Citations

Background: Chronic nonspecific low back pain (CNLBP) is a prevalent, disabling condition worldwide. Tuina, a traditional Chinese manual therapy, has shown potential benefits, but evidence remains limited. Objective: This study evaluated the effectiveness and safety of Tuina therapy in managing CNLBP in a U.S. population. Methods: A prospective, single-blind, randomized controlled trial was conducted at Mayo Clinic Rochester campus (February 2020-April 2024). 204 participants with CNLBP were randomized into 3 groups: Tuina (N = 68), physical therapy (N = 68), or a combination of both (N = 68). Each group received 6 treatments over 2 months. The primary outcome was pain intensity (VAS); secondary outcomes included disability (ODI), quality of life (SF-36), and adverse events. Additionally, participants completed a satisfaction survey at the end of the trial. Research Electronic Data Capture (REDCap) was used for survey data collection. Data was assessed by analysis of variance (ANOVA) for the multiple repeated measurements, Kruskal-Wallis tests, while Chi-square tests, and Bonferroni correction in SAS software. Results: 185 subjects completed the study. Significant decreases in VAS, ODI, and SF-36 Overall Physical scores were found from baseline, to post treatment and follow-up in all groups ( P < .05), while there were no significant differences in VAS, ODI, or SF-36 outcomes between the Tuina group and the other 2 groups. There were 4 adverse events observed in the trial, 1 in the Physical therapy group and 3 in the Mixed group. Only 1 transient low back pain after Tuina therapy was observed in the Mixed group but did not require treatment. The high percentage of patients who received the Tuina program was extremely helpful (n = 94/126, 77.0%). The willingness to recommend was significantly higher for Tuina compared to physical therapy (Mixed group [N = 59/62, 95.2%], Tuina group [N = 57/64, 91.9%], and physical therapy group [N = 31/59, 59.6%] ( P < .05). Conclusion: Tuina therapy showed comparable benefits to physical therapy and combined treatment of both in improving pain, function, and quality of life in patients with CNLBP. With high patient satisfaction and a favorable safety profile, Tuina appears to be a safe and acceptable non-invasive treatment option. Further studies are needed to validate these findings in the future.

Abstract Background Erectile dysfunction (ED) is a known precursor and sequela of cardiovascular disease (CVD), with ED severity predicting CVD severity. Aim This study aimed to evaluate the utility of ceramide levels in patients with ED. Methods We initiated ceramide testing in all patients with ED. We retrospectively analyzed ceramide levels from electronic records and stratified by severity of symptoms using the erectile function domain of the International Index of Erectile Function (IIEF). Outcomes The study aimed to determine whether abnormal ceramide levels were associated with ED severity and increased cardiovascular risk. Results Three hundred and fifty-four patients were reviewed, of whom 253 (71.5%) had moderate or higher ED. A statistically significant difference in abnormal ceramide values was found in patients with moderate to severe symptoms, and the odds of getting an abnormal ceramide test were increased based on the IIEF scoring alone (odds ratio [OR] 2.3 [1.04-5.12]; P-value = .034). Clinical Implications Serum ceramide testing could be beneficial in identifying cardiovascular risk in men with ED, potentially prompting cardiac referrals and lifestyle modifications. Strengths and Limitations The strengths of this study include a large sample size and the use of a well-established scale, while the limitations include the retrospective nature of the study and the need for further research to validate the findings. Conclusion Patients undergoing management for ED may benefit from serum ceramide testing and subsequent cardiac referral.

Abstract Background In the current Canadian treatment landscape for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), eligibility for autologous stem cell transplantation (ASCT) guides the choice of salvage treatment. CD19 chimeric antigen receptor T-cell (CAR-T) therapies have improved outcomes in patients with chemorefractory DLBCL, but access is limited to eligible patients. This subanalysis of the RE-MIND2 observational retrospective cohort study investigated treatment patterns for R/R DLBCL in Canada. Patients and methods Data from patients enrolled in RE-MIND2 treated between 2010 and 2020 at 2 Canadian centers were retrospectively collected from health records. Descriptive statistics were used to analyze baseline characteristics, treatment initiated, and duration of treatment by line of therapy. Results One hundred and nine patients were included; 74.2% of patients were eligible for ASCT as 2L therapy, and 45.4% received transplants. ASCT eligibility for third- (3L) and fourth-line (4L) therapy declined to 17.1% and 5.9%, respectively. Patients received a wide variety of treatments in 3 and 4L. CAR-T therapy became available in 3 and 4L by the end of 2019. Median durations of treatment were &lt;2.6 months in all lines of therapy; median time to next treatment ranged from 3.4 months in 4L to 5.3 months in 2L. Conclusion Results of our study support that ASCT-ineligible patients have a poor prognosis with conventional salvage chemotherapy. Before the availability of novel immunotherapies, no apparent standard of care was observed for Canadian patients with R/R DLBCL who were ineligible for or did not receive ASCT, especially after 2L treatment.

