Participant-reported personal utility of genetic testing for Parkinson's disease and interest in clinical trial participation.

Genetic testing for Parkinson's disease (PD) is infrequently performed due to perceptions of low utility. We investigated the personal utility in PD GENEration and how results lead to enrollment in additional research studies. Participants (n = 972) underwent genetic testing, results disclosure, genetic counseling, and completed a survey examining the perceived personal utility of their results and interest in participating in additional studies. Most participants found their genetic test results useful, including satisfying curiosity (81%), feeling good about helping the medical community (80%), and having information to share with family (77%). There were no significant differences in responses based on result type. Forty-five percent of participants expressed interest in participating in research studies; whereas 16% of participants confirmed enrollment. Our results suggest that participants find personal utility in genetic testing regardless of results. Although participants may be interested in enrolling in additional research, they may need support and resources.

Improving Parkinson's Disease Care through Systematic Screening for Depression.

BACKGROUND: Depression is common in Parkinson's disease (PD) but is underrecognized clinically. Although systematic screening is a recommended strategy to improve depression recognition in primary care practice, it has not been widely used in PD care. METHODS: The 15-item Geriatric Depression Scale (GDS-15) was implemented at 5 movement disorders clinics to screen PD patients. Sites developed processes suited to their clinical workflow. Qualitative interviews with clinicians and patients provided information on feasibility, acceptability, and perceived utility. RESULTS: Prior to implementation, depression screening was recorded in 12% using a formal instrument; 64% were screened informally by clinical interview, and no screening was recorded in 24%. Of 1406 patients seen for follow-up care during the implementation period, 88% were screened, 59% using the GDS-15 (self-administered in 51% and interviewer administered in 8%), a nearly 5-fold increase in formal screening. Lack of clinician or staff time and inability to provide the GDS-15 to the patient ahead of the visit were the most commonly cited reasons for lack of screening using the GDS-15; 378 (45%) patients completing the GDS-15 screened positive for depression, and 137 were enrolled for a 12-month prospective follow-up. Mean GDS-15 scores improved from 8.8 to 7.0 (P < 0.0001) and the 39-item Parkinson's Disease Questionnaire emotional subscore from 42.2 to 36.7 (P = 0.0007). CONCLUSIONS: Depression screening in PD using a formal instrument can be achieved at much higher levels than is currently practiced, but there are barriers to implementing this in clinical practice. An individual site-specific process is necessary to optimize screening rates.

Parkinson's disease variant detection and disclosure: PD GENEration, a North American study.

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's disease. PD GENEration is an ongoing multi-centre, observational study (NCT04057794, NCT04994015) offering genetic testing with results disclosure and genetic counselling to those in the US (including Puerto Rico), Canada and the Dominican Republic, through local clinical sites or remotely through self-enrolment. DNA samples are analysed by next-generation sequencing including deletion/duplication analysis (Fulgent Genetics) with targeted testing of seven major Parkinson's disease-related genes. Variants classified as pathogenic/likely pathogenic/risk variants are disclosed to all tested participants by either neurologists or genetic counsellors. Demographic and clinical features are collected at baseline visits. Between September 2019 and June 2023, the study enrolled 10 510 participants across >85 centres, with 8301 having received results. Participants were: 59% male; 86% White, 2% Asian, 4% Black/African American, 9% Hispanic/Latino; mean age 67.4 ± 10.8 years. Reportable genetic variants were observed in 13% of all participants, including 18% of participants with one or more 'high risk factors' for a genetic aetiology: early onset (<50 years), high-risk ancestry (Ashkenazi Jewish/Basque/North African Berber), an affected first-degree relative; and, importantly, in 9.1% of people with none of these risk factors. Reportable variants in GBA1 were identified in 7.7% of all participants; 2.4% in LRRK2; 2.1% in PRKN; 0.1% in SNCA; and 0.2% in PINK1, PARK7 or VPS35 combined. Variants in more than one of the seven genes were identified in 0.4% of participants. Approximately 13% of study participants had a reportable genetic variant, with a 9% yield in people with no high-risk factors. This supports the promotion of universal access to genetic testing for Parkinson's disease, as well as therapeutic trials for GBA1 and LRRK2-related Parkinson's disease.

Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss.

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3aR878H/+ bone marrow (BM) cells resulted in clonal expansion of mutant cells into both myeloid and lymphoid lineages and an elevated abundance of osteoclast precursors in the BM and osteoclastogenic macrophages in the periphery. DNMT3A-driven clonal hematopoiesis in recipient mice promoted naturally occurring periodontitis and aggravated experimentally induced periodontitis and arthritis, associated with enhanced osteoclastogenesis, IL-17-dependent inflammation and neutrophil responses, and impaired regulatory T cell immunosuppressive activity. DNMT3A-driven clonal hematopoiesis and, subsequently, periodontitis were suppressed by rapamycin treatment. DNMT3A-driven CHIP represents a treatable state of maladaptive hematopoiesis promoting inflammatory bone loss.

A Deep Learning Framework for Predicting Patient Decannulation on Extracorporeal Membrane Oxygenation Devices: Development and Model Analysis Study.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a therapy for patients with refractory respiratory failure. The decision to decannulate someone from extracorporeal membrane oxygenation (ECMO) often involves weaning trials and clinical intuition. To date, there are limited prognostication metrics to guide clinical decision-making to determine which patients will be successfully weaned and decannulated. OBJECTIVE: This study aims to assist clinicians with the decision to decannulate a patient from ECMO, using Continuous Evaluation of VV-ECMO Outcomes (CEVVO), a deep learning-based model for predicting success of decannulation in patients supported on VV-ECMO. The running metric may be applied daily to categorize patients into high-risk and low-risk groups. Using these data, providers may consider initiating a weaning trial based on their expertise and CEVVO. METHODS: Data were collected from 118 patients supported with VV-ECMO at the Columbia University Irving Medical Center. Using a long short-term memory-based network, CEVVO is the first model capable of integrating discrete clinical information with continuous data collected from an ECMO device. A total of 12 sets of 5-fold cross validations were conducted to assess the performance, which was measured using the area under the receiver operating characteristic curve (AUROC) and average precision (AP). To translate the predicted values into a clinically useful metric, the model results were calibrated and stratified into risk groups, ranging from 0 (high risk) to 3 (low risk). To further investigate the performance edge of CEVVO, 2 synthetic data sets were generated using Gaussian process regression. The first data set preserved the long-term dependency of the patient data set, whereas the second did not. RESULTS: CEVVO demonstrated consistently superior classification performance compared with contemporary models (P<.001 and P=.04 compared with the next highest AUROC and AP). Although the model's patient-by-patient predictive power may be too low to be integrated into a clinical setting (AUROC 95% CI 0.6822-0.7055; AP 95% CI 0.8515-0.8682), the patient risk classification system displayed greater potential. When measured at 72 hours, the high-risk group had a successful decannulation rate of 58% (7/12), whereas the low-risk group had a successful decannulation rate of 92% (11/12; P=.04). When measured at 96 hours, the high- and low-risk groups had a successful decannulation rate of 54% (6/11) and 100% (9/9), respectively (P=.01). We hypothesized that the improved performance of CEVVO was owing to its ability to efficiently capture transient temporal patterns. Indeed, CEVVO exhibited improved performance on synthetic data with inherent temporal dependencies (P<.001) compared with logistic regression and a dense neural network. CONCLUSIONS: The ability to interpret and integrate large data sets is paramount for creating accurate models capable of assisting clinicians in risk stratifying patients supported on VV-ECMO. Our framework may guide future incorporation of CEVVO into more comprehensive intensive care monitoring systems.

Efficacy of sintered Zinc-doped fluorapatite scaffold as an antimicrobial regenerative bone filler for dental applications.

