Systematic review. The study's primary objective was to determine how osteobiologic choice affects fusion rates in patients undergoing anterior cervical discectomy and fusion (ACDF). The study's secondary objectives were to 1) determine the optimal timing of fusion assessment following ACDF and 2) determine if osteobiologic type affects the timing and optimal modality of fusion assessment. A systematic search of PubMed/MEDLINE was conducted for literature published from 2000 through October 2020 comparing anterior fusion in the cervical spine with various osteobiologics. Both comparative studies and case series of ≥10 patients were included. A total of 74 studies met the inclusion criteria. Seventeen studies evaluated the efficacy of autograft on fusion outcomes, and 23 studies assessed the efficacy of allograft on fusion outcomes. 3 studies evaluated the efficacy of demineralized bone matrix, and seven assessed the efficacy of rhBMP-2 on fusion outcomes. Other limited studies evaluated the efficacy of ceramics and bioactive glasses on fusion outcomes, and 4 assessed the efficacy of stem cell products. Most studies utilized dynamic radiographs for the assessment of fusion. Overall, there was a general lack of supportive data to determine the optimal timing of fusion assessment meaningfully or if osteobiologic type influenced fusion timing. Achieving fusion following ACDF appears to remain an intricate interplay between host biology and various surgical factors, including the selection of osteobiologics. While alternative osteobiologics to autograft exist and may produce acceptable fusion rates, limitations in study methodology prevent any definitive conclusions from existing literature.

Converging lines of evidence suggest that microglia are relevant to Parkinson's disease pathogenesis, justifying exploration of therapeutic agents thought to attenuate pathogenic microglial function. We sought to test the safety and efficacy of NLY01-a brain-penetrant, pegylated, longer-lasting version of exenatide (a glucagon-like peptide-1 receptor agonist) that is believed to be anti-inflammatory via reduction of microglia activation-in Parkinson's disease. We report a 36-week, randomised, double-blind, placebo-controlled study of NLY01 in participants with early untreated Parkinson's disease conducted at 58 movement disorder clinics in the USA. Participants meeting UK Brain Bank or Movement Disorder Society research criteria for Parkinson's disease were randomly allocated (1:1:1) to one of two active treatment groups (2·5 mg or 5·0 mg NLY01) or matching placebo, based on a central computer-generated randomisation scheme using permuted block randomisation with varying block sizes. All participants, investigators, coordinators, study staff, and sponsor personnel were masked to treatment assignments throughout the study. The primary efficacy endpoint for the primary analysis population (defined as all randomly assigned participants who received at least one dose of study drug) was change from baseline to week 36 in the sum of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts II and III. Safety was assessed in the safety population (all randomly allocated participants who received at least one dose of the study drug) with documentation of adverse events, vital signs, electrocardiograms, clinical laboratory assessments, physical examination, and scales for suicidality, sleepiness, impulsivity, and depression. This trial is complete and registered at ClinicalTrials.gov, NCT04154072. The study took place between Jan 28, 2020, and Feb 16, 2023. 447 individuals were screened, of whom 255 eligible participants were randomly assigned (85 to each study group). One patient assigned to placebo did not receive study treatment and was not included in the primary analysis. At 36 weeks, 2·5 mg and 5·0 mg NLY01 did not differ from placebo with respect to change in sum scores on MDS-UPDRS parts II and III: difference versus placebo -0·39 (95% CI -2·96 to 2·18; p=0·77) for 2·5 mg and 0·36 (-2·28 to 3·00; p=0·79) for 5·0 mg. Treatment-emergent adverse events were similar across groups (reported in 71 [84%] of 85 patients on 2·5 mg NLY01, 79 [93%] of 85 on 5·0 mg, and 73 [87%] of 84 on placebo), with gastrointestinal disorders the most commonly observed class in active groups (52 [61%] for 2·5 mg, 64 [75%] for 5·0 mg, and 30 [36%] for placebo) and nausea the most common event overall (33 [39%] for 2·5 mg, 49 [58%] for 5·0 mg, and 16 [19%] for placebo). No deaths occurred during the study. NLY01 at 2·5 and 5·0 mg was not associated with any improvement in Parkinson's disease motor or non-motor features compared with placebo. A subgroup analysis raised the possibility of motor benefit in younger participants. Further study is needed to determine whether these exploratory observations are replicable. D&D Pharmatech-Neuraly.

Alzheimer's disease(AD) is being the burden of society and family. Applying computing-aided strategies to reveal its pathology is one of the research highlights. Plasma neurofilament light (NFL) is an emerging noninvasive and economic biomarker for AD molecular pathology. It is valuable to reveal the correlations between the plasma NFL levels and neurodegeneration, especially hippcampal deformations at the preclinical stage. The negative correlation between plasma NFL levels and hippocampal volumes has been documented. However, the relationship between the plasma NFL levels and the hippocampal morphometry details at the preclinical stage is still elusive. This study seeks to demonstrate the capacity of our proposed surface-based hippocampal morphometry system to discern the plasma NFL positive (NFL+>41.9 pg/L) level and plasma NFL negative (NFL-<41.9pg/L) level and illustrate its superiority to the hippocampal volume measurement by drawing the cohort of 154 CU middle aged and elderly adults. We also apply this morphometry measure and a proposed sparse coding based classification algorithm to classify CU individuals with NFL+ and NFL- levels. Experimental results show that the proposed hippocampal morphometry system offers stronger statistical power to discriminate CU subjects with NFL+ and NFL- levels, comparing with the hippocampal volume measure. Furthermore, this system can discriminate plasma NFL levels in CU individuals (Accuracy=0.86). Both the group level and individual level analysis results indicate that the association between plasma NFL levels and the hippocampal shapes can be mapped at the preclinical stage.

