Citations

ABSTRACTBackgroundThe treatment landscape for multiple myeloma continues to evolve. Recently, the addition of anti‐CD38 monoclonal antibodies (mAbs) to the triplet regimen, comprising a proteasome inhibitor, an immunomodulatory agent, and a steroid, for transplant‐eligible newly diagnosed multiple myeloma (TENDMM) has shown promising results.AimsTo evaluate the overall efficacy and safety of quadruplet therapy with an anti‐CD38 mAb compared to a triplet regimen.MethodsA systematic search of Medline, Scopus, and EMBASE databases from inception to July 2024 identified relevant randomized controlled trials (RCTs). Efficacy and safety outcomes were derived using random‐effects meta‐analysis. Summarized outcomes include hazard ratios (HR) for progression‐free survival (PFS) and overall survival (OS), odds ratios (OR) for response rates, measurable residual disease (MRD) negativity rate, and grade 3 or higher adverse events (G ≥ 3 AEs).ResultsFive RCTs involving 2963 patients were included. A statistically significant PFS was observed for quadruplet therapy when compared to the triplet regimen (HR 0.44; 95% Confidence Interval [CI] 0.35–0.56). PFS benefit was consistent for the standard risk (SR) group (HR 0.38; 95% CI 0.27–0.52) and high risk (HiR) group (HR 0.62; 95% CI 0.41–0.92). No statistically significant benefit was observed for OS (HR 0.55; 95% CI 0.28–1.08). A statistically significant benefit was observed for the overall response rate (OR 1.77; 95% CI 1.02–3.06) and MRD negativity rate (OR 2.67; 95% CI 1.79–3.99). No significant differences were observed for G ≥ 3 AE (OR 1.21; 95% CI 0.92–1.58), lymphopenia (OR 1.09; 95% CI 0.62–1.89), and anemia (OR 1.06; 95% CI 0.83–1.37). However, a significantly increased risk was observed for all‐grade thrombocytopenia (OR 1.64; 95% CI 1.37–1.97), neutropenia (OR 2.24; 95% CI 1.67–3.02) and infections (OR 1.88; 95% CI 1.07–3.31).ConclusionQuadruplet therapy demonstrated a favorable efficacy and safety profile, with consistent benefit across subgroups. The findings support its potential as the new standard of care for TENDMM.

ABSTRACTBackground and AimsNerve conduction studies (NCS) are integral to diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but their role in predicting treatment outcomes remains underexplored. This study evaluates NCS changes at first follow‐up (first NCS changes) as predictors of treatment success in CIDP, focusing on their correlation with clinical outcomes over time.MethodsNewly diagnosed CIDP patients meeting the 2021 EAN/PNS criteria were retrospectively evaluated. Baseline and first follow‐up NCS parameters were compared with clinical outcomes, assessed by the Neuropathy Impairment Score (NIS) and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. All patients received first‐line immunotherapy (intravenous immunoglobulin, corticosteroids, or plasma exchange).ResultsOf 39 treated patients, 26 (66.7%) were responders based on improving NIS trends, while 13 (33.3%) were nonresponders. Responders showed significant improvements at the first follow‐up in fibular compound muscle action potential (CMAP) amplitude, ulnar CMAP amplitude, summated CMAP amplitudes, and fibular motor conduction velocity. Changes in fibular CMAP amplitude consistently correlated with NIS (R = −0.8 to −0.6, p ≤ 0.004) and INCAT disability score improvements (R = −0.6 to −0.3, p ≤ 0.032) across all follow‐up intervals up to 60 months. Ulnar and summated CMAP amplitude changes also correlated with clinical outcomes, though their associations were less sustained than those of fibular CMAP amplitude.InterpretationThe first change in fibular CMAP amplitude is a reliable biomarker for predicting CIDP treatment response, with ulnar and summated CMAP amplitudes as alternatives when the fibular response is absent. Our findings highlight the utility of first NCS changes in monitoring and predicting treatment outcomes in CIDP.

Breast cancer is the most common malignancy among women worldwide, posing a serious threat to women’s physical and mental health. To address this significant global public health challenge, the Guidelines for the Integrated Diagnosis and Treatment of Breast Cancer with Traditional Chinese and Western Medicine working group, adhering to the principles of evidence-based medicine, has proposed a comprehensive and holistic diagnostic and therapeutic pathway. This pathway integrates the core concepts of traditional Chinese medicine (TCM), such as holistic views and syndrome differentiation and treatment, with the latest advances in breast cancer treatment from both domestic and international perspectives. It objectively evaluates the role of integrated Chinese and western medicine in the all-encompassing and full-cycle management of breast cancer across different phases: the acute phase (perioperative, chemotherapy, and radiotherapy periods), early consolidation phase, late palliative care phase, and follow-up period addressing accompanying symptoms (eg, cancer-related fatigue, bone and joint symptoms). Highlighting the unique features of TCM, the guidelines provide a model for integrated breast cancer treatment for clinicians at various levels of health care institutions. This article offers a detailed interpretation of the guideline’s key highlights and 11 PICO questions concerning TCM management throughout the breast cancer continuum, aiming to enhance the understanding, application, and promotion of the guidelines.

