Citations

Abstract Background Spinal implant infections (SII) are serious complications following instrumented spinal fusion. Debridement with implant retention requires antibiotic therapy, yet the optimal duration remains unclear. We assessed whether longer antibiotic duration is associated with reduced risk of treatment failure. Methods We conducted a multicenter retrospective cohort study of adult patients diagnosed with acute postoperative SII (≤90 days from index surgery) between January 1, 2017, and December 31, 2022. All patients underwent debridement with implant retention. Treatment failure was defined as unplanned reoperation, clinical recurrence, or infection-related death. A Cox proportional hazards model assessed whether being on antibiotics was protective, treating antibiotic use as a time-dependent covariate, adjusting for relevant clinical variables, and including death not attributable to infection as a competing event. A second Cox model evaluated whether shorter antibiotic duration was associated with increased risk of failure with landmark analysis at six weeks. Results There were 531 patients included in the study. Patient demographics are described in Table 1. During a median follow-up of 1,168 days (IQR 576-1,817), 151 patients experienced treatment failure. There was a non-significant trend toward decreased hazard of failure while on antibiotics (HR 0.70; 95% CI 0.46–1.05; p=0.087). Among 363 patients without early failure, 60 (16.5%) received ≤6 weeks of antibiotics and 303 (83.5%) received >6 weeks. Longer antibiotic duration was not associated with a differential risk of failure (HR 0.75, 95% CI 0.43–1.33; p=0.34). Conclusion Continuing antibiotic therapy after debridement and implant retention may help reduce the risk of treatment failure in SII. However, it remains unclear whether extending antibiotic treatment beyond a certain duration continues to offer additional benefits. Prospective studies are needed to better define the optimal duration and approach to antibiotic therapy in these scenarios. Disclosures Sandra B. Nelson, MD, UpToDate Wolters Kluwer Health: Author, Editor

Abstract Background Colonization with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) is increasingly recognized in critically ill patients and impacts infection prevention practices and empiric antibiotic selection. However, contemporary United States estimates of ESBL-E prevalence at the time of ICU admission are limited.Table 1.ICU-Specific Prevalence of ESBL Colonization at Admission Confirmed by Whole Genome SequencingFigure 1.Distribution of ESBL Gene Variants Among ESBL-Producing Enterobacterales Isolates by Bacterial Species (n = 173) Methods We conducted a prospective molecular epidemiology study of ESBL-E colonization among adult and pediatric patients admitted to nine ICUs at The Johns Hopkins Hospital between March and August 2023. Routine rectal surveillance swabs (Copan Eswab) collected at ICU admission were plated on selective chromogenic media (HardyCHROM™ ESBL) to identify third-generation cephalosporin-resistant Enterobacterales (3GCRE). Species identification was performed using MALDI-TOF MS, and ceftriaxone resistance was confirmed by broth microdilution. Whole-genome sequencing (WGS) was performed on the first isolate of each species per patient to confirm ESBL gene carriage and assess molecular features. Results Among 3,278 ICU admissions, 328 (10%) had 3GCRE isolated on admission swabs. Of these isolates, 173 (5% of all admissions) were confirmed by WGS to harbor at least one ESBL gene—representing approximately 53% of all 3GCRE isolates. ESBL-E colonization was most prevalent in the medical (10%) and cardiac (8%) ICUs. The most common ESBL-E species were Escherichia coli (72%) and Klebsiella pneumoniae (19%). Dominant E. coli sequence types were ST131 (36%), ST1193 (7%), and ST38 (6%). Nearly all ESBL genes belonged to the blaCTX-M family (95%), with blaCTX-M-15 as the predominant allele (63%). Other ESBL genes included blaCTX-M-27 (17%), blaCTX-M-14 (5%), blaCTX-M-55 (5%), and blaSHV-12 (3%). Conclusion In this large, prospective cohort, 5% of ICU patients were colonized with ESBL-E at admission, most commonly E. coli and K. pneumoniae harboring blaCTX-M genes. Phenotypic detection of 3GCRE overestimated ESBL-E prevalence by nearly 90%, highlighting the need for molecular confirmation to accurately characterize resistance. These findings suggest ESBL-E colonization remains uncommon in the U.S., even at a major referral center, supporting non-carbapenem empiric therapy in low-risk patients and reinforcing the need for targeted surveillance. Disclosures All Authors: No reported disclosures

