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BackgroundThe penetrance of common genetic risk variants for Parkinson's disease (PD) is low. Pesticide exposure increases PD risk, but how exposure affects penetrance is not well understood.ObjectiveTo determine the relationship between occupational pesticide exposure and PD in people with LRRK2 and GBA risk variants.MethodsParticipants of the Parkinson's Progression Markers Initiative (PPMI) with a LRRK2-G2019 S or GBA risk variant provided information about occupational pesticide exposure. We compared exposure in carriers with and without PD. Among carriers with PD, we used Cox proportional hazard models to compare time-to impairment in balance, cognition, and activities of daily living (ADLs) between participants with and without prior occupational pesticide exposure.Results378 participants with a risk variant provided exposure information; 176 with LRRK2-G2019 S (54 with and 122 without PD) and 202 with GBA variants (47 with and 155 without PD). Twenty-six participants reported pesticide exposure. People with a GBA variant and occupational pesticide exposure had much higher odds of PD (aOR: 5.4, 95% CI 1.7-18.5, p

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia.

IntroductionEarly diagnosis of Parkinson's disease (PD) is important to identify treatments to slow neurodegeneration. People who develop PD often have symptoms before the disease manifests and may be coded as diagnoses in the electronic health record (EHR).MethodsTo predict PD diagnosis, we embedded EHR data of patients onto a biomedical knowledge graph called Scalable Precision medicine Open Knowledge Engine (SPOKE) and created patient embedding vectors. We trained and validated a classifier using these vectors from 3,004 PD patients, restricting records to 1, 3, and 5 years before diagnosis, and 457,197 non-PD group.ResultsThe classifier predicted PD diagnosis with moderate accuracy (AUC = 0.77 ± 0.06, 0.74 ± 0.05, 0.72 ± 0.05 at 1, 3, and 5 years) and performed better than other benchmark methods. Nodes in the SPOKE graph, among cases, revealed novel associations, while SPOKE patient vectors revealed the basis for individual risk classification.DiscussionThe proposed method was able to explain the clinical predictions using the knowledge graph, thereby making the predictions clinically interpretable. Through enriching EHR data with biomedical associations, SPOKE may be a cost-efficient and personalized way to predict PD diagnosis years before its occurrence.

The etiologies of Parkinson's disease (PD) remain unclear. Some, such as certain genetic mutations and head trauma, are widely known or easily identified. However, these causes or risk factors do not account for the majority of cases. Other, less visible factors must be at play. Among these is a widely used industrial solvent and common environmental contaminant little recognized for its likely role in PD: trichloroethylene (TCE). TCE is a simple, six-atom molecule that can decaffeinate coffee, degrease metal parts, and dry clean clothes. The colorless chemical was first linked to parkinsonism in 1969. Since then, four case studies involving eight individuals have linked occupational exposure to TCE to PD. In addition, a small epidemiological study found that occupational or hobby exposure to the solvent was associated with a 500% increased risk of developing PD. In multiple animal studies, the chemical reproduces the pathological features of PD.Exposure is not confined to those who work with the chemical. TCE pollutes outdoor air, taints groundwater, and contaminates indoor air. The molecule, like radon, evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected. Despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited. Here, through a literature review and seven illustrative cases, we postulate that this ubiquitous chemical is contributing to the global rise of PD and that TCE is one of its invisible and highly preventable causes. Further research is now necessary to examine this hypothesis.

Virtual reality (VR) is an increasingly available resource with numerous applications to medical education, and as a teaching tool has been widely validated in the literature. Photogrammetry, the process of overlapping two-dimensional (2D) photographic images of three-dimensional (3D) objects to create a 3D image or "model," can be used in conjunction with VR to create pedagogically sound learning modules for anatomy education. However, to date, there has not been a detailed description of the process of developing and implementing an in-house VR tool to supplement anatomy instruction. In this article, we examine the methods, benefits, and challenges of using photogrammetry to implement a VR classroom that capitalizes on the strengths of a traditional body donor-based course and the unique strengths of VR. Using off-the-shelf equipment, developing VR content and a VR curriculum is both feasible and approachable for medical educators.