Abstract Background Children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency typically have height, weight, and body mass index (BMI) growth patterns that differ from the general population due to increased androgen and/or glucocorticoid exposures. With the recent surge in the development of new therapies, CAH-specific growth charts are needed to evaluate the effectiveness of these new treatments. Methods Retrospective data from patients aged 0 to 20 years with classic CAH, confirmed by hormonal testing and/or CYP21A2 genotyping, from 2 large clinical databases were analyzed. Specialized charts were developed using the lamda-mu-sigma semiparametric modeling method to generate CAH-specific percentile curves from 0 to 20 years. Nodal-point analyses were conducted to assess differences in incremental growth at 4, 8, 12, 16, and 20 years of age relative to Centers for Disease Control and Prevention (CDC) 2000 normative charts using 1-sided quantile tests and age of adiposity rebound estimated with curve derivative solutions. Results A total sample of 8692 visits from 515 patients was used. Growth (height-, weight-, BMI-for-age) channels of CAH patients were significantly different over the entire growing period and characterized by diminished pubertal spurt relative to the CDC reference. Onset of adiposity rebound based on BMI-for-age occurred earlier for CAH patients (females 3.3 years, males 3.9 years) compared to their normative counterparts (5-8 years). Conclusion Our study showed that at incremental time points throughout childhood, children with CAH collectively follow specific differences in growth trajectories as compared to unaffected children. These variations highlight the need for CAH-specific charts to assist in clinical management, appraisal of growth trajectories, and assessment of the impact of new therapies.

Abstract Objectives To implementation an automated multi-institutional pipeline that delivers breast-cancer risk integrated with polygenic risk scores, monogenic variants, family history, and clinical factors, emphasizing operational challenges and their solutions. Materials and Methods A five-stage process was executed at ten sites. Data streams from REDCap surveys, PRS and monogenic reports, and MeTree pedigrees were normalized and forwarded through a REDCap plug-in to the CanRisk API. Results Integrated risk was returned to &gt;10 000 women; 3.6% were ≥25 % lifetime risk and 0.9% carried pathogenic variants. Pipeline generated score aligns well with manual generated ones. Major barriers such as heterogeneous pedigree formats, missing data, edge-case handling, and evolving model versions were identified and resolved through mapping rules, imputations, and iterative testing. Discussion Cross-platform data harmonization and stakeholder alignment were decisive for success. Borderline-risk communication and model-version drift remain open issues. Conclusion Large-scale PRS-integrated breast-cancer risk reporting is feasible but requires robust interoperability standards and iterative governance.

Abstract Aims To assess the potential for artificial intelligence-enabled electrocardiogram (AI-ECG) to serve as a long-term cardiac surveillance tool and predict left ventricular systolic dysfunction in childhood cancer patients. Methods and results We assessed performance of our previously established AI-ECG model to predict left ventricular ejection fraction (LVEF) ≤50% and ≤40% in patients with childhood cancer during internal testing (Boston Children’s Hospital) and external validation (Children’s Hospital of Philadelphia). The internal test cohort comprised 447 patients [57% male; age at cancer diagnosis 11.2 (5.4–15.7) years; 1553 ECG–echo pairs at median age 13.5 (IQR 7.7–17.9) years; 6.4% with LVEF ≤50%; 1.3% with LVEF ≤40%], 28% with leukaemia, 16% with lymphoma, 8% with neuroblastoma, 8% with sarcoma, 2% with gastrointestinal cancers, 3% with genitourinary cancers, 6% with central nervous system cancers, 11% with other/unspecified cancers, and 18% with missing/unknown cancer labels. Treatment strategies included anthracyclines (35%), bone marrow transplant (7%), and radiation (1%). The external test cohort comprised 2964 patients [55.4% male; 7054 ECG–echo pairs at median age 11.6 (IQR 6.8–15.1) years; 2.5% with LVEF ≤50%; 0.9% with LVEF ≤40%]. Similar AUROCs (0.80–0.85), sensitivities (0.75–0.82), NPVs (0.986–0.996), and percent predicted negative (51–65%) were obtained across institutions to predict LVEF ≤50%, outperforming a biomarker-based model benchmark. Patients with high AI-ECG risk scores for LVEF ≤50% had higher rates of mortality [hazard ratio 3.1 (95% CI 1.8–5.3), P &lt; 0.001] compared to patients with low AI-ECG risk scores. Conclusion AI-ECG shows promise as a digital biomarker for cardiac surveillance in the vulnerable childhood cancer survivor population.