OBJECTIVES: The objective of this study was to assess whether zinc-doped fluorapatite (ZnFA) could serve as an effective antimicrobial dental bone filler for bone regeneration compared to autografts. METHODS: FA and 2 % zinc-doped FA (2ZnFA) were synthesized and characterized in-house. Compressed and sintered FA and 2ZnFA disks were incubated with bacteria to assess antimicrobial properties. Adipose-derived stem cells were cultured on these discs to evaluate the surfaces' ability to support cell growth and promote osteogenic differentiation. Surfaces exhibiting the highest expressions of the bone markers osteopontin and osteocalcin were selected for an in vivo study in a rat mandibular defect model. Twenty rats were divided into 5 groups, equally, and a 5 mm surgical defect of the jaw was left untreated or filled with 2ZnFA, FA, autograft, or demineralized bone matrix (DBM). At 12 weeks, the defects and surrounding tissues were harvested and subjected to microCT and histological evaluations. RESULTS: Standard techniques such as FTIR, ICP-MS, fluoride probe, and XRD revealed the sintered FA and ZnFA's chemical compositions and structures. Bacterial studies revealed no significant differences in surface bacterial adhesion properties between FA and 2ZnFA, but significantly fewer bacterial loads than control titanium discs (p < 0.05). Cell culture data confirmed that both surfaces could support cell growth and promote the osteogenic differentiation of stem cells. MicroCT analysis confirmed statistical similarities in bone regeneration within FA, 2ZnFA, and autograft groups. CONCLUSION: The data suggests that both FA and 2ZnFA could serve as alternatives to autograft materials, which are the current gold standard. Moreover, these bone fillers outperformed DBM, an allograft material commonly used as a dental bone void filler. CLINICAL SIGNIFICANCE: The use of FA or 2ZnFA for treating mandibular defects led to bone regeneration statistically similar to autograft repair and significantly outperformed the widely used dental bone filler, DBM. Additional translational research may confirm FA-based materials as superior substitutes for existing synthetic bone fillers, ultimately enhancing patient outcomes.

Acute liver failure.

ABSTRACT: Acute liver failure, commonly caused by acetaminophen overdose, is associated with numerous systemic complications including cerebral edema, hypotension, acute kidney injury, and infection. Management is primarily supportive, with an emphasis on excellent neurocritical care. Although some antidotes and targeted treatments exist, the only definitive treatment remains orthotopic liver transplant.

Association between blood markers and the progression of osseointegration in percutaneous prostheses patients-A pilot study.

Patients implanted with osseointegrated (OI) prosthetic systems have reported vastly improved upper and lower extremity prosthetic function compared with their previous experience with socket-suspension systems. However, OI systems have been associated with superficial and deep-bone infections and implant loosening due, in part, to a failure of the osseointegration process. Although monitoring the osseointegration using circulating biomarkers has clinical relevance for understanding the progression of osseointegration with these devices, it has yet to be established. Ten patients were enrolled in this study. Blood samples were collected at pre-selected times, starting before implantation surgery, and continuing to 12 months after the second surgery. Bone formation markers, bone resorption markers, and circulating amino acids were measured from blood samples. A linear mixed model was generated for each marker, incorporating patient ID and age with the normalized marker value as the response variable. Post hoc comparisons were made between 1 week before Stage 1 Surgery and all subsequent time points for each marker, followed by multiple testing corrections. Serial radiographic imaging of the residual limb containing the implant was obtained during follow-up, and the cortical index (CI) was calculated for the bone at the porous region of the device. Two markers of bone formation, specifically bone-specific alkaline phosphatase (Bone-ALP) and amino-terminal propeptide of type I procollagen (PINP), exhibited significant increases when compared with the baseline levels of unloaded residual bone prior to the initial surgery, and they subsequently returned to their baseline levels by the 12-month mark. Patients who experienced clinically robust osseointegration experienced increased cortical bone thickness at the porous coated region of the device. A medium correlation was observed between Bone-ALP and the porous CI values up to PoS2-M1 (p = .056), while no correlation was observed for PINP. An increase in bone formation markers and the lack of change observed in bone resorption markers likely reflect increased cortical bone formation induced by the end-loading design of the Utah OI device used in this study. A more extensive study is required to validate the correlation observed between Bone-ALP and porous CI values.

