Swedish Medical Center

Spondyloarthritis (SpA), including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), comprises a diverse but interrelated family of inflammatory diseases characterized by inflammation of the joints and spine. Signs and symptoms of SpA vary widely, as patients experience a diverse spectrum of musculoskeletal and extra-musculoskeletal disease manifestations. Interleukin (IL)-17 is an inflammatory cytokine common to the pathogenesis of SpA disease development and progression. The IL-17A inhibitor secukinumab has been well established in clinical trials and real-world practice as an effective therapeutic tool to efficiently manage SpA indications axSpA and PsA in adults, as well as juvenile PsA (jPsA) and enthesitis-related arthritis (ERA), which are two subtypes of juvenile idiopathic arthritis. This review highlights the comprehensive response to IL-17 inhibition with secukinumab across SpA indications of PsA, axSpA, and ERA/jPsA and within each indication according to established disease domains. We provide context through expert commentary on the effect of inhibiting IL-17 with secukinumab on the full spectrum of SpA disease manifestations, as well as areas in need of further investigation.

B-cell maturation antigen (BCMA)-targeting therapies provide a new approach to treating multiple myeloma (MM). Alnuctamab (ALNUC) is a 2 + 1 immunoglobulin G1-based bispecific antibody binding BCMA and CD3ε receptors on myeloma and T cells, respectively. CC-93269-MM-001 is a first-in-human, phase 1 dose escalation/expansion study investigating ALNUC in relapsed/refractory MM. Patients had ≥3 prior regimens, disease progression ≤60 days of last regimen, and were BCMA-directed therapy-naïve. ALNUC was administered intravenously (IV) and subcutaneously (SC); however, SC was selected for further evaluation due to the more favorable safety profile. Ninety-five patients received ALNUC SC; at data cutoff, 44.2% remained on treatment and median follow-up was 8.0 months. The recommended phase 2 dose was 30 mg. The most common treatment emergent adverse events (any grade/grade 3/4) were CRS (57.9%/0%), and neutropenia (53.7%/43.2%). Infections were also frequent (64.2%/14.7%). ORR was 58.9% for all ALNUC SC-treated patients and 71.4% for the 30-mg cohort; 47/95 (49.5%) were measurable residual disease (MRD) negative. Overall, the safety and efficacy of ALNUC SC were comparable to other BCMA-targeted therapies. These results support improved safety of SC versus IV, and corroborate a step-up dosing strategy to mitigate CRS. Importantly, a schedule that de-intensifies over time provides favorable toxicity that may be applicable to other bispecific engagers.

Despite advances in guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction, challenges with uptitration may delay optimal treatment. Cardiac resynchronization therapy (CRT) improves clinical outcomes, yet optimal sequencing of CRT and GDMT remains uncertain. We sought to characterize longitudinal GDMT titration and evaluate associations between CRT timing and outcomes among US patients. A retrospective cohort study of 6334 Medicare beneficiaries with an identifiable incident HF diagnosis who will receive CRT between 2018 and 2022. Early CRT was defined as implantation within 1 year of diagnosis. Medication use was assessed by medication possession ratios of ≥0.8 in quarterly intervals. Outcomes were compared using propensity score overlap-weighted models. GDMT uptake increased sharply after the incident HF diagnosis but plateaued quickly with consistent medication use remaining low. Early CRT (n = 3777) was associated with lower adjusted risk of composite all-cause death or HF exacerbation (hazard ratio 0.80, 95% confidence interval [CI] 0.72-0.89), all-cause death alone (hazard ratio 0.79, 95% CI 0.69-0.90), and fewer HF exacerbations (incident rate ratio 0.66, 95% CI 0.58-0.75) vs late CRT (n = 2557). Early CRT was also associated with lower inpatient and emergency department use, Medicare expenditures, and HF-related out-of-pocket costs after CRT implant. Early CRT was associated with lower mortality, fewer HF exacerbations, and lower health care use, supporting reconsideration of GDMT and CRT treatment sequencing.

In this pilot trial, we tested the feasibility of conducting a randomized controlled trial in cardiac surgery patients using extended-, 100% plasma-, cold-stored, and long-distance-shipped platelets (CSPs). We conducted a single center, controlled, double-blind pilot study in adult patients undergoing elective redo or complex cardiothoracic surgery. Patients were allocated in a week-based block randomization scheme to receive either room temperature-stored platelets (RTPs) or CSPs shipped from a Texas-based blood center and stored between 10 and 14 days. The primary outcome was defined as the feasibility of recruitment and accrual. Several other secondary endpoints were assessed. All platelet units were screened for aggregates using RTP release criteria. In a post-hoc "as treated" analysis, 15 patients received RTPs, and 9 received CSPs (including 3 who received both). We found that most CSPs (58%) were not usable for transfusion due to the presence of aggregates. This resulted in an excess of subjects receiving RTPs; consequently, the final nine transfused participants were allocated to receive CSPs without randomization. We accrued 0.7 evaluable subjects/month of active enrollment, which was below our desired primary outcome feasibility target of ≥1.2. One death within 28 days occurred in the RTP transfusion group, while none occurred in the CSPs group. In vitro testing yielded contradictory results. Due to slow recruitment and the abundance of aggregates in CSPs, this pilot trial does not support the feasibility of the study protocol.

