Citations

Background: Lyme disease is the most common vector-borne disease in United States children. It was traditionally thought to be limited to the Northeast and upper Midwest due to the prevalence of tick and deer vectors in these regions. We hypothesize that as Lyme disease cases in children continue to increase throughout the country, nontraditional regions such as the Midwest and South may have an increased rate of Lyme disease compared with the Northeast region. Methods: The Pediatric Health Information System (PHIS) database was queried for patients 19.0 years or younger who were treated for Lyme disease between 2004 and 2019 through Emergency Department and in-patient records using ICD coding. Data from 49 pediatric hospitals was included and the centers were split into 4 regions based on geographic location. The data was separated into 2 time periods: 2004 to 2014 and 2015 to 2019. Slopes were compared using a general linear model with interaction to determine if annual rates of Lyme disease were statistically different between the 2 time periods. The data was then split by geographic region and again the annual rate of Lyme disease was compared between the 4 regions. A P -value <0.008 was considered significant to adjust for multiple comparisons. Results: Between 2004 and 2019, 7,572 cases of Lyme disease were reported with a mean age of 9.5 years (range: 0.08 to 19.00 y) and 58% male. From 2004 to 2019, there was an annual increase of 46.5 cases. When separated by region from 2004 to 2019, the Midwest had a higher increased annual rate of Lyme disease (30.7 additional cases/year) compared with the Northeast (10.0 additional cases/y), the South (3.6 additional cases/y), and the West (2.2 additional cases/y). Conclusions: Lyme disease continues to show an increased rate across the United States. The annual increase in cases in the Midwest was significantly higher than the other regions from 2004 to 2019. There does appear to be a significant regional spread, particularly in the Midwest. Awareness of the increased rate and spread of Lyme disease across the US is crucial in helping to identify national and regional strategies to diagnose and treat this disease in children. Level of Evidence: Level IV.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

OBJECTIVE Anterior cervical discectomy and fusion (ACDF) is an established treatment for cervical degenerative disc disease; however, the procedure can cause loss of cervical spine range of motion and potentially accelerate adjacent segment degeneration. Cervical disc arthroplasty (CDA) seeks to preserve native motion of the cervical spine, which can theoretically reduce the incidence of adjacent level degeneration. The literature regarding the relative efficacy of ACDF versus CDA remains inconsistent. In this study, the authors investigate the difference in outcomes between ACDF and CDA and identify factors contributing to the heterogeneity in the literature. METHODS The Ovid, Embase, Scopus, Cochrane, and ClinicalTrials.gov databases were systematically searched from inception to September 5, 2023, for randomized controlled trials (RCTs) comparing ACDF and CDA for degenerative disc disease. Studies were extracted by two authors and verified by a third. Random-effects meta-analysis was performed. The primary outcome was the difference in clinical outcomes between the two surgical groups. The secondary outcomes were the differences in radiological outcomes, surgical characteristics, complication rates, and hospital lengths of stay. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration no. CRD42023469204) and adhered to the PRISMA guidelines. RESULTS From 584 articles uploaded to the Covidence platform for screening, 35 studies derived from 25 RCTs were included in this systematic review and meta-analysis. A total of 4530 patients were treated with ACDF (2081) and CDA (2449). Forty-six percent of the patients (2063) were male, and the mean age of the study cohort was 45 ± 3 years. In terms of the primary outcome, CDA showed higher rates of neurological and overall success. Regarding the secondary outcomes, CDA demonstrated a significantly lower rate of adjacent level disease, higher rate of heterotopic ossification, and greater range of motion at the operated level. Additionally, CDA had lower rates of reoperation but significantly longer operative times than ACDF. The inclusion of myelopathic patients and variations in follow-up between the surgical groups contributed to the observed effect heterogeneity among studies. CONCLUSIONS In this study, CDA showed comparable or potentially greater success in overall and neurological outcomes, along with a lower incidence of adjacent level degeneration and reoperation rates but longer operative times.

