Citations

Abstract: Heart valve abnormalities are present in 30% of congenital heart defects. Additionally, there are acquired conditions like rheumatic heart disease. They often require surgery, and in complex cases, valve replacement becomes unavoidable. The current valve replacement options, either mechanical, bioprosthetic, homografts, or autografts, lack key properties for pediatric patient needs: availability, durability, and the ability to grow. Our goal is to review 2 clinically relevant innovations: tissue-engineered heart valves (TEHVs) and partial heart transplantation (PHT). We conducted searches in electronic databases covering the past 25 years using the terms “partial heart transplantation,” “tissue-engineered heart valves,” and their combinations. Decellularized pulmonary homografts outperform cryopreserved homografts and bovine jugular vein conduits in pulmonary valve replacement, showing less stenosis and no infective endocarditis. The European Clinical Study for the Application of Regenerative Heart Valves trial confirmed decellularized pulmonary homograft safety, demonstrating 97.5% freedom from explantation at 5 years. Decellularized aortic homografts showed excellent 97.8% 5-year survival and low endocarditis rates, though increases in transvalvular gradient and regurgitation occurred. Partial heart transplantation uses living valves from donor hearts and accommodates somatic growth. Postoperative immunosuppression in PHT is required but may be limited, as children and valve tissues may possess immune privilege, as evidenced by limited valve injury even in failed orthotopic heart transplants. In a pilot study of 19 infants, with a median follow-up of 26 weeks, increases in annular diameter and leaflet length were observed. Both PHT and TEHVs are promising valve replacement options. While PHT provides a growth-adaptive capability, TEHVs hold the potential for off-the-shelf solutions with minimal immunogenicity.

ABSTRACT This review examines physiological limits, longitudinal projections, and best practices for muscle hypertrophy with a focus on bodybuilding and physique sport. Recurring body composition assessments using multicompartment models are recommended for monitoring short-term fat-free mass (FFM) changes and long-term muscular development. Normative data indicate that drug-free male athletes typically gain roughly 1.4 kg of FFM over 12 weeks of resistance training, with an interquartile range of 1–2 kg. A practical upper limit for FFM index in drug-free male athletes is approximately 28.5, although higher values have been observed in the context of elevated adiposity or anabolic androgenic steroid use. Female athletes tend to have roughly 70% less FFM at baseline but make proportionally similar FFM gains in response to resistance training. The present review models plausible short-term and long-term growth trajectories for both male and female lifters. Training practices that optimize hypertrophy include moderate loads (6–12 repetition maximum), training near muscular failure, and sufficient weekly volume (12–30 fractional sets per muscle group). Nutritional factors include maintaining modest caloric surpluses (0.1–0.25% body weight gain weekly), adequate protein intake (1.6–2.2 g/kg/d), sufficient carbohydrate intake (≥3 g/kg/d), and moderate fat intake (0.5–1.5 g/kg/d). Creatine and protein supplementation provide established hypertrophic benefits, while evidence for other supplements remains inconclusive.

Background: Hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), and preterm delivery are associated with higher long-term cardiovascular, metabolic, and kidney disease risk. Their implications for living kidney donation remain uncertain. Methods: We conducted a retrospective cohort study of 498 female living kidney donors (2000–2017) from the Mayo Clinic Living Donor Program with documented pregnancy histories, pre-donation CT angiography, implantation kidney biopsy, and measured GFR. Donors with prior HDP (n=45), GDM (n=18), or preterm delivery (n=65) were compared with donors without adverse pregnancy outcomes (APO; n=385). Kidney morphometry, histology, and function were analyzed with adjustment for age at donation and first pregnancy, parity, and hypertension. Post-donation kidney outcomes were assessed using surveys and medical record review. Results: Donors with prior HDP and GDM had higher BMI at donation (+7.9% and +8.9%; p=0.006 and 0.04), whereas donors with preterm delivery had lower BMI (−4.8%; p=0.03) compared with donors with no APO. After adjustment, donors with HDP showed no differences in kidney volumes, biopsy features, or kidney function at donation or during follow-up. Donors with GDM had larger total and cortical kidney volumes (9.5–10%), less arterial luminal stenosis, and higher 5-year post-donation eGFR (+15%; p=0.03). Donors with preterm delivery had a lower risk of eGFR <45 mL/min/1.73 m 2 (HR 0.28; p=0.03). Conclusions: Prior adverse pregnancy outcomes were not associated with adverse kidney structure at donation or accelerated kidney function decline post-donation. These findings support that APO history alone should not preclude living kidney donation when other eligibility criteria are met.

