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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 Tau‐PET tracers have been used to monitor the progression of Alzheimer's disease (AD). However, different tracers present distinct patterns of binding throughout the brain, challenging the harmonization of their findings. Leveraging the HEAD Study, the largest head‐to‐head study of tau‐PET tracers, we recently developed the Uniτ scale, which cross‐sectionally harmonizes Flortaucipir and MK6240 onto a universal tau‐PET measurement. Here, we provide a preliminary evaluation of the Uniτ scale's longitudinal performance in HEAD and two independent cohorts. Methods We assessed 422 individuals across the AD spectrum with longitudinal tau‐PET from three cohorts: HEAD [13 cognitively unimpaired (CU), 9 cognitively impaired (CI) individuals, scanned head‐to‐head with Flortaucipir and MK6240], ADNI [74 CU, 208 CI, tracer: Flortaucipir], and TRIAD [72 CU, 46 CI, tracer: MK6240]. Standardized uptake ratios (SUVRs) were harmonized to Uniτ using the Uniτ Ecosystem ( unitau.app ). Braak I‐II and the Meta‐Temporal regions were used as regions of interest. Annual tau‐PET uptake change was calculated, and the effect size was defined as the mean annual change divided by its standard deviation. Results In HEAD, annual change in tau‐PET uptake in Braak I‐II across CU and CI was only detectable in MK6240 (Figure 1A). However, both tracers detected significant annual changes in the Meta‐Temporal ROI for CI (Figure 1B). In both ADNI (Flortaucipir) and TRIAD (MK6240), changes in tau‐PET uptake in Braak I‐II regions were not significant (Figures 2‐3A). However, across all cohorts, the Meta‐Temporal ROI consistently showed detectable annual tau‐PET increases—most pronounced among CI—leading to larger effect sizes than in Braak I‐II (Figures 1‐3B). The Uniτ harmonization did not fundamentally alter the pattern of the findings. However, in ADNI (Flortaucipir), Uniτ yielded a slightly higher effect size than SUVR in CU for both Braak I‐II and Meta‐Temporal regions. Conclusion In this large longitudinal sample, our findings confirm that Flortaucipir and MK6240 can detect tau PET changes over time likely associated with the progression of tau tangle pathology. While MK6240 appears to show greater progression in CU, both tracers progress similarly in CI. Our data also suggested that Uniτ harmonized tau PET measurements maintain the longitudinal characteristics of each tau PET tracer for use in clinical trials.

Abstract Background Red blood cell (RBC) transfusion may be lifesaving, however transfusion-transmitted infections (TTI) and transfusion-associated graft-versus-host disease (TA-GVHD) still pose a threat despite current donor selection and testing requirements. Amustaline (S-303)/glutathione (GSH) pathogen reduction (PR) is designed to inactivate infectious microbes and leukocytes in RBCs. The RedeS study evaluates the safety and efficacy of amustaline/GSH PR-RBCs compared to conventional RBCs in a broad spectrum of patients requiring acute and/or repeated RBC transfusion support. Methods RedeS is a Phase 3, prospective, multi-center, randomized, double-blind, active-controlled, parallel-design study, with a 6-month extension option to evaluate patients requiring repeated transfusions including red cell exchange (RCE).Eligible subjects will be stratified according to site, baseline bleeding status and participation in the extension period. The study arms include a transfusion period of 28-days for anemia with any bleeding or non-bleeding patients or a 28-day+6-month extension for non-bleeding patients with chronic anemia requiring repeated simple transfusions, or for patients with sickle cell disease (SCD) expected to receive three RCE procedures. The study will seek to enroll 600-800 subjects in the overall safety analysis, including ~140 repeatedly-transfused subjects in the 6-month extension including up to 30 subjects receiving three RCE procedures. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days after the last study transfusion, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to PR-RBCs. The primary efficacy endpoint is the hemoglobin (Hb) increment in subjects who are non-bleeding at baseline, adjusted for the grams of Hb transfused and averaged over multiple transfusions. With 352 evaluable transfused non-bleeding subjects (176 per treatment group) from either arm, the study will have 80% power to demonstrate non-inferiority, defined as a Hb increment treatment difference of no more than 15% of the Control group mean, assuming a Control arm coefficient of variation of 50%. Discussion RedeS will characterize the safety of amustaline/GSH PR-RBCs and is designed to demonstrate the non-inferiority of PR-RBCs to conventional RBCs with respect to Hb increment, a common pragmatic clinical assessment of RBC transfusion effectiveness.