BackgroundParkinson's disease (PD) is a chronic, disabling neurodegenerative disorder.ObjectiveTo predict a future diagnosis of PD using questionnaires and simple non-invasive clinical tests.MethodsParticipants in the prospective Kuakini Honolulu-Asia Aging Study (HAAS) were evaluated biannually between 1995-2017 by PD experts using standard diagnostic criteria. Autopsies were sought on all deaths. We input simple clinical and risk factor variables into an ensemble-tree based machine learning algorithm and derived models to predict the probability of developing PD. We also investigated relationships of predictive models and neuropathologic features such as nigral neuron density.ResultsThe study sample included 292 subjects, 25 of whom developed PD within 3 years and 41 by 5 years. 116 (46%) of 251 subjects not diagnosed with PD underwent autopsy. Light Gradient Boosting Machine modeling of 12 predictors correctly classified a high proportion of individuals who developed PD within 3 years (area under the curve (AUC) 0.82, 95%CI 0.76-0.89) or 5 years (AUC 0.77, 95%CI 0.71-0.84). A large proportion of controls who were misclassified as PD had Lewy pathology at autopsy, including 79%of those who died within 3 years. PD probability estimates correlated inversely with nigral neuron density and were strongest in autopsies conducted within 3 years of index date (r = -0.57, p

The Trial of Parkinson's And Zoledronic acid (TOPAZ, https://clinicaltrials.gov/ct2/show/NCT03924414 ) is a unique collaboration between experts in movement disorders and osteoporosis to test the efficacy of zoledronic acid, an FDA-approved parenteral treatment for osteoporosis, for fracture prevention in people with neurodegenerative parkinsonism. Aiming to enroll 3,500 participants age 65 years or older, TOPAZ is one of the largest randomized, placebo-controlled clinical trials ever attempted in parkinsonism. The feasibility of TOPAZ is enhanced by its design as a U.S.- wide home-based trial without geographical limits. Participants receive information from multiple sources, including specialty practices, support groups and websites. Conducting TOPAZ in participants' homes takes advantage of online consent technology, the capacity to confirm diagnosis using telemedicine and the availability of research nursing to provide screening and parenteral therapy in homes. Home-based clinical research may provide an efficient, convenient, less expensive method that opens participation in clinical trials to almost anyone with parkinsonism.

The gastrointestinal microbiome is altered in Parkinson's disease and likely plays a key role in its pathophysiology, affecting symptoms and response to therapy and perhaps modifying progression or even disease initiation. Gut dysbiosis therefore has a significant potential as a therapeutic target in Parkinson's disease, a condition elusive to disease-modifying therapy thus far. The gastrointestinal environment hosts a complex ecology, and efforts to modulate the relative abundance or function of established microorganisms are still in their infancy. Still, these techniques are being rapidly developed and have important implications for our understanding of Parkinson's disease. Currently, modulation of the microbiome can be achieved through non-pharmacologic means such as diet, pharmacologically through probiotic, prebiotic, or antibiotic use and procedurally through fecal transplant. Novel techniques being explored include the use of small molecules or genetically engineered organisms, with vast potential. Here, we review how some of these approaches have been used to date, important areas of ongoing research, and how microbiome modulation may play a role in the clinical management of Parkinson's disease in the future.

BackgroundThe penetrance of leucine rich repeat kinase 2 (LRRK2) mutations is incomplete and may be influenced by environmental and/or other genetic factors. Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to reduce inflammation and may lower Parkinson's disease (PD) risk, but their role in LRRK2-associated PD is unknown.ObjectivesThe objective of this study is to evaluate the association of regular NSAID use and LRRK2-associated PD.MethodsSymptomatic ("LRRK2-PD") and asymptomatic ("LRRK2-non-PD") participants with LRRK2 G2019S, R1441X, or I2020T variants (definitely pathogenic variant carriers) or G2385R or R1628P variants (risk variant carriers) from 2 international cohorts provided information on regular ibuprofen and/or aspirin use (≥2 pills/week for ≥6 months) prior to the index date (diagnosis date for PD, interview date for non-PD). Multivariate logistic regression was used to evaluate the relationship between regular NSAID use and PD for any NSAID, separately for ibuprofen and aspirin in all carriers and separately in pathogenic and risk variant groups.ResultsA total of 259 LRRK2-PD and 318 LRRK2-non-PD participants were enrolled. Regular NSAID use was associated with reduced odds of PD in the overall cohort (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.21-0.57) and in both pathogenic and risk variant carriers (ORPathogenic , 0.38; 95% CI, 0.21-0.67 and ORRiskVariant , 0.19; 95% CI, 0.04-0.99). Similar associations were observed for ibuprofen and aspirin separately (ORIbuprofen , 0.19; 95% CI, 0.07-0.50 and ORAspirin , 0.51; 95% CI, 0.28-0.91).ConclusionsRegular NSAID use may be associated with reduced penetrance in LRRK2-associated PD. The LRRK2 protein is involved in inflammatory pathways and appears to be modulated by regular anti-inflammatory use. Longitudinal observational and interventional studies of NSAID exposure and LRRK2-PD are needed to confirm this association. © 2020 International Parkinson and Movement Disorder Society.