Aims Reverse shoulder arthroplasty (RSA) after prior rotator cuff repair (RCR) is commonly performed for recurrence of pain and arthritic progression; however, the influence of prior RCR timing and technique on outcomes of RSA has not been adequately explored. Our primary aim was to evaluate the relationship between the postoperative American Shoulder and Elbow Surgeons (ASES) score, whether prior RCR was performed open or arthroscopic, and the time interval between RSA and prior RCR. Secondary outcomes were forward elevation (FE) and external rotation (ER). Methods A prospectively collected single-institution shoulder arthroplasty database was queried to identify patients undergoing primary RSA after prior RCR between 2004 and 2022 for non-tumour and non-fracture indications with minimum two-year follow-up. We evaluated the relationship between the postoperative ASES score, FE, and ER stratified by prior RCR approach (open vs arthroscopic) and time between RSA and RCR. Multivariable analysis was used to adjust for potential confounders. Results We included 104 RSAs (99 patients) with a mean 8.8 years (SD 7.3) after RCR and a mean age of 68 years (SD 8.3). Prior RCR was performed arthroscopically in 40 RSAs (38%). Mean follow-up was 4.8 years (SD 2.8). On multivariable analysis, arthroscopic RCR was independently associated with a 13-point greater postoperative ASES score (p = 0.008), 14° greater forward elevation (p = 0.011), and 8° greater external rotation (p = 0.018) compared with open RCR. A ten-year increase in time between RCR and RSA was associated with a seven-point greater postoperative ASES score (p = 0.029) and 5° greater external rotation (p = 0.015). Conclusion A greater time interval between prior RCR and RSA, as well as arthroscopic techniques, is associated with improved outcomes after primary RSA in patients with prior RCR. Cite this article: Bone Joint J 2026;108-B(7):928–935.

Pollen exposure drives allergic disease in millions of Americans, yet no standardized, publicly available national pollen dataset has existed until now. We describe the first nationally standardized and publicly available dataset of pollen season timing and airborne pollen concentrations. The data were derived from the National Allergy Bureau™ (NAB™), the only pollen and mold measuring network in the United States certified by the American Academy of Allergy, Asthma & Immunology (AAAAI), and curated, processed, and disseminated by the U.S. Centers for Disease Control and Prevention (CDC). The 2003–2024 dataset provides standardized measures of (1) taxa-specific historical average main pollen season (MPS) concentrations and timing (e.g., start dates, peak dates, end dates, season length); (2) taxa-specific yearly MPS concentrations and timing; (3) grouped weekly MPS concentrations, levels, and timing; and (4) grouped daily pollen levels and MPS timing. Pollen concentrations are reported as pollen grains per cubic meter (PPCM). MPS timing is computed using a 3-day consecutive method: season start occurs after the first occurrence of three consecutive days with concentrations > 1.0 PPCM; season peak is the day of maximum concentration; and season end occurs after the first occurrence of three consecutive days with concentrations < 1.0 PPCM after the peak. Historical average timing is calculated in a 365-day-of-year format and converted to calendar dates using 2024 as a reference year for display and consistency. By combining long-term data from monitoring sites across the country, this dataset shows how pollen levels vary over time and across geographic locations. This resource supports tracking pollen trends, linking pollen with weather and climate factors, and informing public health action, clinical care, and communication about population exposure and the impact to allergic diseases such as asthma and hay fever.

Abstract Background Data on respiratory syncytial virus (RSV) acute respiratory infection (ARI) among community-dwelling U.S. adults aged 18 to 64 years, particularly those with high-risk conditions (HRC), remain limited. This study estimated incidence and attack rates of RSV-ARI and RSV lower respiratory tract disease (LRTD) in adults with and without HRCs. Methods A multistate, community-based prospective cohort of adults aged 18 to 64 years with and without HRCs was followed from October 2022 to September 2024. Incidence rates and annual attack rates of RSV-ARI and RSV-LRTD were calculated by HRC presence and age group. Results Of 3375 adults with at least 1 HRC, the RSV-ARI incidence rate was 17.9 per 1000 person-years (attack rates: year 1, 1.87%; year 2, 1.56%), compared with 14.8 per 1000 person-years (year 1, 1.33%; year 2, 1.50%) among adults without HRCs. RSV-LRTD incidence was 10.0 per 1000 person-years in adults with HRCs versus 5.7 per 1000 person-years in those without. Asthma, congenital immunodeficiency, and immunosuppressive medication use were associated with increased incidence of RSV-ARI and RSV-LRTD; whereas adults with solid organ transplant and chronic kidney disease had a significantly higher incidence rate of RSV-LRTD compared to those without these conditions. Adults aged 18 to 49 years with HRCs had significantly higher RSV-LRTD incidence (9.6 vs 4.3 per 1000 person-years). After adjustment for age and sex, having ≥1 HRC was associated with a 62% increased RSV-LRTD risk, rising to 117% among adults aged 18 to 49 years. Conclusions Adults with HRCs—particularly asthma, congenital immunodeficiency, chronic kidney disease, immunosuppressive medication use, and solid organ transplant—experienced higher RSV-ARI and RSV-LRTD incidence. The elevated RSV-LRTD burden was most pronounced in adults aged 18 to 49 years with HRCs.

