Citations

Abstract Background Atezolizumab plus bevacizumab (A/B) received FDA approval as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC) in 2020. However, optimal subsequent treatment options are unclear. Here, we describe clinical outcomes of advanced HCC patients following first-line treatment with A/B. Patients and Methods We conducted a multi-site analysis of patients with HCC treated with first-line A/B between January 2018 and December 2022 at Mayo Clinic. This study cohort included all patients receiving second-line systemic therapy after A/B. Median overall survival (OS) and time-to-treatment discontinuation (TTD) were estimated using the Kaplan-Meier method. Child Pugh (CP) scores are also described at diagnosis, prior to first line, and prior to second-line therapy. Results Of the 342 patients who received A/B, 107 (31.3%) received second-line treatments including anti-VEGF therapy or immune checkpoint inhibitor (ICI) and were included in the final analysis. Median OS for all patients was 11.1 months from initiation of second-line therapy. Median OS was 10.7 months (95% CI: 7.2-12.8) and 15.7 months (95%CI: 6.8-NE) for those receiving anti-VEGF inhibitors and ICI ( P = .50). Median TTD for second-line therapies was 2.4 months (95% CI: 1.7-3.3) and 2.6 months (95% CI: 1.5-5.1) for anti-VEGF inhibitors and ICI, respectively (P = .87). In multivariate analyses, CP was significantly associated with survival. Conclusion Following first-line A/B treatment, there is no statistically significant difference in survival between ICI and anti-VEGF therapy, nor in time to treatment discontinuation. CP score remains an important prognostic tool.

Background The Minnesota Retaining Employment and Talent After Injury and Illness Network (MN RETAIN) is a randomized controlled study designed to evaluate early interventions promoting workforce retention among workers in Minnesota. The study compares a cohort receiving increased support for stay at work and return to work (SAW/RTW) services from healthcare organizations and resources through workforce development to a control cohort provided solely a list of SAW/RTW resources within the state they can access on their own. Objective This manuscript aims to describe the design of the MN RETAIN Phase 2 study and experience to date including enrollment. Target enrollment for Phase 2 of MN RETAIN is 3200 workers with approximately half receiving SAW/RTW services from a Return-to-Work Case Manager (RWTCM) who is embedded within the healthcare team. MN RETAIN is structured to be accessible to all workers within the state, with a focus on equity and reaching historically underserved populations. Methods Phase 2 of the RETAIN model expanded the focus from the southeast region of MN to state-wide coverage. Enrollment and services were designed to acquire a large enough cohort to reach adequate statistical power to detect differences in disability costs and rates of SAW/RTW in participating study subjects. Impact analysis of RETAIN will be performed by the federal evaluator at a future date. Results Characteristics of enrolled participants to date are summarized as well as considerations for sustainability of the program upon study completion. Conclusions To date, the study has reached diverse workers from throughout the state of MN to provide assistance with SAW/RTW.

Abstract Menopausal users of hormone replacement therapy (HRT) are at increased breast cancer risk and decreased colorectal cancer (CRC) risk compared with individuals who have never used HRT, but these opposing associations may differ by familial risk of breast cancer and CRC. We harmonized data from 3 cohorts and generated separate breast cancer and CRC familial risk scores based on cancer family history. We defined moderate or strong family history as a risk score of 0.4 or higher, where 0.4 was equivalent to a 50-year-old woman with 1 parent diagnosed with either breast cancer or CRC at 55 years of age. Of 24 486 women assessed, 1243 and 405 were diagnosed with incident breast cancer and CRC, respectively. For breast cancer, menopausal HRT ever use versus never use hazard ratios were 1.27 (95% CI = 1.11 to 1.45) for a breast cancer familial risk score below 0.4 and 1.01 (95% CI = 0.82 to 1.25) for a breast cancer familial risk score of 0.4 or higher (Pdifference = .08). For CRC, menopausal HRT hazard ratios were 0.63 (95% CI = 0.50 to 0.78) for a CRC familial risk score below 0.4 and 1.21 (95% CI = 0.73 to 2.00) for a CRC familial risk score of 0.4 or higher (Pdifference = .03). Associations with menopausal HRT use that apply to the general population may not hold for women at moderate or strong familial risk of these cancers.

SummaryGlobal obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m2), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources. Updated in 2022, ASMBS and IFSO guidelines aim to standardise MBS indications, reflecting current understanding and emphasising comprehensive preoperative assessments. Yet, clinical variability persists, necessitating consensus‐based recommendations. This modified Delphi study engaged 45 global experts to establish consensus on perioperative management in MBS. Experts selected from bariatric societies possessed expertise in MBS and participated in a two‐round Delphi protocol. Consensus was achieved on 90 of 169 statements (53.3%), encompassing multidisciplinary team composition, patient selection criteria, preoperative testing, and referral pathways. The agreement highlighted the critical role of comprehensive preoperative assessments and the integration of healthcare professionals in MBS. These findings offer essential insights to standardise perioperative practices and advocate for evidence‐based guidelines in MBS globally. The study underscores the need for unified protocols to optimise outcomes and guide future research in MBS.

