University of Iowa Hospitals and Clinics

Left ventricular (LV) dysfunction is a potential cardioembolic source of ischemic stroke, but its role in recurrent stroke risk and treatment response remains unclear. We explore whether LV injury associates with the risk of recurrent stroke and modifies the association between anticoagulation and stroke recurrence using real-world data. We performed a multicenter, retrospective study of Cardiac Abnormalities in Stroke Prevention and Recurrence cohort across 27 US sites. Patients with LV ejection fraction ≥20% were included. LV injury, defined as LV ejection fraction 20% to 40% and wall motion abnormality, was the primary exposure and treatment effect modifier. The treatment of interest was anticoagulant versus antiplatelet therapy. The composite outcome included recurrent stroke, major bleeding, or death. Outcomes were evaluated using unadjusted and inverse probability weighting adjusted Cox proportional hazards models, with treatment effect modification tested by LV injury status. Among 2685 patients enrolled, 2328 with complete data were analyzed (median age, 65 years; 49.8% female; median follow-up, 1.6 years). LV injury was present in 310 patients (13.3%). Overall, 535 events occurred: 258 recurrent ischemic strokes, 28 hemorrhagic strokes, 67 major hemorrhages, and 256 deaths. LV injury was associated with a higher unadjusted risk of the primary outcome (hazard ratio [HR], 1.51 [95% CI, 1.21-1.87]), though nonsignificant after inverse probability weighting adjustment (adjusted HR, 1.29 [95% CI, 0.97-1.70]). In the LV injury subgroup, anticoagulation versus antiplatelet therapy was associated with a lower risk of the primary outcome (adjusted HR, 0.24 [95% CI, 0.10-0.59]), relative to the non-LV injury subgroup (adjusted HR, 1.28 [95% CI, 0.83-1.95]; p[LV-interaction], 0.001). Similar interactions were seen for EF 20% to 40% (versus >40%; adjusted HR, 0.19 [95% CI, 0.04-0.86]; p[LV-interaction], 0.001) and wall motion abnormality (versus no wall motion abnormality; adjusted HR, 0.33 [95% CI, 0.15-0.73]). After cryptogenic stroke, anticoagulation in those with LV injury was associated with lower rates of recurrent stroke, major bleeding, and death. These findings warrant confirmation in a dedicated randomized controlled trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06398366.

Curve progression to surgical range in patients with adolescent idiopathic scoliosis (AIS) is strongly associated with the initial major curve angle and the degree of skeletal maturity as staged by the modified Proximal Humerus Ossification System (PHOS) and other systems. Our purpose was to (1) develop a prognostic model and risk score to estimate the probability of progression to surgical indications in untreated patients using the PHOS and (2) compare its performance to a model using the Risser stage. Patients from the BrAIST study and 2 other institutions were followed to either skeletal maturity (Risser 4+), a major curve angle of ≥45°, or spinal fusion. Candidate variables for the predictive models included age, sex, major curve angle, Scoliosis Research Society (SRS) curve classification, status of triradiate cartilage, Risser stage, and PHOS. Model calibration and discrimination were evaluated. A probability threshold was set, creating low- and high-risk groups to aid in clinical decision-making. Overall, 164 patients (77% female) were included. The mean age at presentation was 12.2±1.4 years (range: 10 to 16 years), and the mean maximum major curve angle was 24±9° (range: 10° to 43°). Fifty-six (34%) patients progressed to a surgical range or had a spinal fusion. The PHOS model included the major curve angle and the presence/absence of a thoracic apex. The model demonstrated strong discrimination (c-statistic = 0.89) and calibration (ICI = 0.02), performing similarly to one developed in this sample using the Risser stage. The sensitivity was 0.91, the specificity was 0.71, the PPV was 0.62, and the NPV was 0.94 at the probability cut-point of 0.22. This study derived a prognostic model estimating the baseline risk of progression to surgical indications in AIS patients using the PHOS. Estimates from this model can inform the shared decision-making process and motivate compliant bracing. Further validation in larger independent samples and exploration of the PHOS to predict bracing outcomes should be performed. Level II.