Autonomic nervous system involvement precedes the motor features of Parkinson's disease (PD). Our goal was to develop a proof-of-concept model for identifying subjects at high risk of developing PD by analysis of cardiac electrical activity. We used standard 10-s electrocardiogram (ECG) recordings of 60 subjects from the Honolulu Asia Aging Study including 10 with prevalent PD, 25 with prodromal PD, and 25 controls who never developed PD. Various methods were implemented to extract features from ECGs including simple heart rate variability (HRV) metrics, commonly used signal processing methods, and a Probabilistic Symbolic Pattern Recognition (PSPR) method. Extracted features were analyzed via stepwise logistic regression to distinguish between prodromal cases and controls. Stepwise logistic regression selected four features from PSPR as predictors of PD. The final regression model built on the entire dataset provided an area under receiver operating characteristics curve (AUC) with 95% confidence interval of 0.90 [0.80, 0.99]. The five-fold cross-validation process produced an average AUC of 0.835 [0.831, 0.839]. We conclude that cardiac electrical activity provides important information about the likelihood of future PD not captured by classical HRV metrics. Machine learning applied to ECGs may help identify subjects at high risk of having prodromal PD.

Coronavirus disease-2019 (COVID-19) disrupted the in-person teaching format of anatomy. To study changes in gross anatomy education that occurred during August--December, 2020 compared to before the pandemic, an online survey was distributed to anatomy educators. The 191 responses received were analyzed in total and by academic program, geographic region, and institution type. Cadaver use decreased overall (before: 74.1 ± 34.1%, during: 50.3 ± 43.0%, P < 0.0001), as well as across allopathic and osteopathic medicine, therapy, undergraduate, and veterinary programs (P < 0.05), but remained unchanged for other programs (P > 0.05). Cadaver use decreased internationally and in the US (P < 0.0001), at public and private (P < 0.0001) institutions, and among allopathic medical programs in Northeastern, Central, and Southern (P < 0.05), but not Western, US geographical regions. Laboratories during Covid-19 were delivered through synchronous (59%), asynchronous (4%), or mixed (37%) formats (P < 0.0001) and utilized digital resources (47%), dissection (32%), and/or prosection (21%) (P < 0.0001). The practical laboratory examination persisted during COVID-19 (P = 0.419); however, the setting and materials shifted to computer-based (P < 0.0001) and image-based (P < 0.0001), respectively. In-person lecture decreased during COVID-19 (before: 88%, during: 24%, P = 0.003). When anatomy digital resources were categorized, dissection media, interactive software, and open-access content increased (P [less than or equal to] 0.008), with specific increases in BlueLink, Acland's Videos, and Complete Anatomy (P < 0.05). This study provided evidence of how gross anatomy educators continued to adapt their courses past the early stages of the pandemic.

BackgroundThe effect of the COVID-19 pandemic on people with Parkinson's disease (PD) is poorly understood.ObjectiveTo rapidly identify areas of need and improve care in people with PD during the COVID-19 pandemic, we deployed a survey to assess COVID-19 symptoms and the pandemic's effect among those with and without COVID-19.MethodsPeople with and without PD participating in the online study Fox Insight (FI) were invited to complete a survey between April 23 and May 23, 2020. Among people reporting COVID-19 diagnoses, we compared symptoms and outcomes in people with and without PD. Among people not reporting COVID-19, we assessed access to healthcare and services and PD symptoms.Results7,209/9,762 active FI users responded (approximately 74% response rate), 5,429 people with PD and 1,452 without PD. COVID-19 diagnoses were reported by 51 people with and 26 without PD. Complications were more frequent in people with longer PD duration. People with PD and COVID-19 experienced new or worsening motor (63%) and nonmotor (75%) symptoms. People with PD not diagnosed with COVID-19 reported disrupted medical care (64%), exercise (21%), and social activities (57%), and worsened motor (43%) and non-motor (52%) symptoms. Disruptions were more common for those living alone, with lower income and non-White race.ConclusionsThe COVID-19 pandemic is associated with wide-ranging effects on people with PD, and certain groups may be at particular risk. FI provides a rapid, patient-centered means to assess these effects and identify needs that can be used to improve the health of people with PD.

PurposeCardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation.MethodsShort-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls.ResultsBeat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls.ConclusionsIncreased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD.

BackgroundA carbohydrate-restricted (CR) diet can improve glycemic control in people with type 2 diabetes mellitus (T2DM). There are concerns, however, that the high dietary fat content of CR diets can increase low-density lipoprotein cholesterol (LDL-C), thus increasing cardiovascular disease (CVD) risk. Quantifying CVD risk associated with changes in LDL-C in the context of CR diets is complicated by the fact that LDL-C reflects heterogeneous lipids. For example, small LDL particle number (sLDL-P) is more closely associated with CVD risk than is total LDL-C, and CR diets tend to decrease the proportion of sLDL-C in LDL-C, which standard lipid measures do not indicate. Advanced lipoprotein assays, such as nuclear magnetic resonance (NMR) testing, can subfractionate lipoproteins by size and density and may better depict the effects of CR diets on CVD risk.MethodsAdults (N = 58) with T2DM (n = 37 women; baseline HbA1c ≥ 6.5%) completed a 6-month group-based CR diet intervention. We obtained a standard lipid panel, advanced lipoprotein assays (NMR testing), and two 24-h diet recalls at baseline and post-intervention (6 months). Participants also completed home-based blood ketone testing (a biological index of dietary adherence) during the final five weeks of the intervention.ResultsFrom baseline to post-intervention, participants had increased mean HDL-C, decreased triglycerides and triglyceride/HDL ratio, decreased mean sLDL-P, and increased LDL size, which reflect reductions in CVD risk (ps

The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the USA. It comprises 15,924 White male twin pairs born in the years 1917-1927 (N = 31.848), both of whom served in the armed forces, chiefly during World War II. This article updates activities in this registry since the most recent report in Twin Research and Human Genetics (Page, 2006). Records-based data include information from enlistment charts and Veterans Administration data linkages. There have been three major epidemiologic questionnaires and an education and earnings survey. Separate data collection efforts with the NAS-NRC registry include the National Heart, Lung, and Blood Institute (NHLBI) subsample, the Duke Twins Study of Memory in Aging and a clinically based study of Parkinson's disease. Progress has been made on consolidating the various data holdings of the NAS-NRC Twin Registry. Data that had been available through the National Academy of Sciences are now freely available through National Archive of Computerized Data on Aging (NACDA).

Cadherins constitute a family of transmembrane proteins that mediate calcium-dependent cell-cell adhesion. The extracellular domain of cadherins consists of extracellular cadherin (EC) domains, separated by calcium binding sites. The EC interacts with other cadherin molecules in cis and in trans to mechanically hold apposing cell surfaces together. CDH2 encodes N-cadherin, whose essential roles in neural development include neuronal migration and axon pathfinding. However, CDH2 has not yet been linked to a Mendelian neurodevelopmental disorder. Here, we report de novo heterozygous pathogenic variants (seven missense, two frameshift) in CDH2 in nine individuals with a syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, variable axon pathfinding defects (corpus callosum agenesis or hypoplasia, mirror movements, Duane anomaly), and ocular, cardiac, and genital anomalies. All seven missense variants (c.1057G>A [p.Asp353Asn]; c.1789G>A [p.Asp597Asn]; c.1789G>T [p.Asp597Tyr]; c.1802A>C [p.Asn601Thr]; c.1839C>G [p.Cys613Trp]; c.1880A>G [p.Asp627Gly]; c.2027A>G [p.Tyr676Cys]) result in substitution of highly conserved residues, and six of seven cluster within EC domains 4 and 5. Four of the substitutions affect the calcium-binding site in the EC4-EC5 interdomain. We show that cells expressing these variants in the EC4-EC5 domains have a defect in cell-cell adhesion; this defect includes impaired binding in trans with N-cadherin-WT expressed on apposing cells. The two frameshift variants (c.2563_2564delCT [p.Leu855Valfs∗4]; c.2564_2567dupTGTT [p.Leu856Phefs∗5]) are predicted to lead to a truncated cytoplasmic domain. Our study demonstrates that de novo heterozygous variants in CDH2 impair the adhesive activity of N-cadherin, resulting in a multisystemic developmental disorder, that could be named ACOG syndrome (agenesis of corpus callosum, axon pathfinding, cardiac, ocular, and genital defects).