BACKGROUND AND OBJECTIVES: Anterior lumbar interbody fusion (ALIF) is a powerful procedure for sagittal correction and indirect decompression in the lumbar spine, though aggressive correction can cause stretch neuropraxia and implant subsidence. The aim of this study was to identify radiographic and clinical predictors of segmental correction, as well as to evaluate the degree to which segmental correction on supine intraoperative radiographs translates to postoperative upright alignment changes. METHODS: We identified patients treated with 1- or 2-level ALIF at a tertiary care center and extracted data on demographics, spinopelvic parameters, and surgical details. Patients treated with isolated ALIF and ALIF with supplementary posterior instrumentation were compared on pre- and postoperative intradiscal lordosis (IDL) and change in IDL. Multivariable linear regression was performed to identify independent predictors of postoperative IDL. RESULTS: We included 204 patients (median age 57 years, 55.4% male) treated at 258 levels, of whom 114 (55.9%) underwent supplementary posterior fixation and 150 (73.5%) underwent single-level implantation. Across all patients, postoperative IDL was significantly greater than preoperative segmental lordosis (25.4° vs 15.3°; P < .001). Standalone ALIF achieved less ΔIDL than circumferential fusion for L5/S1 procedures (7.4° vs 11.6°; P < .001), though ΔIDL for L3/4 and L4/5 was similar between the standalone and circumferential groups. Multivariable analysis showed postoperative IDL to be predicted by greater preoperative IDL (β = 0.26° per degree; [0.15, 0.36]; P < .001), L5/S1 [vs L4/5] implantation (β = 3.97°; [2.72, 5.21]; P < .001), use of supplementary posterior fixation (β = 1.80°; [0.70, 2.89]; P < .001), and greater implant lordosis (β = 0.62° per degree; [0.44, 0.79]; P < .001). CONCLUSION: Postoperative IDL after 1- or 2-level ALIF is best predicted by placement of larger interbody sizes, L5/S1 implantation, greater baseline IDL, and use of adjunct posterior fixation. Patients with higher preoperative lordosis experienced smaller postoperative increases in IDL, though this was likely influenced by a treatment bias.

Abstract Background Tau‐PET imaging enables in vivo detection of tau pathology in Alzheimer’s disease (AD), with early detection being critical for tracking disease progression. Here, we compare [ 18 F]FTP and [ 18 F]MK6240 in individuals with low tau burden. Method 450 individuals from the HEAD study (22 cognitively unimpaired (CU) young (CUY), 242 CU old and 186 cognitively impaired (CI)) underwent [ 18 F]FTP and [ 18 F]MK6240 tau‐PET and amyloid‐PET scans. Scans were processed using identical pipelines with inferior cerebellar gray matter as the reference region. Individuals were categorized as low tau if both [ 18 F]FTP and [ 18 F]MK6240 meta‐temporal SUVR were lower than 1.5. For comparison, [ 18 F]MK6240 and [ 18 F]FTP were transformed into one another using linear and non‐linear models; additionally, images were also z‐scored relative to the CUYs. Result Despite cognitive status and amyloid burden, several individuals showed elevated [ 18 F]FTP retention in temporal regions relative to [ 18 F]MK6240. As an example, Figure 1 shows [ 18 F]FTP and [ 18 F]MK6240 in 16 participants (4 per cognitive and amyloid status). Across most subjects with SUVRs<1.5, [ 18 F]FTP presented higher retention in meta‐temporal region as compared to [ 18 F]MK6240, though [ 18 F]MK6240 increased sharply above this threshold (Figure 2). In Figure 3, group‐average images and their transformed counterparts are shown for each group by amyloid and cognitive status, the subset of low‐tau participants in Aβ+ groups are also shown. In low tau groups, [ 18 F]FTP meta‐temporal retention is high in comparison to [ 18 F]MK6240. Additionally, z‐scored [ 18 F]FTP images show broader spread into temporal regions than [ 18 F]MK6240, reinforcing differences in retention. Conclusion [ 18 F]FTP shows meta‐temporal retention not seen with [ 18 F]MK6240 in low tau individuals. This discrepancy persists across transformed and z‐scored images, suggesting that there is a difference in early tracer retention between [ 18 F]FTP and [ 18 F]MK6240. It is unclear if the early [ 18 F]FTP retention is related to early maturity levels of tau or off‐target signal. These findings have important implications for basic understanding of early tau retention, early diagnosis, and biomarker harmonization efforts.