Abstract Context The impact of active hypercortisolism on sleep is incompletely characterized. Studies report impaired sleep in patients with Cushing syndrome (CS). Patients with mild autonomous cortisol secretion (MACS) demonstrate mild nocturnal hypercortisolism that could impact sleep. Objectives To characterize sleep abnormalities in patients with CS and MACS using the Pittsburgh Sleep Quality Index (PSQI), identify factors associated with poor sleep, and compare sleep abnormalities in patients with MACS vs referent subjects. Methods We conducted a single-center cross-sectional study of adults with active CS and MACS. Clinical and biochemical severity scores for hypercortisolism were calculated. Parallelly, we enrolled referent subjects. Quality of life was assessed using (1) the Short Form-36 (SF-36) in all participants and (2) the CushingQoL in patients with active hypercortisolism. Sleep quality was assessed using PSQI. Results PSQI was assessed in 154 patients with CS (mean 12, SD ±4.5), 194 patients with MACS (mean 11, SD 4.6), and 89 referents (mean 5, SD ±3.4). Patients with MACS exhibited shorter sleep duration, longer sleep latency, more severe daytime dysfunction, lower sleep efficiency, and a higher sleep medication use compared to referent subjects (P = &lt;.001 for all). Age-, sex, and body mass index-adjusted analysis demonstrated no differences in PSQI or its subcomponents between patients with CS and MACS (P &gt; .05 for all). In a multivariable analysis of patients with MACS, younger age, female sex, and higher clinical hypercortisolism severity score were associated with impaired sleep. In patients with CS, only younger age was associated with poor sleep. Conclusion Patients with MACS demonstrate sleep impairment that is similar to patients with CS. Younger women with higher clinical severity of MACS are more likely to have impaired sleep.

ABSTRACT Background The Geriatric Emergency Department (ED) guidelines recommend screening older adults for delirium using evidence‐based screening tools, but these tools are often underutilized. We aimed to identify barriers and facilitators to implementing an electronic health record (EHR)‐based delirium screening tool as intended. Methods This mixed methods and focused ethnographic study combined a review of structured delirium screening data with observations of real‐time delirium screenings and semi‐structured in‐person interviews at an academic ED that previously implemented the Delirium Triage Screen (DTS) and Brief Confusion Assessment Method (bCAM) tool. Content analysis of field notes from observations and interview transcripts was guided by the Exploration, Preparation, Implementation, and Sustainment implementation framework. Results From a total of 40,818 ED visits, 6196 (15.2%) had incomplete screens (i.e., without fidelity). We observed 62 encounters, of which 25 (40.3%) screenings were implemented without fidelity due to (1) not asking the required screening questions, (2) assuming patient responses, or (3) not completing the screen due to uncertainty regarding a patient's baseline mentation. We conducted 32 interviews. Identified barriers included staff prioritization of other tasks (e.g., stroke code, cleaning patients), limited knowledge of the screen's importance and utility, and language discordance. Facilitators included care partners providing baseline mental status information and nurses prefacing the screening to increase patient engagement. Conclusion The fidelity of ED delirium screening is influenced by an interplay of environmental, patient, provider, and caregiver factors. Fidelity may be improved by focusing education on the importance of screening, training screeners on how to determine whether a patient's mentation is acutely changed, providing clear action steps when a patient screens positive, and addressing how to administer the delirium screen to patients who do not speak English fluently.

ABSTRACT Light chain multiple myeloma (LCMM) is a subtype of multiple myeloma (MM) characterized by the exclusive production of immunoglobulin light chains and accounts for 15%–20% of newly diagnosed MM. A comprehensive comparison of LCMM with MM producing intact immunoglobulin (non‐LCMM) remains limited. In this retrospective study, we described distinct clinical and cytogenetic features and assessed long‐term outcomes in 852 LCMM patients diagnosed between 01/01/2004 and 12/31/2022, compared with non‐LCMM controls matched for age, sex, and year of diagnosis. On univariable analysis, LCMM patients were more likely to present with elevated creatinine (> 2 mg/dL), beta‐2‐microglobulin ≥ 5.5 mg/L, elevated LDH, hypercalcemia, t(11;14), del(13q), and t(6;14). Conversely, IMS‐IMWG high‐risk disease, hyperdiploidy, t(4;14), and serum albumin < 3.5 g/dL were less common. On multivariable analysis, elevated creatinine (OR: 5.1, 95% CI: 1.2–27, p = 0.04), t(11;14) (OR: 2.6, 95% CI: 1.3–5.2, p = 0.006), and del(13q) (OR: 4.1, 95% CI: 2.1–8.2, p < 0.001) were independently associated with LCMM, while IMS‐IMWG high‐risk disease (OR: 0.3, 95% CI: 0.1–0.8, p = 0.02) and hyperdiploidy (OR: 0.3, 95% CI: 0.1–0.7, p = 0.002) were less frequent. Despite these differences, progression‐free survival with frontline treatment (HR: 0.97, 95% CI: 0.84–1.11, p = 0.63) and overall survival (HR: 0.99, 95% CI: 0.87–1.13, p = 0.94) were similar between LCMM and non‐LCMM patients. This study highlights the distinct clinical and cytogenetic features of LCMM, marked by higher rates of renal failure, t(11;14), and del(13q), lower prevalence of IMS‐IMWG high‐risk disease, and comparable survival outcomes.