PURPOSE Despite ongoing efforts, outcomes among patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Clinical trials are indispensable for therapeutic innovation, yet accrual among patients with PDAC remains suboptimal. This study aimed to identify factors associated with clinical trial offer and participation using data from a large patient survey. METHODS In collaboration with the Pancreatic Cancer Action Network (PanCAN), we conducted a Health Insurance Portability and Accountability Act–compliant electronic survey of patients and caregivers. The survey collected self-reported data on demographics, clinical characteristics, and health care access. Logistic regression was used to assess associations with clinical trial offer and participation. Multivariate models included variables significant on univariate analysis ( P < .05). RESULTS Of 1,046 sampled patients with PDAC, 284 (27.2%) were offered and 204 (19.5%) participated in clinical trials. Patients with stage IV disease had the highest odds of being offered (odds ratio [OR], 2.36 [95% CI, 1.56 to 3.53]) and participating (OR, 2.21 [95% CI, 1.40 to 3.49]) compared with those with stage I disease. Stage II/III patients were more likely to be offered trials (OR, 1.50 [95% CI, 1.04 to 2.18]), but less likely to participate (OR, 0.65 [95% CI, 0.45 to 0.94]) than those with stage IV. Treatment at academic hospitals was associated with lower odds of both trial offer (OR, 1.82 [95% CI, 1.37 to 2.44]) and participation (OR, 2.44 [95% CI, 1.72 to 3.33]) compared with community practices. Increasing age was associated with a trend toward decreased likelihood of being offered a trial (OR, 0.98 per year [95% CI, 0.97 to 1.00], P = .03). CONCLUSION Significant disparities in clinical trial access and participation persist among patients with PDAC. Targeted strategies are needed to improve trial engagement across age groups, disease stages, and treatment settings.

Anterior cruciate ligament (ACL) graft tears and contralateral ACL tears are both relatively common after primary ACL reconstruction (ACLR). There is little prior work comparing the outcomes of reconstruction after these injuries. The authors hypothesize that patient-reported outcome measures (PROMs) and activity level are lower after revision ACLR than after primary contralateral ACLR. Cohort study; Level of evidence, 3. From a cohort of 2333 patients who underwent primary unilateral ACLR, 267 were identified who underwent subsequent revision ACLR or primary contralateral ACLR within 5 years of primary ACLR. After exclusion of 11 patients who had both injuries, 256 were eligible for the study, including 124 who underwent revision ACLR and 132 who underwent primary contralateral ACLR. Patients were contacted for follow-up at 6 years after the primary ACLR, and PROMs were collected, including subjective International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score for pain (KOOS-Pain) and knee-related quality of life (KOOS-QOL), and Marx activity level. Patient demographics, surgical factors, and PROMs were compared between groups. Beta regression models with identity link were used to determine whether side of subsequent surgery (revision vs primary contralateral ACLR) was a significant predictor of outcome. Of 256 patients, 223 (87%) were contacted and completed PROMs at 6 years after the primary ACLR. At baseline, there were no significant differences between groups except that the subsequent revision group had a lower incidence of partial lateral meniscectomy and a higher incidence of lateral meniscal repair and was more likely to have received allograft for the primary ACLR than the subsequent contralateral reconstruction group. The median time from primary ACLR to second ACL surgery was lower in the revision group (1.3 years) than the contralateral group (2.0 years; P < .001). When controlling for demographics, surgical factors, and baseline PROMS, the revision ACL group demonstrated a 7.8-point lower International Knee Documentation Committee score (P < .001), a 3.2-point lower KOOS-Pain score (P = .012), a 10.4-point lower KOOS-QOL score (P < .001), and 2.0-point lower Marx score (P = .002) than the contralateral ACLR group. Patients who undergo revision ACLR within 5 years of primary ACLR demonstrate poorer PROMs and lower activity levels than those who undergo primary contralateral ACLR during this period. These 2 groups of patients should not be pooled to study outcomes of ACLR.