Abstract Background Ten years after the original publication, the Centiloid framework is now broadly used to harmonize amyloid‐PET quantification, facilitate data sharing and comparison across cohorts, and even assist visual interpretation in clinical settings. We evaluated the global implementation of Centiloids by comparing their distribution and corresponding positivity thresholds across cohorts. Methods We gathered data from publicly available cohorts and reached out to investigators across the world to collect cross‐sectional Centiloids, demographic and clinical information, and visual read data. Gaussian mixture models (GMM, k=2) were fitted to Centiloid values for each cohort and cutoffs were calculated as mean + 2SD of the lower Gaussian. When visual reads were available, we determined Centiloid cutoffs that maximized correspondence with visual reads (Cohen’s kappa). Data was combined across cohorts using random effects meta‐analyses. Results As of January 2025, we included 37 cohorts ( n = 41,678 participants) with heterogeneous pipelines, radiotracers, and clinical and demographic characteristics (Table‐1). The low Gaussian peaks ranged from ‐9 to 10CL; the meta‐analysis identified a common peak at 1CL. The second peaks were more heterogeneous (range=38‐102CL; meta‐analysis outcome=64CL). Across cohorts, the proportion of cognitively unimpaired versus impaired participants impacted the position of both peaks, with better separation in cohorts enriched in impaired individuals (Figure‐1C). The meta‐analysis indicated a GMM‐based cutoff of 19CL (95%CI: 16‐21CL, Figure‐1B); subgroup analyses showed no evidence of significant effect between single versus multicenter settings (17 versus 20CL, p = 0.30), MRI‐based or PET‐only processing (18 versus 19CL, p = 0.88), and no evidence of difference across radiotracers (Flutemetamol: 16CL; PIB: 17CL, Flutafuranol: 18CL, Florbetaben: 19CL, Florbetapir: 20CL, p = 0.78). In a subset of 29,496 participants with visual reads available, binary visual reads corresponded well to Centiloids (common kappa=0.86, Figure‐2A). The visual read‐based cutoff of 24CL (95%CI: 21‐27CL, Figure‐2B) maximized correspondence between visual read and quantification and was slightly higher than the GMM‐based cutoff. All meta‐analysis models showed high non‐random heterogeneity (I 2 >80%) across studies, suggesting non‐random differences in peaks and cutoffs. Conclusions Meta‐analysis‐based cutoffs align well with thresholds from the existing literature. High heterogeneity among studies underscores the need to investigate contributing factors, raising concerns about applying common cutoffs.

Abstract Background Tau‐PET tracers are essential for visualizing pathology in Alzheimer’s (AD). High detectability to tau is crucial for early detection and monitoring of tau deposition. This study compares the noise to dynamic range ratio (NRR) of [ 18 F]FTP, [ 18 F]MK6240, [ 18 F]PI2620, and [ 18 F]RO948, cross‐sectionally and longitudinally. Methods 460 individuals from the HEAD study (23 cognitively unimpaired (CU) young, 249 CU old and 188 cognitively impaired) underwent [ 18 F]FTP and [ 18 F]MK6240 tau‐PET scans; 94 additionally received [ 18 F]PI2620 and [ 18 F]RO948. A subset of 28 individuals (15 CU and 13 CI) underwent [ 18 F]FTP and [ 18 F]MK6240 follow‐up scans (1.5 ± 0.1 years later). Annual change was measured as [(followup‐baseline)/time between scans]. Noise was calculated as the standard deviation (SD) of CU Aβ‐ participants aged ≤65 (SD CUAβ‐≤65 ). The dynamic range was calculated as the SD across all subjects (SD range ). A lower the NRR (=SD CUAβ‐≤65 /SD range ) indicates more detectability. Analyses were performed at both region‐of‐interest and voxel‐wise levels. Results Across the whole cohort, [ 18 F]MK6240 exhibited lower NRR than [ 18 F]FTP in all regions. Voxel‐wise, differences were most pronounced in the frontal medial temporal regions (Figure 1). Within the four‐tracers subset, [ 18 F]PI2620 and [ 18 F]FTP showed the highest NRR in Braak II, followed by [ 18 F]RO948 and [ 18 F]MK6240. In Braak IV‐VI, [ 18 F]MK6240 consistently demonstrated the lowest values, followed by [ 18 F]PI2620, [ 18 F]FTP and [ 18 F]RO948. Similarly, in metatemporal‐ROI and Braak III, [ 18 F]MK6240 remained the lowest, however followed by [ 18 F]FTP, [ 18 F]PI2620 and [ 18 F]RO948 (Figure 2). Lower [ 18 F]MK6240 NRR was due to larger SD range , while [ 18 F]FTP's lower values stemmed from smaller SD CUAβ‐≤65 . Conversely, high [ 18 F]PI2620 and [ 18 F]RO948 values are driven by larger SD CUAβ‐≤65 . Longitudinal analyses further confirmed that [ 18 F]MK6240 exhibited the lowest NRR across the entire brain, including AD‐related regions, with voxel‐wise differences mainly in the temporal and parietal lobes. Conclusion Tau‐PET tracers exhibit significant variability in detectability. [ 18 F]MK6240 consistently demonstrated lower NRR, implying better detectability across all regions, cross‐sectionally and longitudinally. Despite differences in NRR, [ 18 F]FTP, [ 18 F]RO948 and [ 18 F]PI2620 followed similar pattern. These results provide insights into the differential tracer detectability, helping guide their optimal use in detecting and tracking tau pathology. Ongoing follow‐up scans will further clarify longitudinal tracer detectability and its implications for tau progression in AD.