DRESS syndrome: More than just a rash.

ABSTRACT: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is rare but carries significant mortality and morbidity, making early identification and definitive management crucial. The diagnosis of DRESS is made clinically and involves consideration of a broad list of differential diagnoses. Given variable clinical presentations among patients with DRESS syndrome, clinicians should look for common findings and other hallmarks of the syndrome while monitoring for known complications. Additionally, clinicians should maintain a high index of suspicion to avoid missing more mild presentations, such as in this case patient with DRESS syndrome minor.

Sintered fluorapatite scaffolds as an autograft-like engineered bone graft.

Hydroxyapatite (HA)-based materials are widely used as bone substitutes due to their inherent biocompatibility, osteoconductivity, and bio-absorption properties. However, HA scaffolds lack compressive strength when compared to autograft bone. It has been shown that the fluoridated form of HA, fluorapatite (FA), can be sintered to obtain this desired strength as well as slower degradation properties. Also, FA surfaces have been previously shown to promote stem cell differentiation toward an osteogenic lineage. Thus, it was hypothesized that FA, with and without stromal vascular fraction (SVF), would guide bone healing to an equal or better extent than the clinical gold standard. The regenerative potentials of these scaffolds were tested in 32 Lewis rats in a femoral condylar defect model with untreated (negative), isograft (positive), and commercial HA as controls. Animals were survived for 12 weeks post-implantation. A semi-quantitative micro-CT analysis was developed to quantify the percent new bone formation within the defects. Our model showed significantly higher (p < .05) new bone depositions in all apatite groups compared to the autograft group. Overall, the FA group had the most significant new bone deposition, while the differences between HA, FA, and FA + SVF were insignificant (p > .05). Histological observations supported the micro-CT findings and highlighted the presence of healthy bone tissues without interposing capsules or intense immune responses for FA groups. Most importantly, the regenerating bone tissue within the FA + SVF scaffolds resembled the architecture of the surrounding trabecular bone, showing intertrabecular spaces, while the FA group presented a denser cortical bone-like architecture. Also, a lower density of cells was observed near FA granules compared to HA surfaces, suggesting a reduced immune response. This first in vivo rat study supported the tested hypothesis, illustrating the utility of FA as a bone scaffold material.

Dental Caries, Race and Incident Ischemic Stroke, Coronary Heart Disease, and Death.

BACKGROUND: Dental caries is a highly prevalent disease worldwide. In the United States, untreated dental caries is present in >1 in 5 adults. The objective of this study was to determine the relationship between dental caries and incident ischemic stroke, coronary heart disease (CHD) events, and death. METHODS: The dental cohort (n=6351) of the ARIC study (Atherosclerosis Risk in Communities) was followed for incident ischemic stroke, CHD event, and all-cause mortality. Of all the participants at visit 4 (n=11 656), those who were unable to go through dental examination, or with prevalent ischemic stroke and CHD events, were excluded. The full-mouth dental examination was conducted at visit 4 (1996-1998), assessing dental caries. The dose response of decayed, missing, and filled surfaces due to caries was assessed and related to the outcome. Outcomes were assessed through the end of 2019. Additionally, the effect of regular dental care utilization on dental caries was evaluated. RESULTS: Participants with ≥1 dental caries had an increased risk of stroke (adjusted hazard ratio [HR], 1.40 [95% CI, 1.10-1.79]) and death (adjusted HR, 1.13 [95% CI, 1.01-1.26]) but not for CHD events (adjusted HR, 1.13 [95% CI, 0.93-1.37]). The association of dental caries and ischemic incident stroke was significantly higher in the African American population compared with the White subgroup (interaction term P=0.0001). Increasing decayed, missing, and filled surfaces were significantly associated with stroke (adjusted HR, 1.006 [95% CI, 1.001-1.011]) and death (adjusted HR, 1.003 [95% CI, 1.001-1.005]) but not CHD (adjusted HR, 1.002 [95% CI, 1.000-1.005]). Regular dental care utilization lowered (adjusted odds ratio, 0.19 [95% CI, 0.16-0.22]; P<0.001) the chance of caries. CONCLUSIONS: Among the cohort, dental caries was independently associated with the risk of ischemic stroke and death, with the effect higher in African American participants. Regular dental care utilization was associated with a lower chance of caries, emphasizing its relevance in the prevention of these events.