Background: Warfarin remains the anticoagulant of choice for patients with antiphospholipid syndrome (APLS). However, conflicting data exists regarding the role of direct oral anticoagulants (DOACs) as reasonable alternatives to warfarin, which has a less desirable side effect profile. In clinical practice, some patients start taking DOACs or aspirin before an official APLS diagnosis is confirmed and these patients may choose to continue a DOAC after an informed discussion with their hematologist. To gain a better understanding of anticoagulant use in APLS at our center, we conducted a retrospective study to assess the clinical characteristics of patients diagnosed with APLS. Methods: All patients with an ICD-10 code indicating APLS from January of 2020 to April of 2023 were included. Patient characteristics, relevant laboratory testing (lupus anticoagulant, beta-2 glycoprotein IgG/IgM, and anti-cardiolipin IgG/IgM), and treatment history were extracted from the electronic medical record. Patients were deemed to have single positivity if any one of the following were present: detectable lupus anticoagulant, elevated (defined as &amp;gt;40 GPL) beta-2 glycoprotein (B2GP) IgG or IgM, or elevated cardiolipin IgG or IgM both on initial and confirmatory testing (performed approximately 12 weeks later). Similarly, double positivity was defined as the presence of two of these biomarkers and triple positive was defined as the presence of three of these biomarkers. Initial laboratory testing results are included in Table 1. Statistical analysis was conducted using the SAS software (SAS Enterprise Guide 7.1) and the R Core Team (R 4.2.2). Continuous variables such as BMI and age were evaluated using the Wilcoxon rank-sum test, while categorical variables were assessed using Fisher's Exact Test and Chi-squared test. Results: Seventy-two patients were included in our analysis. Mean age and BMI were 56.3 ± 16.8 years and 32.3 ± 11.2, respectively. The majority of patients were female (69.4%) and white (83.8%). Approximately half of all patients had single positivity (64.4%) and more than half had detectable lupus anticoagulant (58.7%). Cardiolipin IgM was the most frequently (36.1%) elevated biomarker. Patient characteristics between the DOAC/aspirin and warfarin/enoxaparin cohorts were not significantly different; however, significantly more patients with single positivity received DOAC/Aspirin rather than warfarin/enoxaparin (77.8% vs.43.5%, p = 0.012). There was no statistically significant difference between the frequency of arterial complications in patients who took DOAC/Aspirin (4 events in 39 patients) versus those who took warfarin/enoxaparin (1 event in 33 patients), p = 0.366. The majority of arterial complications (4 of 5 events) occurred in patients with double and triple positivity. In addition, a logistical regression was performed regarding different characteristic effects on positivity level (single, double or triple laboratory positive), which found the presence of lupus anticoagulant had a significant association with higher likelihood of double/triple positivity (p = 0.048). Conclusion: This study provides potential reassurance for clinicians regarding the use of DOACs during the investigative phase of APLS and supports the continuation of DOAC therapy in patients, particularly those with single positivity, after careful evaluation and shared decision-making with patients. However, caution should be kept when considering DOAC use in patients with lupus anticoagulant, double, or triple positivity, due to concerning arterial events. Further large multi-center randomized clinical trials are necessary in the future to clarify the role of DOACs in APLS.

BACKGROUND Prehospital identification of large‐vessel occlusion (LVO) stroke facilitates the development of a regional triage protocol that could lead to an improvement in intrahospital and interhospital workflows. This requires stroke education of emergency medical services (EMS) personnel to improve stroke recognition, severity assessment, and prenotification. However, the current state of EMS personnel's knowledge of LVO stroke, their training for stroke severity assessment, and their preferences for educational methods are unknown. We conducted a nationwide EMS survey across the United States to glean insights that can inform and customize future EMS educational efforts. METHODS The Society of Vascular and Interventional Neurology, in collaboration with EMS World , created an online questionnaire for EMS personnel. It included 12 multiple‐choice and free‐response questions designed to test participants’ clinical knowledge of LVO, knowledge of stroke center certification levels, prior LVO educational experiences, preferences for educational content delivery, and perspectives on prehospital hurdles to stroke care. All subscribers of EMS World received a survey link via email. RESULTS Of the 38 486 subscribers of EMS World , the survey email was opened by 1830, of whom 1107 completed the survey across all states in the United States, with a response rate of 2.9%. Most of the respondents identified themselves as paramedics/emergency medical technicians (91%). The number of patients with stroke that survey participants transported in the past year was &lt;10 for 618 (56%). Only 285 (26%) participants answered both LVO knowledge questions correctly, and only 128 (12%) respondents correctly identified all types of stroke centers with thrombectomy capability. A total of 362 EMS personnel (33%) denied receiving training to perform LVO severity assessment. Respondents who received training to perform an LVO scale demonstrated nearly twice the prevalence of LVO knowledge (30.6% versus 15.7%; prevalence ratio, 1.94 [95% CI, 1.50–2.53]) than respondents who did not receive training. The top hurdle to prehospital LVO education was identified as the lack of standardized LVO training by 535 (48%) respondents. CONCLUSIONS EMS providers in the United States reported inadequate LVO training and demonstrated gaps in knowledge of LVO, stroke severity scales, and stroke center levels. Systematic efforts to enhance and standardize the educational content and delivery of LVO education are needed.