Abstract Background An accurate discrete spot scanning (DSS) beam delivery time (BDT) model is essential, particularly as 4D dynamic dose accumulation calculations rely on machine‐specific time models for reliable interplay evaluation. Purpose To derive a BDT model for a synchrotron‐based Hitachi Probeat PBS proton system from oscilloscope measurements of key BDT structures, including multi‐energy extraction (MEE) characteristics. Methods Key BDT structures were characterized using oscilloscope measurements, supplemented by delivery log files where appropriate. Spot‐to‐spot scanning trajectories were visualized using a CROSSmini 2D strip ionization chamber (Liverage Biomedical Inc, Taiwan) via the dose‐driven continuous scanning (DDCS) mode. The MEE design and MEE charge recapture efficiencies were also characterized. In addition, the impact of the number of delivered spots on both the extractable fraction of charge and MEE recapture efficiency was investigated. Results An improved synchrotron‐based BDT model was derived that incorporates dead times between radiofrequency knockout (RFK) and high‐speed steering magnet (HSST) signals. Spot‐to‐spot movement follows a “hockey‐stick”‐like behavior where the effective spot‐to‐spot move time is governed by the slower axis. An energy‐dependent variation in the number of MEE layers deliverable per spill was also observed, with fewer MEE layers per spill (1–3) was observed in low and high energy ranges compared to the mid‐energy range (4–5), deviating from the nominal vendor value of five MEE layers per spill per block. A reduction in the extractable fraction of charge was observed with an increasing number of spots per spill, while increasing the number of delivered spots in the preceding layer significantly reduced the MEE recapture efficiency. Conclusion MEE characteristics should be incorporated into synchrotron‐based time models for accurate beam delivery modeling. The methodology presented here also provides a framework for centers seeking to derive machine‐specific delivery time models for their proton systems.

Abstract Recent single-cell transcriptomic studies of follicular lymphoma (FL) have revealed heterogeneity among malignant B (MB) cells and selected components of the tumor microenvironment (TME), but have been constrained by relatively small sample sizes and a lack of spatial context. We performed comprehensive cellular profiling and spatial dissection of over five million cells by integrating single-nucleus RNA sequencing (snRNA-seq) from 182 samples (FL, n = 167; control, n = 15) with single-cell spatial transcriptomics (ST) from 386 samples (FL, n = 365; control, n = 21). After stringent quality control, 1,289,073 and 3,968,427 cells from snRNA-seq and ST data, respectively, were analyzed. Unsupervised clustering of snRNA-seq data identified 58 TME cell subtypes. To extend this classification to the ST dataset, we integrated snRNA-seq and ST data by co-embedding them into a shared principal component space, enabling robust batch correction and cell-type label transfer across modalities. Using this supervised annotation framework, ST data recapitulated 54 TME cell subtypes. MB, proliferating MB (MBprolif), and healthy B (HB) cells were classified using sample-level unsupervised clustering in ST. Macrophages exhibited previously uncharacterized heterogeneity in transcriptomic profiles and spatial distribution. We identified CXCL13-expressing macrophage subtypes with high intra- and peri-follicular abundance, termed follicular macrophages (FMs). Non-negative matrix factorization of intrafollicular cell fractions identified five TME archetypes: FM, follicular stroma, two follicular T, and HB archetypes. The FM archetype was enriched for intrafollicular macrophages, including FMs, and showed a significantly higher proportion of grade 3A/3B cases (53.4%) compared to other archetypes (≤16.5%). It was also associated with a higher frequency of high tumor burden requiring treatment initiation rather than a watch-and-wait (WW) approach. Among patients managed by WW, those with the FM archetype showed significantly shorter event-free survival (EFS) compared to those with non-FM archetypes, whereas this association was not observed among treated patients. The percentage of intrafollicular macrophages (IFMP) showed excellent predictive performance for the FM archetype (area under the curve: 0.90). IFMP calculated in a published multiplex spatial protein imaging dataset from an independent cohort of 242 FL patients validated the associations between high IFMP and both pathology grade 3A/3B and shorter EFS in WW patients. Consistently, spatial neighborhood and cell–cell communication analyses revealed co-localization of FMs and MBprolif cells, forming a distinct niche with activated signaling mediated by FM-derived CXCL13, APRIL, and BAFF. Our integrative multi-modal analysis defines previously unrecognized cellular heterogeneity and spatial architecture in FL and highlights macrophage-enriched follicular ecosystems associated with aggressive clinicopathological features, providing a framework for improved biological understanding and patient management. Citation Format: Yoshiaki Abe, Bijal Thakkar, Atish Kizhakeyil, Ashley Wilson, Andrew L. Feldman, Jared Henderson, Amy Ayers, Sara Borgschatz, R. Andrew Harkins, Priya Lakra, Daisuke Kaji, Jonathon B. Cohen, David Russler-Germain, Eric Mou, Francisco Vega, Jennifer Chapman, Giorgio Inghirami, Carla Casulo, Izidore S. Lossos, Jean L. Koff, Chijioke Nze, Peter Martin, Sergei Syrbu, Kiran Vij, David L. Jaye, James R. Cerhan, Christopher R. Flowers, Anne J. Novak, Richard Burack, Dai Chihara, Mamiko Sakata-Yanagimoto, Joshua Tobin, Xubin Li, Michael R. Green. Spatially resolved microenvironment profiling reveals distinct follicular lymphoma archetypes [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A049.