Background: Naloxone distribution is a key harm-reduction strategy, yet implementation in emergency departments (EDs) remains inconsistent. Best Practice Advisories (BPAs) are intended to provide timely, actionable prompts, but high alert burden can diminish their effectiveness through alert fatigue. Existing evidence largely reflects academic medical centers and focuses on naloxone prescribing rather than the distribution of take-home naloxone (THN) kits. Little is known about how naloxone-related BPAs perform in community EDs, where workflows and alert-fatigue dynamics differ.Methodology: We conducted a retrospective cross-sectional study in a suburban, non-academic ED from January 2022 to January 2024. After exclusions, 10,313 encounters with complete BPA and naloxone documentation were analyzed. Six naloxone-related BPA elements were extracted from audit logs and evaluated alongside demographic and clinical variables. Multicollinearity among BPA components was addressed using variance inflation factor (VIF)-guided pruning. Class imbalance was mitigated using SMOTE-Tomek and class weights. Logistic regression models were developed using an 80/20 train-test split, with performance assessed using area under the curve (AUC), accuracy, and sensitivity analyses.Results: Among encounters in which a naloxone-related BPA fired, clinicians overrode 25.6% of alerts and acknowledged 74.4%; however, acknowledgment translated into THN distribution in only 36.7% of encounters. This highlights a substantial gap between alert visibility and clinical action. Furthermore, BPA-related variables contributed minimal predictive signal. In adjusted models, the Emergency Severity Index (ESI) was the only significant predictor, with lower acuity associated with decreased odds of naloxone distribution. Race, ethnicity, sex, age, and all BPA-related variables were not significant predictors. The final model demonstrated moderate discrimination (AUC ≈ 0.77) with stable performance across original and SMOTE-balanced datasets. Subgroup analyses showed no evidence that BPAs improved equity in naloxone distribution.Conclusions: Naloxone BPAs in this community ED did not function as meaningful clinical signals. Although most alerts were acknowledged, they did not influence the distribution of THN kits and added minimal predictive value. Naloxone distribution reflected clinical cues, particularly acuity and opioid-related risk indicators, rather than BPA prompts. Redesign is needed to improve the timing, targeting, and relevance of naloxone-related clinical decision support (CDS). Future harm-reduction strategies should prioritize workflow-integrated, actionable CDS rather than broad, interruptive alerts that blend into background noise.

To explore young women's experiences during the pre-, peri-, and post-diagnostic phases of hormone-sensitive breast cancer and survivorship. A descriptive qualitative secondary analysis was conducted with ten women aged 28-39, diagnosed within five years and recruited via two national Swedish patient organizations. Semi-structured interviews were conducted virtually or by phone, recorded, and transcribed verbatim. Data were analysed inductively using qualitative content analysis. The analysis revealed one overarching theme, Navigating Uncertainty in the Journey Through Breast Cancer, capturing young women's experiences across diagnosis, treatment, and survivorship. Five descriptive categories illustrated key aspects of this journey: Experiences of Neglect While Seeking Care for Breast Cancer Symptoms; The Lack of Age-Specific Support in Healthcare; Seeking Knowledge, Regaining Control, and Developing Coping Strategies; Balancing Parenthood and Cancer Treatment; and Existential Anxiety and the Importance of Addressing Mortality. Young women with hormone-sensitive breast cancer face unique challenges related to age bias, limited reproductive and psychosocial support, and existential distress. Tailored, age-sensitive, person-centered care is essential to address these needs and improve survivorship experiences.

BackgroundPrior research explored the effect of elevation on deep vein thrombosis (DVT) but primarily examined injuries at elevations <1000 or >4000 feet, excluding elevations in between, and focused on specific subsets of trauma patients. This study aimed to conduct a more detailed analysis of the relationship between elevation and DVT in all trauma admissions.MethodsThis retrospective cohort study at four level I trauma centers included adult trauma patients (October 1, 2022 to October 1, 2023). Injury zip codes were used to define elevation. High-elevation (H-ELV) injuries (≥5000 feet) were compared with low-elevation (L-ELV) injuries (<5000 feet). Elevation was further categorized into 1000-foot increments. An alpha of <0.0001 defined statistical significance.ResultsOf 8620 patients, 49% (4231) had L-ELV injuries and 51% (4389) had H-ELV injuries. Compared to patients with L-ELV injuries, those with H-ELV injuries were significantly older, had lower oxygen saturation and higher heart rate, suffered falls and sports injuries more often, and motor vehicle collisions less often, and had a higher rate of comorbidities, including alcohol use disorder and anticoagulant use. DVTs occurred significantly more often after H-ELV injuries than L-ELV injuries (1.9% vs. 0.5%, p<0.0001). For each 1000-foot increase in elevation, there was a corresponding 0.4% average increase in the rate of DVT (moderate R2=0.6). After adjustment for alcohol use disorder and oxygen saturation, H-ELV injuries were associated with a 3.8-fold increase (95% CI 2.3 to 6.4) in the risk of DVT when compared with L-ELV injuries.ConclusionsEven after adjustment, H-ELV injuries were associated with 3.8 increased odds of developing a DVT compared with L-ELV injuries. There was a significant positive linear association between DVT and injury elevation, with the rate of DVT increasing with increasing elevation. This finding may suggest the need for enhanced screening or tailored DVT prophylaxis methods at higher elevation trauma centers to improve outcomes.Level of evidenceLevel IV.