Aims Anticoagulants are the mainstay treatment for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), and the CHA2DS2-VASc score is widely used to guide anticoagulation therapy in this cohort. However, utility of CHA2DS2-VASc in NVAF patients is debated, primarily because it is a vascular scoring system, which does not incorporate atrial fibrillation related parameters. Therefore, we conducted a meta-analysis to estimate the discrimination ability of CHA2DS2-VASc in predicting ischaemic stroke overall, and in subgroups of patients with or without NVAF. Methods and results PubMed and Embase databases were searched till June 2020 for published articles that assessed the discrimination ability of CHA2DS2-VASc, as measured by C-statistics, during mid-term (2–5 years) and long-term (>5 years) follow-up. Summary estimates were reported as random effects C-statistics with 95% confidence intervals (CIs). Seventeen articles were included in the analysis. Nine studies (n = 453 747 patients) reported the discrimination ability of CHA2DS2-VASc in NVAF patients, and 10 studies (n = 138 262 patients) in patients without NVAF. During mid-term follow-up, CHA2DS2-VASc predicted stroke with modest discrimination in the overall cohort [0.67 (0.65–0.69)], with similar discrimination ability in patients with NVAF [0.65 (0.63–0.68)] and in those without NVAF [0.69 (0.68–0.71)] (P-interaction = 0.08). Similarly, at long-term follow-up, CHA2DS2-VASc had modest discrimination [0.66 (0.63–0.69)], which was consistent among patients with NVAF [0.63 (0.54–0.71)] and those without NVAF [0.67 (0.64–0.70)] (P-interaction = 0.39). Conclusion This meta-analysis suggests that the discrimination power of the CHA2DS2-VASc score in predicting ischaemic stroke is modest, and is similar in the presence or absence of NVAF. More accurate stroke prediction models are thus needed for the NVAF population.
Bur Hole–Based Resections of Intrinsic Brain Tumors with Exoscopic Visualization
AbstractBackground The primary goal of brain tumor surgery is maximal safe resection while avoiding iatrogenic injury. As surgical technology increases, it is becoming more possible to resect these lesions using minimally invasive approaches. While keyhole surgeries are being advocated, the lower limit of these approaches is unclear. Bur hole–based approaches may represent a standardized minimally invasive approach. The exoscope may provide increased visualization over standard microscopic visualization, making this approach possible. This approach has yet to be described strictly for intra-axial brain tumors.Material and Methods All patients who underwent a bur hole–based surgery of an intra-axial tumor with exoscopic visualization by the senior author from January 2018 to December 2019 were prospectively identified and patient information and outcomes were collected.Results Fifteen consecutive patients underwent surgical resection of an intrinsic brain tumor using a bur hole–based approach with exoscopic visualization. The average ± standard deviation age was 57.9 ± 24.2 years. The pathology was a metastatic brain tumor in eight patients (53%), low-grade glioma in four patients (27%), and high-grade glioma in three patients (20%). The average percent resection was 100 ± 1%, where 14 (93%) underwent gross total resection. Following surgery, the median (interquartile range) Karnofsky performance scale (KPS) score was 90 (90–90), where 11 (73%) and four patients (27%) had improved and stable KPS, respectively. Zero patients had complications. The average length of stay following surgery was 1.4 ± 0.5 days, where nine patients (60%) were discharged on postoperative day 1.Conclusion This study shows that intra-axial tumors can be resected through a bur hole–based approach with exoscopic visualization with extensive resection, minimal morbidity, and early discharge rates.
Sex differences in CSF biomarkers for neurodegeneration and blood‐brain barrier integrity
AbstractBackgroundCSF neurofilament light protein (NfL) is an important biomarker in several neurologic diseases. CSF NfL concentrations are known to increase with age, but sex differences have been less examined. The CSF/serum albumin ratio (QAlb) is a biomarker for blood‐brain barrier integrity, which has previously been found to be higher in men. As NfL and QAlb are used in clinical routine, the impact of demographic factors on these biomarkers is important to understand.MethodParticipants were derived from two samples. The first was a population‐based cohort of 308 70‐year olds from the Gothenburg H70 Birth Cohort Study, Sweden. The second data set comprised CSF NfL and QAlb results from 8995 and 39252 subjects respectively, generated in clinical practice between 2005‐2012 in Gothenburg, Sweden. In the population‐based study, QAlb and NfL concentrations were examined in relation to sex, cardiovascular risk factors, and MRI signs of cerebral white matter lesions. In the clinical routine cohort, sex differences in QAlb and NfL were tested in relation to age.ResultIn the population‐based sample, men had higher QAlb and NfL concentrations than women. NfL was not related to cerebral vascular pathology, but QAlb correlated positively with several measures of white matter lesions. In the clinical routine cohort, men also had higher QAlb and NfL concentrations from adolescence and throughout life.ConclusionQAlb ratios and CSF NfL levels are higher in men throughout life. The CSF NfL sex difference could not be explained by vascular pathology. Future studies should consider using different reference limits for men and women.