Abstract Background Tau‐PET tracers have been used to monitor the progression of Alzheimer’s disease (AD). However, different tracers present distinct patterns of binding throughout the brain, challenging the harmonization of their findings. Leveraging the HEAD Study, the largest head‐to‐head study of tau‐PET tracers, we recently developed the Uniτ scale, which cross‐sectionally harmonizes Flortaucipir and MK6240 onto a universal tau‐PET measurement. Here, we provide a preliminary evaluation of the Uniτ scale’s longitudinal performance in HEAD and two independent cohorts. Methods We assessed 422 individuals across the AD spectrum with longitudinal tau‐PET from three cohorts: HEAD [13 cognitively unimpaired (CU), 9 cognitively impaired (CI) individuals, scanned head‐to‐head with Flortaucipir and MK6240], ADNI [74 CU, 208 CI, tracer: Flortaucipir], and TRIAD [72 CU, 46 CI, tracer: MK6240]. Standardized uptake ratios (SUVRs) were harmonized to Uniτ using the Uniτ Ecosystem ( unitau.app ). Braak I‐II and the Meta‐Temporal regions were used as regions of interest. Annual tau‐PET uptake change was calculated, and the effect size was defined as the mean annual change divided by its standard deviation. Results In HEAD, annual change in tau‐PET uptake in Braak I‐II across CU and CI was only detectable in MK6240 (Figure 1A). However, both tracers detected significant annual changes in the Meta‐Temporal ROI for CI (Figure 1B). In both ADNI (Flortaucipir) and TRIAD (MK6240), changes in tau‐PET uptake in Braak I‐II regions were not significant (Figures 2‐3A). However, across all cohorts, the Meta‐Temporal ROI consistently showed detectable annual tau‐PET increases—most pronounced among CI—leading to larger effect sizes than in Braak I‐II (Figures 1‐3B). The Uniτ harmonization did not fundamentally alter the pattern of the findings. However, in ADNI (Flortaucipir), Uniτ yielded a slightly higher effect size than SUVR in CU for both Braak I‐II and Meta‐Temporal regions. Conclusion In this large longitudinal sample, our findings confirm that Flortaucipir and MK6240 can detect tau PET changes over time likely associated with the progression of tau tangle pathology. While MK6240 appears to show greater progression in CU, both tracers progress similarly in CI. Our data also suggested that Uniτ harmonized tau PET measurements maintain the longitudinal characteristics of each tau PET tracer for use in clinical trials.

Abstract Geroscience research benefits from interdisciplinary approaches, team science, and collaborations, which collectively facilitate the discovery of aging mechanisms and their translation into tangible, clinical interventions. Since its inception in 2019, the Midwest Aging Consortium (MAC) has provided an engaging platform for aging researchers in the United States’ Midwest to connect, collaborate, and exchange ideas. The Sixth Annual Research Symposium of the MAC held at the Mayo Clinic in Rochester, Minnesota, in April 2025 highlighted the continued impact of the MAC in bringing together aging researchers, including many trainees and early career investigators, into a collaborative environment. This record-setting event featured interdisciplinary research on key aging mechanisms, including lipid metabolism, mitochondrial dysfunction, stress response, cellular senescence, and immune adaptations across organ systems. New therapeutic concepts and clinical trial approaches were presented. Cutting-edge methodologies including single-cell and spatial transcriptomics, metabolomics, and organoid cultures, to dissect aging process in tissue-specific and systemic contexts also were presented. Overall, the MAC symposium underscored the translational potential of geroscience and reinforced the MAC’s mission to accelerate aging research through regional collaborations and innovation.