Dental Caries a Risk Factor for Intracerebral Hemorrhage.

INTRODUCTION: Streptococcus mutans is a known cause of dental caries that contains a collagen-binding protein, Cnm, and exhibits inhibition of platelet aggregation and matrix metalloproteinase-9 activation. This strain has been linked to aggravation of experimental intracerebral hemorrhage (ICH) and may be a risk factor for ICH. The purpose of this study was to test the association between dental caries and incident ICH. METHODS: The presence of dental caries and periodontal disease was assessed in subjects from the Dental Atherosclerosis Risk in Communities (DARIC) study without prior stroke or ICH. This cohort was followed for incident ICH over a period of 10 years. Cox regression was used to compute crude and adjusted hazards ratio from the dental assessment. RESULTS: Among 6,315 subjects, dental surface caries and/or root caries were recorded in 1,338 (27%) subjects. Of those, 7 (0.5%) had incident ICH over a period of 10 years following the visit 4 assessment. Of the remaining 4,977 subjects, 10 (0.2%) had incident ICH. Those with dental caries versus those without dental caries were slightly younger (mean age 62.0 ± 5.7 vs. 62.4 ± 5.6, p = 0.012), had a greater proportion of males (51 vs. 44%, p < 0.001), African Americans (44 vs. 10%, p < 0.001), and were hypertensive (42 vs. 31%, p < 0.001). The association between caries and ICH was significant (crude HR 2.69, 95% CI 1.02-7.06) and strengthened after adjustment for age, gender, race, education level, hypertension, and periodontal disease (adjusted HR 3.88, 95% CI 1.34-11.24). CONCLUSION: Dental caries is a potential risk for incident ICH after caries detection. Future studies are needed to determine if treatment of dental caries can reduce the risk of ICH.

Association of Dental Infections with Intracranial Atherosclerotic Stenosis.

INTRODUCTION: Periodontal disease (PD) and dental caries are oral infections leading to tooth loss that are associated with atherosclerosis and cerebrovascular disease. We assessed the hypothesis that PD and caries are associated with asymptomatic intracranial atherosclerosis (ICAS) in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: Full-mouth clinical periodontal measurements (7 indices) collected at 6 sites per tooth from 6,155 subjects from the Dental Atherosclerosis Risk in Communities Study (DARIC) without prior stroke were used to differentiate seven PD stages (Periodontal Profile Class [PPC]-I to -VII) and dental caries on coronal dental surface (DS) and dental root surface (DRS). A stratified subset underwent 3D time-of-flight MR angiogram and 3D high isotropic-resolution black blood MRI. ICAS was graded according to the criteria established by the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. We evaluated the relationship between PD stage and dental caries with asymptomatic ICAS, graded as no ICAS, <50% ICAS, and ≥50% ICAS. RESULTS: Among dentate subjects who underwent vascular imaging, 801 (70%) had no ICAS, 232 (20%) had <50% ICAS, and 112 (10%) had ≥50% ICAS. Compared to participants without gum disease (PPC-I), participants with mild-moderate tooth loss (PPC-VI), severe tooth loss (PPC-VII), and severe PD (PPC-IV) had higher odds of having <50% ICAS. Participants with extensive gingivitis (PPC-V) had significantly higher odds of having ≥50% ICAS. This association remained significant after adjusting for confounding variables: age, gender, race, hypertension, diabetes, dyslipidemia, 3-level education, and smoking status. There was no association between dental caries (DS and DRS) and ICAS <50% and ≥50%. CONCLUSION: We report significant associations between mild-moderate tooth loss, severe tooth loss, and severe PD with <50% ICAS as well as an association between extensive gingivitis and ≥50% ICAS. We did not find an association between dental caries and ICAS.