Abstract Frailty is highly prevalent in cardiovascular disease and associates with poor clinical outcomes. Several cardiovascular conditions benefit from invasive interventions, but the impact of these procedures in frail patients remains unclear. We thus performed a systematic review and meta-analysis to summarize evidence and quantify the pooled effect of clinical outcomes of invasive cardiovascular interventions among frail vs. non-frail patients. Systematic search of two electronic databases from January 2015 to April 2025 was performed including all randomized controlled trials (RCTs) and prospective cohort studies examining outcomes of invasive cardiovascular interventions stratified by frailty. Outcomes included all-cause mortality, hospitalizations, and other adverse outcomes. Risk ratios (RRs) and their 95% confidence intervals (CI) were assessed using random-effects models. Thirty-one studies (10 RCTs, 21 prospective, 3 retrospective studies) with a total of 27 534 participants were included. Compared with non-frail patients, frail patients after cardiovascular procedures were at higher risks of all-cause mortality (RR 3.14, 95% CI: 2.29-4.30), and hospitalizations (RR 1.88, 95% CI: 1.29-2.73). Frail patients undergoing transcatheter aortic-valve implantation and percutaneous mitral-valve interventions did not have significant increased mortality risks compared with non-frail patients (P &gt; 0.05). Pre-frailty predicted lower mortality risks amongst patients undergoing transcatheter vs. surgical aortic valve replacement (HR 0.78, 95% CI: 0.67-0.92). Frail patients with non-ST elevation myocardial infarction derived similar mortality benefits from an invasive vs. conservative approach (HR 1.13, 95% CI: 0.64-2.01). In conclusion, frailty prognosticates adverse outcomes following invasive cardiovascular interventions and influences treatment efficacy, highlighting its significance in treatment selection

Abstract Magee, MK, Fields, JB, Jagim, A, Lockard, B, Miller, A, Stroiney, D, and Jones, MT. Estimation of whole-body bone mineral density through air displacement plethysmography in a large sample of elite athletes. J Strength Cond Res 39(4): 427–432, 2025—Dual-energy x-ray absorptiometry (DXA) is used to determine bone mineral density (BMD) and body composition. Regulations and cost may limit DXA's utility in some athletic settings. Air displacement plethysmography (ADP), while able to measure body composition, does not measure BMD. The purpose was to evaluate the influence of body composition parameters obtained from ADP on BMD. Collegiate athletes (males, n = 153; females, n = 208) underwent ADP and DXA assessments. For ADP testing, the Brozek equation was used to estimate body fat percent (BF%) and fat-free mass (FFM) from body density. Dual-energy x-ray absorptiometry tests were completed to obtain BMD using the whole-body scan mode. Stepwise regression was conducted using age, body mass, height, sex, race, FFM (ADP), BF% (ADP), and sport type as independent variables. Total BMD (DXA) was the dependent variable. Accuracy and precision of the final equation were evaluated through Bland–Altman and linear regression. The final regression equation yielded an R 2 of 0.691 with race, mass, BF%, age, and sport type as significant predictors ( p < 0.05) of BMD. Bland–Altman and linear regression showed systematic {95% confidence interval [CI] (−0.619 to −0.360)} and proportional bias (95% CI [0.173–0.374]). Although an ADP-derived regression equation may not provide a precise prediction of BMD, it may be useful to establish risk for low BMD if DXA is unavailable. Dual-energy x-ray absorptiometry may not be feasible for some athletic programs; therefore, an estimation equation for BMD derived from ADP values is advantageous for practitioners. This equation may assist in screening athletes for risk of low BMD.

Importance Multiparametric magnetic resonance imaging (MRI), with or without prostate biopsy, has become the standard of care for diagnosing clinically significant prostate cancer. Resource capacity limits widespread adoption. Biparametric MRI, which omits the gadolinium contrast sequence, is a shorter and cheaper alternative offering time-saving capacity gains for health systems globally. Objective To assess whether biparametric MRI is noninferior to multiparametric MRI for diagnosis of clinically significant prostate cancer. Design, Setting, and Participants A prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer (elevated prostate-specific antigen [PSA] level and/or abnormal digital rectal examination findings) from April 2022 to September 2023, with the last follow-up conducted on December 3, 2024. Interventions Participants underwent multiparametric MRI, comprising T2-weighted, diffusion-weighted, and dynamic contrast–enhanced (DCE) sequences. Radiologists reported abbreviated biparametric MRI first (T2-weighted and diffusion-weighted), blinded to the DCE sequence. After unblinding, radiologists reported the full multiparametric MRI. Patients underwent a targeted biopsy with or without systematic biopsy if either biparametric MRI or multiparametric MRI was suggestive of clinically significant prostate cancer. Main outcomes and measures The primary outcome was the proportion of men with clinically significant prostate cancer. Secondary outcomes included the proportion of men with clinically insignificant cancer. The noninferiority margin was 5%. Results Of 555 men recruited, 490 were included for primary outcome analysis. Median age was 65 (IQR, 59-70) years and median PSA level was 5.6 (IQR, 4.4-8.0) ng/mL. The proportion of patients with abnormal digital rectal examination findings was 12.7%. Biparametric MRI was noninferior to multiparametric MRI, detecting clinically significant prostate cancer in 143 of 490 men (29.2%), compared with 145 of 490 men (29.6%) (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points; P = .50). Biparametric MRI detected clinically insignificant cancer in 45 of 490 men (9.2%), compared with 47 of 490 men (9.6%) with the use of multiparametric MRI (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points). Central quality control demonstrated that 99% of scans were of adequate diagnostic quality. Conclusion and relevance In men with suspected prostate cancer, provided image quality is adequate, an abbreviated biparametric MRI scan, with or without targeted biopsy, could become the new standard of care for prostate cancer diagnosis. With approximately 4 million prostate MRIs performed globally annually, adopting biparametric MRI could substantially increase scanner throughput and reduce costs worldwide. Trial registration ClinicalTrials.gov Identifier: NCT04571840