Abstract Background The tau PET imaging with 18F‐flortacipir (18F‐FTP) has focused interest in accurately tracking longitudinal tau changes in Alzheimer's disease [1]. Thus, minimizing variability is critical. Off‐target signal has the potential to complicate interpretation of tau‐PET imaging due to potential spillover or bleed‐in effects, with increased effects seen in later stages of Alzheimer's due to cerebral atrophy and proximity of off‐target areas to relevant cortical areas[2]. Previously, we demonstrated the effect of uptake period activity on 18F‐FTP signal. With increasing recent interest in demographic factors that may affect off‐target binding, we investigated the effect of age in extra‐cerebral off‐target signal in 18F‐FTP PET imaging. Method Standard 18F‐FTP PET protocol was performed in 330 participants. Two independent readers measured tau uptake in predetermined off‐target regions, including extraocular muscle, meninges, and occipital bone among others. Linear regression models assessed the relationship between participants’ age, sex, and tau uptake values (SUV and SUVr) (SUV = (Tissue radioactivity concentration / Injected dose) / Body weight & SUVr = SUV of target region/ SUV of reference region.) Result Sex had a significant effect on off‐target signal in most brain regions, with variable positive or negative correlation based on area. Notably, SUV in the eyeball‐retina, occipital bone, upper skull meninges all showed significant positive correlation with sex, with ‘male’ status generally associated with lower SUV. The greatest effect of sex was observed in superior skull meninges, occipital bone, and internal carotid artery ( p <0.001). Age showed minimally affected SUV and SUVr in off‐target regions. SUVr values show a significant correlation with SUV values of upper skull meninges in sex. Cognitive status did not significantly affect off‐target SUV. Conclusion We observed that sex significantly affected extra‐brain off‐target signal in 18F‐FTP PET imaging, while age has minimal effect, adding to previous evidence of off‐target binding within brain regions. Further evaluation is necessary to understand the age‐related effects on off‐target regions. As a result, the variability introduced by sex may pose challenges to studying tau accumulation.

Background: One in five Americans turn to TikTok before calling their own physician. Objective: With social media on the rise as a source of health-related information, we aimed to investigate and evaluate popular content about mast cell activation syndrome (MCAS) on TikTok. Methods: Between June 14 and 16, 2024, four different MCAS-relevant phrases were searched on TikTok, and the top 50 most watched videos were analyzed independently by three subinvestigators. The global quality score (GQS) (range from 1 to 5) was applied to assess the value of the educational videos. The profession of the content creator, use of MCAS Vienna diagnostic criteria, association with postural orthostatic syndrome (POTS)/Ehlers Danlos syndrome (EDS), and information trends were also analyzed. Results: The 50 most watched MCAS-related videos collectively had > 6.5 million views, and the average number of views per video was 131,500. Most videos were created by health-care professionals (58%), including physicians (26%) and other health-care professionals (32%), whereas the minority were created by non‐health-care professionals (42%). Only one video included the MCAS Vienna criteria (2%), and 12 videos associated MCAS with POTS and/or EDS (24%). The average GQS was 1.94 (SD 0.34). Common MCAS misinformation trends included the following: inaccuracy of symptoms, diagnostic criteria, triggers, and treatment options. Conclusion: Most MCAS videos on TikTok contained misinformation, did not include key diagnostic criteria, and had poor GQS. The most viewed videos were primarily created by health-care professionals. Patients and health-care providers need to be aware of the quality of health-care information on social media.