BackgroundRP1 is an HSV-1-based oncolytic immunotherapy expressing GM-CSF and the fusogenic GALV-GP-R- protein. We present biodistribution and shedding data from 87 patients enrolled in the phase 1 dose expansion (n=14) and phase 2 (n=73) cohorts from the ongoing IGNYTE clinical trial (NCT03767348).MethodsPatients received RP1 via intratumoral injection into superficial or deep, including visceral, lesions. Nivolumab was given at 240mg Q2W for 4 months, then 480mg Q4W for 20 months from the second dose of RP1. Blood, urine, oral mucosa/saliva, swab samples, and injection-site dressings were collected at various timepoints on the study. Samples were assessed for the presence of RP1 DNA by an RP1-specific qPCR assay; any swab samples positive for RP1 DNA were further tested for the presence of live virus (TCID50 assay).ResultsRP1 DNA was detected in blood of 37/87 (42.5%) patients and 134/791 (16.9%) samples during treatment cycles 1–8. The highest levels of RP1 DNA were in blood 6h post-injection and diminished thereafter. RP1 DNA detection in urine was minimal, with 5/86 (5.8%) patients and 8/894 (0.9%) samples testing positive. Most patients (50/87 [57.5%]) and 260/914 (28.4%) samples had RP1 DNA on the surface of injected lesions sometime during treatment. The incidence of RP1 DNA from dressings was lower than that from the injection site (18/68 [26.5%] patients; 43/525 [8.2%] samples), indicating that dressings act as a barrier to RP1 DNA. We found no live virus, per TCID50, from RP1 DNA-positive injection sites and injection-site dressings. RP1 DNA was rarely detected in oral mucosa, and mostly at low levels (15/87 [17.2%] patients; 18/931 [1.9%] samples). During follow-ups, RP1 DNA was only detected on the surface of injected lesions, with 4/56 (7.1%) and 3/42 (7.1%) patients testing positive for RP1 DNA at 30 and 60 days, respectively, after the last RP1 injection. To date, no RP1 DNA has been detected in swab samples from lesions that may be of potentially herpetic origin. There have been no reports of herpetic infection in patients’ caregivers or study staff.ConclusionsRP1 DNA was primarily detected on the surface of injected lesions, with dressings appearing to serve as a protective barrier against potential RP1 DNA dissemination. Importantly, there was no evidence of live virus following culture of qPCR-positive samples, and no reported cases of transmission or confirmed herpetic infection. These findings suggest that the risk of infection and transmission of RP1 to patients and caregivers is minimal.Trial RegistrationClinicaltrials.gov; NCT03767348Ethics ApprovalThe study was conducted in accordance with the ethical principles originating from the Declaration of Helsinki and was approved by the Institutional Review Board/Ethics Committee at each participating site. Written informed consent was obtained from all patients prior to the conduct of any study-related procedures.

Pancreatic neuroendocrine tumors can be classified as functional or nonfunctional based on hormone secretion. Management of each entity is different, with nonfunctional tumors being treated with traditional chemotherapy while functional tumors respond well to antihormonal therapy and immunologic agents. The conversion of one nonfunctional tumor into a functional tumor is an exceedingly rare event that complicates the overall management of these patients. In this report, we present the case of a 73-year-old woman who developed the conversion from a nonfunctional into a functional tumor and discuss the management options considered.

The Health Level 7 (HL7) organization introduced the Information Sensitivity Policy Value Set with 45 sensitive data categories to facilitate the implementation of granular electronic consent technology. The goal is to allow patients to have control over the sharing of their sensitive medical records. This study represents the first attempt to explore physicians' viewpoints on these categories. Twelve physicians participated in a survey, leading to revisions in 21 HL7 categories. They later classified 600 clinical data items through a second survey using the updated categories. Participants' perspectives were documented, and data analysis included descriptive measures and heat maps. In the first survey, six participants suggested adding 19 new categories (e.g., personality disorder), and modifying 25 category definitions. Two new categories and sixteen revised category definitions were incorporated to support more patient-friendly content and inclusive language. Fifteen new category recommendations were addressed through a revision of category definitions (e.g., personality disorder described as a behavioral health condition). In the second survey, data categorizations led to recommendations for more categories from ten participants. Future revisions of the HL7 categories should incorporate physicians' viewpoints, validate the categories using patient data or/and include patients' perspectives, and develop patient-centric category specifications.