BackgroundHNF1B-associated disease is a genetic disorder caused by heterozygous pathogenic variants in the HNF1B gene, leading to a variety of clinical phenotypes primarily affecting the kidneys, pancreas, liver, and genitourinary tract. First identified in 1997 as the cause of MODY5 (maturity-onset diabetes of the young, type 5), the disease spectrum has since expanded to include kidney disease, pancreatic hypoplasia, genital malformations, gout, hypomagnesemia, liver abnormalities, and primary hyperparathyroidism. Variable expressivity and limited penetrance complicate diagnosis, with some individuals presenting without the classical features of partial pancreatic hypoplasia, renal developmental abnormalities or MODY. Genetic testing remains crucial for accurate diagnosis, especially in families with varied phenotypic expressions.Case PresentationThe index case, a 53-year-old woman, presented with hyperoxaluria, advanced chronic kidney disease (CKD), bilateral nephrocalcinosis, and pancreatic hypoplasia. Family members demonstrated diverse features, including renal cysts, kidney stones, diabetes, and pancreatic dysfunction. Genetic testing confirmed a pathogenic HNF1B variant (C295R) in the youngest family member, reinforcing the hereditary nature of the condition.ConclusionThis case report highlights the variable clinical presentation of HNF1B nephropathy across generations, illustrating the multisystem nature of the disease and emphasizing the importance of genetic testing for diagnosis and family screening.

Introduction: Collateral status and perfusion imaging both capture downstream flow in the occluded territory for patients with acute ischemic stroke. Collateral status can be obtained from CT/MR Angiography, which is part of the standard workflow. Perfusion imaging provides quantitative measures of blood flow and volume restrictions but requires specific set-up and commercial post-processing software. Both suffer from failure to capture changes that happened over time. Objective: We assessed if actionable information yield and prognostic utility of ischemic core measures vary based on collateral status among patients receiving Endovascular Thrombectomy(EVT) in SELECT2 with independent validation in SELECT. Methods: EVT SELECT 2 patients were stratified into those with good(Tan collateral score[TCS] of 2-3) and poor collaterals(TCS of 0-1). Ischemic core volumes were obtained from CTP processed with RAPID using rCBF&lt;30% threshold. Multivariable logistic regression models were created using age, stroke severity and time from last-known-well to procedure, without (base) and with(base + CTP core) ischemic core measures. Discrimination (AUC) and model fit using Bayesian Information Criteria(BIC) were compared, BIC reductions of 2–6, 6–10, and &gt;10 were taken as positive, strong, and very strong evidence of superior fit, respectively. SELECT trial data provided independent validation. Results: Among SELECT 2 patients, 121/178 (68%) had poor collaterals . 73/121 (61%) poor collaterals demonstrated CTP core ≥70 ml and 46(38%) ≥100 ml, whereas only 19/57 (33%) good collaterals had core ≥70 ml and 8 (14%) ≥100 ml. In poor collaterals, adding CTP core increased AUC by 0.05–0.10 and reduced BIC by 5–12 points (strong to very strong improvement) across mRS 0–2, mRS 0–3, and mortality. In good collaterals, AUC gains were minimal (0.01–0.03) (Fig 1), and BIC changes were negligible or worsened, indicating little incremental value of core. (Fig 3). SELECT showed qualitatively similar effects: poor collaterals benefited (BIC −6 to −13; AUC +0.04-0.05), while good collaterals showed ≤1-point BIC change and trivial AUC gains.(fig 2-3). Conclusions: Actionable information yield and prognostic value of CTP core volume appeared to be higher among patients with poor collaterals as compared to those with good collaterals. These findings need to be confirmed in further studies and may help with CTP acquisition decision-making for optimizing workflow and/or in limited resource settings.