Acute kidney injury during extracorporeal life support in cardiogenic shock: Does flow matter?

BACKGROUND: This study examines the role of extracorporeal life support flow in the development of acute kidney injury in cardiogenic shock. METHODS: We performed a retrospective analysis of 465 patients placed on extracorporeal life support at our institution between January 2015 and December 2020 for cardiogenic shock. Flow index was calculated by dividing mean flow by body surface. Stages of acute kidney injury were determined according to Kidney Disease: Improving Global Outcomes (KDIGO) organization guidelines. RESULTS: There were 179 (38.5%) patients who developed acute kidney injury, 63.1% of which were classified as Stage 3--the only subgroup associated with 1-year mortality (hazard ratio = 2.03, p < .001). Risk of kidney injury increased up to a flow index of 1.6 L/min/m2, and kidney injury was more common among patients with flow index greater than 1.6 L/min/m2 (p = .034). Those with kidney injury had higher baseline lactate levels (4.4 vs 3.1, p = .04), and Stage 3 was associated wit higher baseline creatinine (p < .001). CONCLUSIONS: In our cohort, kidney injury was common and Stage 3 kidney injury was associated with worse outcomes compared to other stages. Low flow was not associated with increased risk of kidney injury. Elevated baseline lactate and creatinine among patients with acute kidney injury suggest underlying illness severity, rather than flow, may influence kidney injury risk.

Periodontal Disease Treatment After Stroke or Transient Ischemic Attack: The PREMIERS Study, a Randomized Clinical Trial.

BACKGROUND: Patients with stroke/transient ischemic attack and periodontal disease (PD) are at increased risk for cardiovascular events. PD treatments that can improve stroke risk factors were tested if they might assist patients with cerebrovascular disease. METHODS: In this multicenter phase II trial, patients with stroke/transient ischemic attack and moderately severe PD were randomly assigned to intensive or standard PD treatment arms. The primary outcome measure was a composite of death, myocardial infarction, and recurrent stroke, as well as adverse events. Secondary outcome included changes in stroke risk factors. RESULTS: A total of 1209 patients with stroke/transient ischemic attack were screened, of whom 481 met the PD eligibility criteria; 280 patients were randomized to intensive arm (n=140) and standard arm (n=140). In 12-month period, primary outcome occurred in 11 (8%) in the intensive arm and 17 (12%) in the standard arm. The intensive arm was nonsuperior to the standard arm (hazard ratio, 0.65 [95% CI, 0.30-1.38]) with similar rates of adverse events (sepsis 2.1% versus 0.7%; dental bleeding 1.4% versus 0%; and infective endocarditis 0.7% versus 0%). Secondary-outcome improvements were noted in both arms with diastolic blood pressure and high-density lipoprotein cholesterol (P<0.05). CONCLUSIONS: In patients with recent stroke/transient ischemic attack and PD, intensive PD treatment was not superior to standard PD treatment in prevention of stroke/myocardial infarction/death. Fewer events were noted in the intensive arm and the 2 arms were comparable in the safety outcomes. Secondary-outcome measures showed a trend toward improvement, with significant changes noted in diastolic blood pressure and high-density lipoprotein in both the treatment arms.

Re-Dosing del Nido cardioplegia in adult cardiac surgery: Perfusion characteristics and outcomes--Is there an optimal redosing strategy?

