Citations

Abstract A novel stationary tomographic Ultra-Fast Molecular Breast Imaging (UFMBI) technology was developed to reduce acquisition time and radiation dose of Molecular Breast Imaging (MBI), enabling its wider acceptance for supplemental dense breast screening. The system combines a stationary dual-head gamma camera made of CZT detectors with densely packed multi-pinhole collimators and novel de-multiplexing reconstruction methods, exploiting the ultra-high 3D position resolution of CZT detectors and their excellent energy resolution. A small field-of-view prototype (132 mm × 88 mm) was designed, built and calibrated. Raw detector data were processed using a machine-learning model providing 10×10 subpixelisation of 2 mm pixels in 5 mm thick CZT detectors and depth-of-interaction (DOI) estimation from anode signals alone. Tomographic images were reconstructed using an OSEM algorithm, including de-multiplexing and corrections for attenuation and collimator response. The prototype was evaluated using a 99mTc-filled phantom with lesions of different sizes and uniform background acquired separately. Prototype performance was compared with a clinical planar MBI system by imaging 99mTc-infused gel phantoms, with lesion detectability assessed via contrast-to-noise ratio (CNR). The results from the spheres’ phantom indicated that 5-7 mm diameter lesions with tumour-to-background ratios of 10-20:1 were detectable even with a dose/time reduction factor (DRF) of 8 relative to current MBI clinical practice. The gel phantom experiments showed that, with equal activity concentration and scanning time (DRF=1), the UFMBI prototype provided 2.5 to 3.9-fold CNR of the clinical planar system depending on the lesion activity and position within the field-of-view; with DRF of 6, UFMBI provided 1.6 to 2.4-fold CNR of the clinical system, improving to 2.5 to 3.4-fold with application of non-local means noise filtering. These results demonstrate the feasibility of UFMBI as a low-dose, high throughput approach and support its further development toward cancer screening of dense breasts and image-guided biopsy applications.

Abstract Rare Mendelian disorders affect 300-400 million people globally. Although genetic testing has become widely adopted, gene-specific evidence for tailored variant interpretation remains scattered across resources. We present Gene Portals, a framework for gene-centered multimodal knowledge bases that co-localize expert-harmonized clinical data, functional assays, population variation, structural annotations and gene-specific ACMG/AMP specifications within a single resource. A modular interface integrates this unified evidence with VCEP-refined ACMG specifications to enable automated gene-specific variant classification, infer molecular mechanisms, and support cross-gene analyses. We demonstrate the framework’s utility across five Gene portals spanning eleven neurodevelopmental disorder-associated genes, integrating data from 4,423 individuals with 2,838 unique variants, 36,149 ClinVar submissions, and 1,044 expert-curated molecular readouts. By organizing evidence that is otherwise dispersed across multiple sources into a unified, queryable framework, the SCN, GRIN, CACNA1A, SATB2 and SLC6A1 Gene Portals became widely used community resources and provide an extensible template for standardized rare-disease variant interpretation and mechanism-aware discovery.

Abstract Objectives To assess quantitative and qualitative image characteristics in phantoms and patients using a simultaneous ultra-high resolution (UHR) and multi-energy (ME) dual-source cardiac scan mode in a photon counting detector (PCD) CT scanner. Methods UHR-ME cardiac scans were performed to determine the spatial resolution and multi-energy performance. UHR reconstructions were completed to measure transverse and axial spatial resolution in terms of modulation transfer function (MTF) and slice sensitivity profile (SSP). Virtual monoenergetic images (VMIs), virtual non-contrast (VNC) images, and iodine concentration images were created using moderately sharp reconstruction kernels to assess ME performance. With IRB approval, coronary CT angiograms were acquired in 19 patients using the UHR-ME mode, from which iodine contrast-to-noise ratio (CNR) was measured. Various ME post-processing tasks were performed to show the utility of the spectral capabilities. Results VMIs showed a mean CT number error of 6.0%, while iodine accuracy was 0.71 mg/cc (root-mean-square-error). Spatial resolution matched well with a standard UHR mode. Patient images showed a trend of higher CNR at lower keV, while higher keV images showed decreased calcium blooming. ME techniques to separate iodine and calcium were used successfully. Conclusions The combination of UHR-ME cardiac mode retains UHR image quality while providing flexibility for ME post-processing. Advances in knowledge Cardiac UHR-ME PCD-CT scanning offers simultaneous UHR and ME imaging without loss of spatial or temporal resolution or quantitative accuracy.