The study assesses the relationship between thalamic proton-MR spectroscopy (1H-MRS) metabolites and thalamic 11C-ER176 translocator-protein positron emission tomography (TSPO-PET) standardized uptake value ratios (SUVR) to advance our understanding of thalamic involvement in multiple sclerosis (MS)-associated neurodegeneration and disability. In this prospective cross-sectional study, patients with MS (pwMS) and controls underwent 3T-MRI, 1H-MRS, and 11C-ER176-PET targeting the thalamus. MRI-derived thalamic volume was normalized by intracranial volume. 1H-MRS metabolites—N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln), total choline (tCho), and myo-inositol (mIns)—were normalized to total creatine (tCr). Clinical disability was evaluated using MS-specific tests of Expanded Disability Status Scale-EDSS and MS-functional composite-MSFC (including Paced Auditory Serial Addition Test-PASAT). Compared to controls (n = 30), pwMS (n = 21) exhibited smaller thalamic volume, higher thalamic 1H-MRS mIns/tCr (putative gliosis marker), and higher thalamic 11C-ER176-PET SUVR (glial density marker). In pwMS, higher thalamic mIns/tCr (r = −0.67) and tCho/tCr (r = −0.52) correlated with smaller thalamic volume. In pwMS, higher thalamic mIns/tCr correlated with higher thalamic 11C-ER176-PET SUVR (r = 0.48) and decreased cognitive function (PASAT, rho = −0.48). In controls, decreased thalamic NAA/tCr correlated with increased thalamic 11C-ER176-PET SUVR (r = −0.41). Thalamus, a core central nervous system relay, is affected early in MS disease course. Glial-mediated innate immune activation in the thalamus, evaluated by increased 1H-MRS mIns/tCr and 11C-ER176-PET SUVR, is associated with loss of thalamic volume and increased disability in pwMS. The multimodal imaging approach with 1H-MRS mIns/tCr and 11C-ER176-PET SUVR emerges as potential glial biomarkers, to better understand disease mechanisms and evaluate therapeutic interventions targeting glial activity in MS.

Abstract Obesity has been associated with non‐Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome‐wide association studies of European ancestry ( N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist‐to‐hip ratio (WHR), and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05–1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR per SD = 1.12, 95% CI: 1.02–1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.

Abstract Aims Chronotropic incompetence (CI) is a biomarker of cardiac autonomic dysfunction. The aim of the study is to assess the risk stratification value of CI during exercise or pharmacological stress echocardiography in patients with chronic coronary syndromes. Methods and results In a prospective, multicenter, international, observational study, we enrolled 13 445 patients with known or suspected chronic coronary syndromes who underwent stress echocardiography in 19 clinical sites from 10 countries using either exercise (n = 2594), dobutamine (n = 2440), or dipyridamole (n = 8411). Heart rate was automatically measured from the 1-lead ECG in the echocardiography monitor. We considered CI as failure to reach 85% of the maximal predicted (220-age) heart rate for exercise and dobutamine, and heart rate reserve (peak/rest heart rate) ≤ 1.22 (≤1.17 if in permanent atrial fibrillation) for dipyridamole stress. The primary outcome was all-cause death. CI was observed in 5045 patients (38%) and stress-induced regional wall motion abnormalities in 1648 (13%). Over a median follow-up time of 3.4 years (interquartile range, 1.6–9.1 years), there were 2426 (18%) deaths. The 10-year mortality was 39% in patients with and 21% in patients without CI (P &lt; 0.0001). CI was associated with a significant increase in 10-year mortality in all age groups ranging from ≤54 years to ≥75 years (P &lt; 0.0001). In addition, it was associated with increased mortality (P &lt; 0.0001) irrespective of β-blocker use. Cox multivariable analysis revealed that CI was an independent predictor of mortality (HR: 1.60, 95% confidence interval: 1.47–1.74; P &lt; 0.0001) together with age, male sex, diabetes mellitus, left ventricular ejection fraction, and resting heart rate. Conclusion In patients with chronic coronary syndromes, CI during exercise or pharmacological stress is a simple and objective predictor of survival.