OBJECTIVES: del Nido cardioplegia is utilized for myocardial protection in adult patients undergoing cardiac surgery; however, no standardized re-dosing protocol exists. We describe perfusion characteristics and clinical outcomes in adult cardiac surgery patients who were re-dosed with del Nido cardioplegia. METHODS: Chart review was performed for adult patients undergoing cardiac surgery (specific inclusion/exclusion criteria below) who received exactly two doses of del Nido cardioplegia from 2012 to 2019; n = 542 patients. The main outcome was a composite endpoint comprised of operative mortality, myocardial infarction, post-operative cardiac support device (CSD), and postoperative decrease in ejection fraction (EF), which was analyzed via multivariable logistic regression (MVLR). A secondary analysis evaluated postoperative vasoactive-inotropic scores (VIS) via gamma log link regression (GLLR) as a more physiologic indication of myocardial recovery. RESULTS: MVLR demonstrated that increased total cardiopulmonary bypass (CPB) time was associated with a positive composite outcome (p < .001), whereas time between doses (p = .237) and the volume of each dose was not (p = .626). GLLR also demonstrated that prolonged CBP, decreased EF, congestive heart failure at time of surgery, and low hematocrit at the start of the surgery were all associated with higher VIS. CONCLUSIONS: In this retrospective study, variations in re-dosing strategy for del Nido cardioplegia do not affect postoperative outcomes and increased CPB time is associated with increased operative mortality, myocardial infarction, need for post-operative CSDs, and reduced postoperative EF, and increased VIS, irrespective of the re-dosing strategy. Further studies are warranted to to identify additional patient and operative characteristics that predispose to complications.

Care access and utilization among medicare beneficiaries living with Parkinson's disease.

An estimated 90% of people living with Parkinson's disease (PD) in the US are covered by Medicare health insurance. How these beneficiaries use and engage the health care system is important to understand in the face of a rapidly growing PD population. Here, we analyzed health care utilization patterns of those with a PD diagnosis enrolled in Medicare in 2019. By our estimates, PD beneficiaries number 685,116 or 1.2% of the total Medicare population. Compared to the overall Medicare population, 56.3% are male (vs 45.6%), 77.9% over age 70 (vs 57.1%), 14.7% people of color (vs 20.7%), and 16.0% are rural residents (vs 17.5%). Our analysis identified significant disparities in care. Surprisingly, 40% of PD beneficiaries (n = 274,046) did not see a neurologist at all during the calendar year and only 9.1% visited a movement disorder specialist (MDS). Few Medicare beneficiaries diagnosed with PD use recommended services such as physical, occupational, or speech therapy. People of color and rural residents were least likely to access a neurologist or therapy services. Despite 52.9% of beneficiaries being diagnosed with depression, only 1.8% had a clinical psychology visit. Our findings emphasize the need for further research on population-specific barriers to accessing PD-related health care.

Epigenome-wide association study using peripheral blood leukocytes identifies genomic regions associated with periodontal disease and edentulism in the Atherosclerosis Risk in Communities study.

AIM: To investigate individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood. MATERIALS AND METHODS: We included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at Visit 4 and had available data on DNA methylation from Visit 2 or 3. DNA methylation levels were compared by periodontal disease severity and edentulism through discovery analyses and subsequent testing of individual CpGs. RESULTS: Our discovery analysis replicated findings from a previous study reporting a region in gene ZFP57 (6p22.1) that was significantly hypomethylated in severe periodontal disease compared with no/mild periodontal disease in European American participants. Higher methylation levels in a separate region in an unknown gene (located in Chr10: 743,992-744,958) was associated with significantly higher odds of edentulism compared with no/mild periodontal disease in African American participants. In subsequent CpG testing, four CpGs in a region previously associated with periodontitis located within HOXA4 were significantly hypermethylated in severe periodontal disease compared with no/mild periodontal disease in African American participants (odds ratio per 1 SD increase in methylation level: cg11015251: 1.28 (1.02, 1.61); cg14359292: 1.24 (1.01, 1.54); cg07317062: 1.30 (1.05, 1.61); cg08657492: 1.25 (1.01, 1.55)). CONCLUSIONS: Our study highlights epigenetic variations in ZPF57 and HOXA4 that are significantly and reproducibly associated with periodontitis. Future studies should evaluate gene regulatory mechanisms in the candidate regions of these loci.