Importance The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, −0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

Study Design. Retrospective cohort study of prospectively accrued data. Objective. To evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach. Summary of Background Data. The influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data. Methods. Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy. Results. A total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P=0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy (P=0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches. Conclusion. The odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM. Level of Evidence. Therapeutic Level—II

Abstract It is indeed a privilege to be an immunologist in what is arguably the golden age of immunology. From astounding advances in fundamental knowledge to groundbreaking immunotherapeutic offerings, immunology has carved out an enviable niche for itself in basic science and clinical medicine. The need and the vital importance of appropriate education, training, and certification in clinical immunology was recognized by the World Health Organization as far back as 1972. In the United States, Ph.D. scientists with board certification in medical laboratory immunology have served as directors of high-complexity Clinical Laboratory Improvement Amendments– and College of American Pathologists–certified clinical immunology laboratories since 1977. From 1977 to 2017, board certification for medical laboratory immunology was administered by the American Society for Microbiology through the American Board of Medical Laboratory Immunology examination. The American Board of Medical Laboratory Immunology examination was phased out in 2017, and in the fall of 2019, the American Society for Clinical Pathology (ASCP) Board of Certification (BOC) examination committee took on the responsibility of developing a new doctoral-level certification examination for medical laboratory immunology. This transition to the ASCP BOC represents a well-deserved and much-needed recognition of the rapid advances in and the highly specialized nature of medical laboratory immunology and its ever-increasing relevance to patient care. This new ASCP BOC certification is called the Diplomate in Medical Laboratory Immunology, and, as of April 1, 2023, it is now available to potential examinees. In this report, we describe the examination, eligibility routes, and potential career pathways for successful diplomates.

AbstractSpinal fusion surgeries are performed to treat a multitude of cervical and lumbar diseases that lead to pain and disability. Spinal interbody fusion involves inserting a cage between the spinal vertebrae, and is often utilized for indirect neurologic decompression, correction of spinal alignment, anterior column stability, and increased fusion rate. The long‐term success of interbody fusion relies on complete osseointegration between the implant surface and vertebral end plates. Titanium (Ti)‐based alloys and polyetheretherketone (PEEK) interbody cages represent the most commonly utilized materials and provide sufficient mechanics and biocompatibility to assist in fusion. However, modification to the surface and bulk characteristics of these materials has been shown to maximize osseointegration and long‐term stability. Specifically, the introduction of intrinsic porosity and surface roughness has been shown to affect spinal interbody mechanics, vascularization, osteoblast attachment, and ingrowth potential. This narrative review synthesizes the mechanical, in vitro, in vivo, and clinical effects on fusion efficacy associated with introduction of porosity in Ti (neat and alloy) and PEEK intervertebral implants.

Study Design: Retrospective cohort study. Objective: The purposes of this study were to determine the rate of improvement of significant preoperative weakness, identify risk factors for failure to improve, and characterize the motor recovery of individual motor groups. Summary of Background Data: While neck and arm pain reliably improve following anterior cervical discectomy and fusion (ACDF), the frequency and magnitude of motor recovery following ACDF remain unclear. Methods: We performed a retrospective review of patients undergoing 1–4-level ACDF at a single institution between September 2015 and June 2016. Patients were subdivided into 2 groups based upon the presence or absence of significant preoperative weakness, which was defined as a motor grade <4 in any single upper extremity muscle group. Clinical notes were reviewed to determine affected muscle groups, rates of motor recovery, and risk factors for failure to improve. Results: We identified 618 patients for inclusion. Significant preoperative upper extremity weakness was present in 27 patients (4.4%). Postoperatively, 19 of the affected patients (70.3%) experienced complete strength recovery, and 5 patients (18.5%) experienced an improvement in muscle strength to a motor grade ≥4. The rate of motor recovery postoperatively was 85.7% in the triceps, 83.3% in the finger flexors, 83.3% in the hand intrinsics, 50.0% in the biceps, and 25.0% in the deltoids. Risk factors for failure to experience significant motor improvement were the presence of myelomalacia (odds ratio: 28.9, P<0.01) and the performance of >2 levels of ACDF (odds ratio: 10.1, P<0.01). Conclusions: Patients with substantial preoperative upper extremity weakness can expect high rates of motor recovery following ACDF, though patients with deltoid weakness, myelomalacia, and >2 levels of ACDF are less likely to experience significant motor improvement.