Abstract INTRODUCTION We standardized positron emission tomography (PET) data across multiple cohorts and tracers to characterize the frequency of amyloid and tau PET severity along the clinical continuum. METHODS Clinical stage was defined using cohort‐specific criteria and included cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia. Amyloid severity was staged using Centiloids (CL). Tau severity was staged using a hierarchical Braak‐based schema. The cumulative probabilities of PET‐based stages were estimated using ordinal logistic regressions. RESULTS Among 10,396 individuals (mean [standard deviation] age: 71.9 [7.1] years), amyloid levels ≥ 25 CL increased with age among CU and MCI, while amyloid levels ≥ 100 CL were most common in dementia. In 3295 with tau PET, tau severity increased with amyloid and clinical stage and showed complex associations with age. Within each clinical stage, the full spectrum of amyloid and tau PET severity was observed. DISCUSSION PET‐based staging revealed heterogeneous amyloid and tau burden along the clinical continuum. Highlights PET‐based staging is feasible across multiple cohorts and PET tracers. There is heterogeneity in amyloid and tau severity across the clinical spectrum. The frequency of amyloid and tau PET severity increased with clinical severity. The likelihood of tau PET severity differed by age, amyloid, and clinical severity.

The treatment landscape for multiple myeloma (MM) is evolving rapidly and includes several new options. The management must be tailored to the individual. The NCCN Guidelines for MM provide a framework to base decisions regarding diagnosis, workup, treatment, and follow-up of both newly diagnosed and previously treated relapsed/refractory MM. This manuscript outlines the recommendations from NCCN Guidelines for MM specific to newly diagnosed MM (NDMM).

Abstract Background The Joint Propagation Model (JPM)‐based CenTauR scale was recently introduced to harmonize tau‐PET quantification across different radiotracers. This study examined how CenTauR harmonization enhances the comparability of tau‐PET quantification across matched cohorts using different tracers. The evaluation focused on three key aspects: (1) comparing tau‐PET positivity rates as defined by CenTauR, (2) evaluating its diagnostic accuracy for symptomatic AD, and (3) analyzing longitudinal changes in tau‐PET rates over time. Method The JPM, developed by the CPAD‐led Tau PET Harmonization Working Group (Leuzy et al., Alzheimers Dement. 2024; Figure 1A), models relationships between anchor point subjects and head‐to‐head tau‐PET SUVR data onto the CenTauR scale, providing conversion equations for multiple tracers. JPM equations were applied to [ 18 F]flortaucipir SUVR (Meta‐temporal ROI) data from 561 cognitively impaired participants in the ADNI and OASIS‐3 studies. Using ROC analysis, we determined the CenTauR cut‐off for positivity (T+) that maximized the Youden index for discriminating between FDA‐approved positive/negative visual reads. Three separate cohorts, scanned using [ 18 F]flortaucipir (ADNI), [ 18 F]MK‐6240 (CPAS), and [ 18 F]RO‐948 (BioFINDER‐2), were matched 1:1 by age, MMSE, amyloid‐β, and clinical diagnosis. CenTauR‐based metrics were compared across these cohorts. Result A cut‐off of 18 CenTauRs was found to optimally classify [ 18 F]flortaucipir PET visual reads (Figure 1B). The matching procedure identified 1089 participants (363 per cohort). The frequency of T+ using the 18 CenTauRs cut‐off for the Meta‐Temporal ROI was highly comparable across tracers across groups, except for the Aβ‐positive cognitively unimpaired group, where variability was more pronounced due to a smaller sample size (Figure 2A). Similarly, tau‐PET discriminative accuracy for symptomatic AD vs controls remained similar across [ 18 F]flortaucipir and [ 18 F]MK‐6240 (Figure 2B). In a separate sample of 212 matched participants from ADNI ([ 18 F]flortaucipir) and AIBL ([ 18 F]MK‐6240) with baseline and 1‐year follow‐up tau‐PET scans, 1‐year change in CenTauRs was comparable (Figure 2C). An exploratory voxelwise transformation, utilizing the Meta‐Temporal conversion equation in a representative case scanned with both [ 18 F]flortaucipir and [ 18 F]MK‐6240, demonstrates the potential for voxelwise CenTauR harmonization (Figure 3). Conclusion These analyses suggest that CenTauR harmonization increases the comparability of tau‐PET data acquired with different tracers. Additional validation analyses with larger cohorts including other radiotracers ([ 18 F]PI‐2620) are underway.