Abstract The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice. The Fall 2023 Alzheimer's Association Research Roundtable (AARR) meeting served as a forum for gathering industry perspectives and feedback on these revised criteria, ensuring that the new criteria inform research, clinical trial design, and clinical care. In this article, we outline a summary of the newly proposed “Revised Criteria for Diagnosis and Staging of AD: AA Workgroup” and provide highlights from the AARR meeting in fall 2023. Highlights The Alzheimer's Association Research Roundtable (AARR) convened leaders from industry, academia, and government, to review the Revised Criteria for Diagnosis and Staging of AD: AA Workgroup , and gather industry perspectives and feedback on these revised criteria before its publication. The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the AA's Workgroup represent a significant milestone, offering objective measures for the biological and staging of AD and bridging the gap between research and clinical care. Improving the availability and accuracy of biomarkers, especially blood‐based biomarkers (BBMs) is expected to improve clinical research and enhance the applicability of these criteria in clinical practice.

Abstract Background Immunoglobulin (Ig) measurements in the clinical laboratory have been traditionally performed by nephelometry, turbidimetry, electrophoresis, and ELISA assays. Mass spectrometry (MS) measurements have the potential to provide deeper insights on the nature of these markers. Content Different approaches—top-down, middle-down, or bottom-up—have been described for measuring specific Igs for endogenous monoclonal immunoglobulins (M-proteins) and exogenous therapeutic monoclonal antibody therapies (t-mAbs). Challenges arise in distinguishing the Ig of interest from the polyclonal Ig background. MS is emerging as a practical method to provide quantitative analysis and information about structural and clonal features that are not easily determined by current clinical laboratory methods. This review discusses clinically implemented examples, including isotyping and quantification of M-proteins and quantitation of t-mAbs within the polyclonal Ig background, as examples of how MS can enhance our detection and characterization of Igs. Summary This review of current clinically available MS proteomic tests for Igs highlights both analytical and nonanalytical challenges for implementation. Given the new insight into Igs from these methods, it is hoped that vendors, laboratorians, healthcare providers, and payment systems can work to overcome these challenges and advance the care of patients.

OBJECTIVE Hounsfield units (HUs) may better predict biomechanical complications of instrumented fusion than conventional bone quality measures. Typically, noncontrast axial slices are used. This study aims to address the influence of reconstruction plane and contrast administration on measured HUs in patients undergoing lumbar spine imaging. METHODS Patients without prior spine surgery, infection, or tumor were identified for 3 groups: 1) 150 patients with high-resolution noncontrast lumbar CT, 2) 109 patients with noncontrast and contrast-enhanced lumbar CT, and 3) 100 patients with noncontrast lumbar CT and lumbar CT myelograms. Noncontrast HU measures in group 1 were compared between axial, sagittal, and coronal reconstructions. HU measures for groups 2 and 3 were compared on axial slice averages. HU measures between groups were compared using the Wilcoxon signed-rank test to investigate the presence of a statistically significant difference between groups (α = 0.05). Linear regression was also used to determine the degree of correlation between HU measures on noncontrast axial CT slices and HU measures on other sequences. RESULTS The mean patient age was 58.8 ± 15.9 years for group 1 (54.0% male), 65.5 ± 15.9 years for group 2 (61.5% male), and 65.2 ± 14.2 years (53.5% male) for group 3. Comparison of HU measures in group 1 showed significant differences across measurement modalities with the exception of axial average versus coronal average measures (p = 0.257) and sagittal average versus midsagittal measures (p = 0.726). There were significant differences in average axial HUs for each vertebral body between contrast and noncontrast lumbar CT and between CT myelography and noncontrast CT. Linear regression analysis demonstrated an extremely high correlation between measures for all methodologies (r2 = 0.950–0.986, all p < 0.001), and between contrast-enhanced and noncontrast studies (r2 = 0.870, p < 0.001). Measurements on CT myelography were significantly correlated with those in noncontrast studies, although to a lesser degree (r2 = 0.745, p < 0.001). CONCLUSIONS HU measures on noncontrast CT appear similar across multiple different planes, suggesting that a simpler methodology such as single-slice measurement on midsagittal reconstruction may allow for more rapid assessment of underlying bone quality. Consistent with prior work, contrast-enhanced CT sequences appear to reliably mirror underlying bone quality, although CT myelogram measures may vary in a more unpredictable way that precludes their use to interpret underlying bone quality. HU measures on contrast-enhanced studies are on average greater, suggesting the need for higher cutoff values.