Encoding the slow skeletal muscle isoform of myosin binding protein-C, MYBPC1 is associated with autosomal dominant and recessive forms of arthrogryposis. The authors describe a novel association for MYBPC1 in four patients from three independent families with skeletal muscle weakness, myogenic tremors, and hypotonia with gradual clinical improvement. The patients carried one of two de novo heterozygous variants in MYBPC1, with the p.Leu263Arg variant seen in three individuals and the p.Leu259Pro variant in one individual. Both variants are absent from controls, well conserved across vertebrate species, predicted to be damaging, and located in the M-motif. Protein modeling studies suggested that the p.Leu263Arg variant affects the stability of the M-motif, whereas the p.Leu259Pro variant alters its structure. In vitro biochemical and kinetic studies demonstrated that the p.Leu263Arg variant results in decreased binding of the M-motif to myosin, which likely impairs the formation of actomyosin cross-bridges during muscle contraction. Collectively, our data substantiate that damaging variants in MYBPC1 are associated with a new form of an early-onset myopathy with tremor, which is a defining and consistent characteristic in all affected individuals, with no contractures. Recognition of this expanded myopathic phenotype can enable identification of individuals with MYBPC1 variants without arthrogryposis.

BackgroundFamily screening of a 48-year-old male with recently diagnosed IgG4-related disease (IgG4-RD) revealed unanticipated elevations in plasma IgG4 in his two healthy teenaged sons.MethodsWe performed gene sequencing, immune cell studies, HLA typing, and analyses of circulating cytotoxic CD4+ T lymphocytes and plasmablasts to seek clues to pathogenesis. DNA from a separate cohort of 99 patients with known IgG4-RD was also sequenced for the presence of genetic variants in a specific gene, FGFBP2.ResultsThe three share a previously unreported heterozygous single base deletion in fibroblast growth factor binding protein type 2 (FGFBP2), which causes a frameshift in the coding sequence. The FGFBP2 protein is secreted by cytotoxic T-lymphocytes and binds fibroblast growth factor. The variant sequence in the FGFBP2 protein is predicted to form a disordered random coil rather than a helical-turn-helix structure, unable to adopt a stable conformation. The proband and the two sons had 5-10-fold higher numbers of circulating cytotoxic CD4 + T cells and plasmablasts compared to matched controls. The three members also share a homozygous missense common variant in FGFBP2 found in heterozygous form in ~40% of the population. This common variant was found in 73% of an independent, well characterized IgG4-RD cohort, showing enrichment in idiopathic IgG4-RD.ConclusionsThe presence of a shared deleterious variant and homozygous common variant in FGFBP2 in the proband and sons strongly implicates this cytotoxic T cell product in the pathophysiology of IgG4-RD. The high prevalence of a common FGFBP2 variant in sporadic IgG4-RD supports the likelihood of participation in disease.