Abstract Background Plasma phosphorylated‐tau217 (pTau217) is a blood‐based biomarker of Alzheimer's Disease (AD) pathology. Cognitive resilience describes the presence of neurodegenerative pathology and preserved cognition. Cognitive resistance describes avoidance of neurodegeneration. This post hoc analysis of the Post‐Operative Delirium Belfast (PODB) cohort aimed to define cognitive resilience using plasma pTau217 and Mini Mental State Examination (MMSE) measures. Methods PODB was an observational cohort study, investigating people aged 65 and over, without a diagnosis of dementia, undergoing elective hip and knee replacement between 2012‐2014 with subsequent long‐term follow‐up. In this analysis, pre‐operative plasma pTau217 was used as a marker of neuropathology. A cutoff of 0.42 pg/mL was used (Ashton NJ et al. 2024). Pre‐operative and 8‐year follow‐up MMSE scores were used as a marker of cognition. A score of ≥24 was considered preserved. Definitions used were: Cognitive resilience = pTau217 ≥0.42 pg/mL plus MMSE ≥24. Cognitive resistance = pTau217 <0.42pg/mL plus MMSE ≥24. Affected = pTau217 ≥0.42 pg/mL plus MMSE <24. Those with normal markers plus poor cognition were defined as pTau217 <0.42pg/mL plus MMSE <24. These four groups were identified at baseline and follow‐up, respectively. In this analysis, 231 participants were included at baseline, 104 at follow‐up. Results Of the n = 231 participants included at baseline, n = 147/231 (64%) were cognitively resilient, n = 65/231 (28%) resistant, n = 17/231 (7%) affected, and n = 2/231 (<1%) had normal markers and MMSE <24. Of the n = 104 participants with follow‐up information included in this analysis, n = 61/104 (59%) were cognitively resilient, n = 33/104 (32%) were resistant, n = 8/104 (8%) affected, and n = 2/104 (<1%) had normal markers and MMSE <24. Cognitively resilient participants at baseline were younger ( p = 0.011) and tended to be female ( p = 0.977) compared to affected participants. At follow‐up, those who were cognitively resilient tended to be younger ( p = 0.196) and female ( p = 0.212) compared to affected participants (Table 1). Of those cognitively resilient at follow up, n = 59/61 (97%) of these participants were also cognitively resilient at baseline. Conclusions Using pTAu217, at the cut‐off quoted, we found a high incidence of cognitive resilience in an older elective surgical cohort.

Abstract Microglia are essential for maintaining brain homeostasis, including the sleep-wake cycle, but the underlying mechanisms remain unclear. Here, using in vivo two-photon imaging in both head-fixed and freely moving mice with simultaneous electroencephalogram–electromyogram (EEG–EMG) recording, we investigated microglial process dynamics and their interactions with locus coeruleus (LC) noradrenergic (NE) axons in the frontal cortex across sleep-wake states. During sleep or chemogenetic suppression of LC neurons, microglia enhanced their surveillance and increased interactions with NE axons. Correlative electron microscopy at nanometer resolution identified structural contacts between microglial process endings and NE boutons. Mechanistically, microglia-bouton interaction is primed by NE–β2-adrenergic receptor (β2AR) signaling, leading to enhanced Ca²⁺ activity in NE axons. These findings suggest that microglial interactions with NE axons promote cortical norepinephrine transmission and maintain stable wakefulness.