Abstract Although a direct link between cardiac lymphatics and congenital heart disease (CHD) has not been established, research indicates that abnormalities in the cardiac lymphatic system are involved in several congenital disorders that present with cardiac defects. However, this contribution remains poorly understood and is still an emerging area of study. One theory proposes that abnormal lymphatic development, which can present as cystic hygroma or increased nuchal translucency, may give rise to heart defects such as coarctation of the aorta, hypoplastic left heart syndrome, or bicuspid aortic valves. The genetic pathways for the development of the cardiac lymphatic system and the heart’s major vessels may overlap; therefore, mutations in these genes could result in simultaneous defects in both systems. The close anatomical proximity between cardiac lymphatics and the great vessels of the heart suggests a “cause and effect” relationship, where an abnormality in one could affect the other and lead to congenital defects. Given that congenital heart disease is the most common birth defect in the United States, this systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, seeks to explore the potential link between cardiac lymphatics and CHD. Understanding this connection could have significant clinical implications by paving the way for new diagnostic approaches and therapeutic strategies for CHDs.

Objectives The impact of body mass index (BMI) on cardiovascular risk in rheumatoid arthritis (RA) is unclear. RA characteristics may influence the association between BMI and risk. Disease activity, which predicts cardiovascular risk, is associated with obesity only among anticitrullinated antibody (ACPA)-positive patients. Biologics alter body composition and mitigate cardiovascular risk in RA. We explored the association of BMI with cardiovascular risk and whether this varied across ACPA status and biologic use. Methods We evaluated 3982 patients from an international observational cohort. Outcomes included (a) first major adverse cardiovascular event (MACE) encompassing myocardial infarction, stroke or cardiovascular death; and (b) all events comprising MACE, angina, revascularisation, transient ischaemic attack, peripheral arterial disease and heart failure. Multivariable Cox models stratified by centre risk evaluated the impact of BMI, ACPA, biologics and their two- and three-way interactions on outcomes. Results We recorded 192 MACE and 319 total events. No main effects of BMI, ACPA or biologics were observed. A three-way interaction between them on MACE (p-interaction<0.001) and all events (p-interaction=0.028) was noted. Among ACPA negative patients, BMI was inversely associated with MACE (HR 0.38 (95% CI 0.25 to 0.57)) and all events (HR 0.67 (0.49 to 0.92)) in biologic users but not non-users (p-for-interaction <0.001 and 0.012). Among ACPA-positive patients, BMI was associated with MACE (HR 1.04 [1.01–1.07]) and all events (HR 1.03 (1.00 to 1.06)) independently of biologic use. Conclusions BMI is inversely associated with cardiovascular risk only among ACPA-negative biologic users. In contrast, BMI is associated with cardiovascular risk in ACPA-positive patients independently of biologic use.

AbstractObjectiveTo examine associations with changes in quality‐of‐life (QOL) outcomes following treatment of vestibular schwannoma (VS) using stereotactic radiosurgery (SRS).Study DesignProspective longitudinal study.SettingTertiary academic center.MethodsPatients who were treated for sporadic VS using SRS from 2015 to 2022 were included. QOL outcomes were measured using the disease‐specific Penn Acoustic Neuroma QOL (PANQOL) scale.ResultsSeventy‐nine patients with pre‐SRS and at least one post‐SRS PANQOL assessments were available for analysis. The mean change in total PANQOL scores was −2 (SD 13) on a 100‐point scale. The mean duration between assessments was 4.6 years (SD 2.0). Age at SRS, sex, and SRS treatment doses were not significantly associated with changes in total PANQOL scores. Total PANQOL scores improved a mean of 4 points for patients with tumors confined to the internal auditory canal but declined a mean of 5 points for patients with tumors extending into the cerebellopontine angle (P = .01); however, these changes did not exceed the minimum clinically significant threshold of 11 points. The correlation coefficient between treated tumor volume at SRS and change in total PANQOL scores was −0.30 (P = .007). Changes in PANQOL total (P = .5) and hearing domain (P = .3) scores for patients who maintained serviceable hearing or progressed to nonserviceable hearing did not significantly differ.ConclusionTumor extent and treated volume at SRS had a statistically significant but likely not clinically important impact on total PANQOL scores. Progression to nonserviceable hearing did not have a significant impact on PANQOL total or hearing domain scores.

Background Cancers persist despite expression of immunogenic neoantigens and ongoing antitumor immune responses. While some occult tumors likely are cleared by effective antitumor immune responses, the targeted antigens are not easily identifiable as those tumors spontaneously disappear. Methods We used mouse models with a defined antigenic protein mimicking tumor-specific neoantigens to address the nature of these spontaneous anti-tumor immune responses. Results BALB/c (H-2d ) mice challenged with BALB/c breast tumors expressing the rat-erbB2 oncoprotein succumb to their tumors despite ongoing immune responses targeting tumor-specific model antigens. Meanwhile, congenic BALB.B (H-2b ) and H-2d/H-2b F1 hybrid mice spontaneously eliminate genetically matched tumors in a major histocompatibility complex (MHC)-II dependent manner. Adoptive transfer and immune cell depletion strategies revealed CD4+ T cells and CD20+ B cells are crucial mediators of the protective response in H-2b mice. Furthermore, passive transfer of immune serum from mice rejecting their tumors confers resistance in tumor antigen-tolerant animals with an inversely proportional relationship between tumor outgrowth and the amount of rat-erbB2 specific antibody present in tumor-bearing mice. Introduction of the rat-erb2 ectodomain into other H-2b tumor models also promotes their spontaneous tumor rejection. Notably, the tumor microenvironments differ in rat-erbB2+ tumor-bearing BALB.B and BALB/c mice at the time of fate decision in the models reflecting the differences between effective and ineffective tumor immune responses. Conclusions We find that the effective antitumor immunity targeting neoantigens in these breast cancer models is determined by MHC-II-restricted presentation of optimal cancer-associated antigens. These responses are dependent on CD4+ T cells, B cells, and antigen-specific antibodies.