Factors Associated with Long-Term Prostate Cancer Survival after Palliative Radiotherapy to a Bone Metastasis and Contemporary Palliative Systemic Therapy: A Retrospective, Population-Based Study.

BACKGROUND: Radiation therapy (RT) is an established palliative treatment for bone metastases; however, little is known about post-radiation survival and factors which impact it. The aim of this study was to assess a population-based sample of metastatic prostate cancer patients receiving palliative radiation therapy to bone metastases and contemporary palliative systemic therapy and identify factors that impact long-term survival. MATERIALS/METHODS: This retrospective, population-based, cohort study assessed all prostate cancer patients receiving palliative RT for bone metastases at a Canadian provincial Cancer program during a contemporary time period. Baseline patient, disease, and treatment characteristics were extracted from the provincial medical physics databases and the electronic medical record. Post-RT Survival intervals were defined as the time interval from the first fraction of palliative RT to death from any cause or date of the last known follow-up. The median survival of the cohort was used to dichotomize the cohort into short- and long-term survivors following RT. Univariable and multivariable hazard regression analyses were performed to identify variables associated with post-RT survival. RESULTS: From 1 January 2018 until 31 December 2019, 545 palliative RT courses for bone metastases were delivered to n = 274 metastatic prostate cancer patients with a median age of 76 yrs (Interquartile range (IQR) 39-83) and a median follow-up of 10.6 months (range 0.2 to 47.9). The median survival of the cohort was 10.6 months (IQR 3.5-25 months). The ECOG performance status of the whole cohort was ≤2 in n = 200 (73%) and 3-4 in n = 67 (24.5%). The most commonly treated sites of bone metastasis were the pelvis and lower extremities n = 130 (47.4%), skull and spine n = 114 (41.6%), and chest and upper extremities n = 30 (10.9%). Most patients had CHAARTED high volume disease n = 239 (87.2%). On multivariable hazard regression analysis, an ECOG performance status of 3-4 (p = 0.02), CHAARTED high volume disease burden (p = 0.023), and non-receipt of systemic therapy (p = 0.006) were significantly associated with worse post-RT survival. CONCLUSION: Amongst metastatic prostate cancer patients treated with palliative radiotherapy to bone metastases and modern palliative systemic therapies, ECOG performance status, CHAARTED metastatic disease burden, and type of first-line palliative systemic therapy were significantly associated with post-RT survival durations.

Providing genetic testing and genetic counseling for Parkinson's disease to the community.

PURPOSE: To evaluate the feasibility and impact of offering genetic testing and counseling to patients with Parkinson's disease (PD), with the potential to enroll in gene-targeted clinical trials and improve clinical care. METHODS: A multicenter, exploratory pilot study at 7 academic hospital sites in the United States tracked enrollment and randomized participants to receive results and genetic counseling at local sites or by genetic counselors, remotely. Follow-up surveys measured participant/provider satisfaction, knowledge, and psychological impact. RESULTS: From September 5, 2019 to January 4, 2021, 620 participants were enrolled and 387 completed outcome surveys. There were no significant differences in outcomes between local and remote sites, with both arms reporting high knowledge and satisfaction scores (>80%). Notably, 16% of those tested had reportable PD gene variants (pathogenic/likely pathogenic/risk allele). CONCLUSION: Local clinicians, as well as genetic counselors, with educational support as needed, can effectively return genetic results for PD as we observed favorable outcome measures in both groups. Increasing access to PD genetic testing and counseling is urgent; this can inform future efforts to integrate genetic testing and counseling into clinical care for all those with PD.