Purpose: To investigate the impact of direct aortic cannulation (DAC) versus femoral arterial cannulation (FAC) on clinical outcomes of surgery for acute type A aortic dissection. Methods: PubMed/MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched until August 25, 2023, to conduct a meta-analysis. Primary endpoints of the study were operative mortality and postoperative stroke. Secondary endpoints were cardiopulmonary bypass time, myocardial ischemic time, hypothermic circulatory arrest time, temporary neurological dysfunction (TND), combined stroke and TND, re-exploration for bleeding, and need for renal replacement therapy. A random-effect model was used to estimate the pooled effect size, and a leave-one-out method was used for the primary endpoints for sensitivity analysis. Results: 15 studies met our eligibility criteria, including a total of 7941 samples. Operative mortality was significantly lower in the DAC group with a pooled odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.61–0.85)]. Incidence of postoperative stroke was also lower in the DAC group with a pooled OR of 0.79 (95% CI: 0.66–0.94). However, after excluding one study with the greatest weight, the difference became nonsignificant. DAC was also associated with a lower incidence of postoperative TND, and re-exploration for bleeding with a pooled OR of 0.52 (95% CI: 0.37–0.73), and 0.60 (95% CI: 0.47–0.77), respectively. Conclusions: This meta-analysis showed that patients who underwent ATAAD repair with DAC had a lower incidence of operative mortality, postoperative stroke, TND, and re-exploration for bleeding compared to those who underwent FAC. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have become the mainstay treatment of metastatic kidney cancer, demonstrating enhanced outcomes and durable responses in select patient subgroups. However, identifying reliable prognostic biomarkers for treatment outcomes remains challenging. Objectives: This study aimed to assess the correlation between baseline inflammatory markers and overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) in metastatic kidney cancer patients receiving ICIs. CB was defined as patients achieving stable disease, partial response, or complete response. Design: Retrospective, single-center study. Methods: A retrospective analysis was conducted on 401 adult patients with advanced kidney cancer treated with ICIs at Emory Winship Cancer Institute between 2018 and 2023. Modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and neutrophil-to-eosinophil ratios (NER) were collected from baseline blood samples. Results: Among 401 patients (median age, 66; 71% male; 21% Black/African American), median follow-up was 43.0 months (95% CI, 36.6–51.4). Patients with mGPS scores of 0 had longer OS than those with a score of 1 (hazard ratio (HR), 0.38; 95% CI, 0.23–0.62; p < 0.001) and 2 (HR, 0.37; 95% CI, 0.20–0.67; p = 0.001), and longer PFS compared to patients with mGPS scores of 1 (HR, 0.66; 95% CI, 0.44–0.98; p = 0.039) and 2 (HR, 0.44; 95% CI, 0.29–0.67; p < 0.001). Low baseline NLR was associated with longer PFS (HR, 0.73; 95% CI, 0.54–0.97; p = 0.032). Low baseline MLR correlated with improved OS (HR, 0.60; 95% CI, 0.44–0.83; p = 0.002) and PFS (HR, 0.73; 95% CI, 0.55–0.97; p = 0.031). Similarly, low baseline PLR was associated with higher CB likelihood (odds ratio (OR), 2.20; 95% CI, 1.31–3.69; p = 0.003), and low baseline NER was linked to improved OS (HR, 0.63; 95% CI, 0.46–0.87; p = 0.004), PFS (HR, 0.67; 95% CI, 0.51–0.88; p = 0.003), and higher CB (OR, 2.04; 95% CI, 1.20–3.46; p = 0.008). Conclusion: Lower levels of systemic inflammatory markers are associated with more favorable clinical outcomes with ICI treatment. Prospective studies are needed for further validation. [ABSTRACT FROM AUTHOR]

Plant-based diets are associated with numerous health benefits, including reduced risks of chronic diseases. However, questions persist regarding the implications of lower dietary intakes of certain non-essential nutrients, such as retinol, vitamin K2, carnitine, and creatine, which are primarily found in animal-derived foods. This narrative review evaluates the roles of these nutrients in human physiology and examines whether their absence in plant-based diets is likely to impact health outcomes. Retinol requirements can be met through the consumption of provitamin A carotenoids in plant foods, even in individuals with reduced conversion efficiency. Endogenous synthesis adequately supports physiological needs for vitamin K2, and currently available evidence does not consistently demonstrate that dietary vitamin K2 provides additional benefits for bone or cardiovascular health. Carnitine and creatine levels may differ between individuals following omnivorous and plant-based diets, but these differences do not result in compromised muscle function, cognitive health, or metabolic outcomes. Current evidence does not indicate that the absence of these non-essential nutrients in plant-based diets adversely affects health or confers disadvantages compared to omnivorous diets. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) created unparalleled challenges to anatomy education. Gross anatomy education has been particularly impacted given the traditional in-person format of didactic instruction and/or laboratory component(s). To assess the changes in gross anatomy lecture and laboratory instruction, assessment, and teaching resources utilized as a result of COVID-19, a survey was distributed to gross anatomy educators through professional associations and listservs. Of the 67 survey responses received for the May-August 2020 academic period, 84% were from United States (US) institutions, while 16% were internationally based. Respondents indicated that in-person lecture decreased during COVID-19 (before: 76%, during: 8%, P < 0.001) and use of cadaver materials declined (before: 76 ± 33%, during: 34 ± 43%, P < 0.001). The use of cadaver materials in laboratories decreased during Covid-19 across academic programs, stand-alone and integrated anatomy courses, and private and public institutions (P [less than or equal to] 0.004). Before COVID-19, cadaveric materials used in laboratories were greater among professional health programs relative to medical and undergraduate programs (P [less than or equal to] 0.03) and among stand-alone relative to integrated anatomy courses (P [less than or equal to] 0.03). Furthermore, computer-based assessment increased (P < 0.001) and assessment materials changed from cadaveric material to images (P < 0.03) during COVID-19, even though assessment structure was not different (P > 0.05). The use of digital teaching resources increased during COVID-19 (P < 0.001), with reports of increased use of in-house created content, BlueLink, and Complete Anatomy software (P < 0.05). While primarily representing US institutions, this study provided evidence of how anatomy educators adapted their courses, largely through virtual mediums, and modified laboratory protocols during the initial emergence of the COVID-19 pandemic.