Citations

Abstract We conducted this systematic review to evaluate outcomes of thrombolysis followed by anticoagulation vs anticoagulation alone in pediatric patients with venous thromboembolism (VTE). This systematic review addresses mortality, VTE resolution, recurrence, bleeding, and organ-specific outcomes in 5 PICO (population, intervention, comparison, outcomes) questions on thrombolysis across pulmonary embolism (PE), extremity deep vein thrombosis (DVT), right atrial thrombosis (RAT), cerebral sinus venous thrombosis (CSVT), and renal vein thrombosis (RVT). Meta-analysis reported risk ratios or differences (95% confidence intervals [CIs]), and absolute effects per 1000 patients. Certainty of evidence was assessed using GRADE (Grading of recommendation, assessment, Development, and Evaluation) guidelines. Thirteen nonrandomized studies were included and no randomized clinical trials addressed these questions. Thrombolysis might be associated with a higher risk of major bleeding, clinically relevant nonmajor bleeding, or unspecified bleeding with risk differences of 0.09 (95% CI, −0.06 to 0.23), 0.06 (95% CI, −0.11 to 0.22), and 0.09 (95% CI, −0.04 to 0.23), respectively. In PE with hemodynamic compromise, thrombolysis might be associated with a lower risk of mortality but conclusions on PE progression were uncertain in submassive PE. In DVT, thrombolysis may have little to no effect on mortality or thrombus resolution but might be associated with lower risk of postthrombotic syndrome. In RAT, thrombolysis might have little to no effect on thrombus resolution but a higher risk of major bleeding and mortality. For CSVT and RVT, the evidence was very limited. These findings were based on very-low-certainty evidence because of confounding and imprecision from small sample sizes. This systematic review highlights key challenges in developing recommendations for thrombolysis in children with VTE.

Abstract This review explores the pivotal role of preanalytical variables in bringing liquid biopsy approaches into the clinic for brain tumors. Preanalytical variables encompass a range of critical issues, from blood sample collection and handling to the impact of tumor heterogeneity and patient-specific factors. These variables introduce challenges such as false positives, false negatives, and variability in the analysis of tumor signals, which can hinder the diagnostic and prognostic utility of liquid biopsies. Understanding the nuances of preanalytical variables is essential for the successful implementation of liquid biopsy in clinical settings. This paper delves into strategies aimed at mitigating the influence of preanalytical variables by emphasizing the importance of standardized sample collection protocols, optimized sample processing and storage, quality control measures, and the integration of multiple liquid biopsy modalities.

Recent advancements in computed tomography have significantly transformed the clinical application of this technique in diagnosing and managing coronary artery disease (CAD). Computed tomography coronary angiography (CTCA) has emerged as a leading non-invasive imaging modality, often serving as the first-line investigation to exclude obstructive CAD in patients with chronic coronary syndrome. Beyond its utility in diagnosing CAD, CTCA has become instrumental in procedural planning for percutaneous coronary intervention (PCI), particularly in complex cases such as left main stem (LMS) interventions, where peri-procedural risks are elevated. This review highlights the evolving role of CTCA in LMS PCI, underscoring its clinical utility in improving procedural precision and, subsequently, patient outcomes. Recent technological advancements, including detailed multiplanar and three-dimensional (3D) reconstructions, CT-derived fractional flow reserve (CTFFR), and the integration of artificial intelligence (AI) algorithms, have expanded the capabilities of CTCA. These innovations allow for comprehensive anatomical and functional assessments, enabling precise plaque morphology, lesion complexity, and bifurcation anatomy evaluations alongside PCI simulations. By offering detailed insights into coronary vasculature and lesion characteristics, CTCA provides critical information for optimising LMS PCI strategies. This review explores the current applications and future potential of CTCA in guiding LMS PCI, highlighting its role in improving procedural planning, risk assessment, and overall management of this challenging patient population.

Background: Total ankle arthroplasty (TAA) using patient-specific instrumentation (PSI) has increased in popularity with evidence for decreased operative duration, fluoroscopy usage, and increased implant placement accuracy. To date, no comparisons have verified the accuracy of PSI in vivo using preoperative and postoperative weightbearing computed tomography (WBCT). Our study aims to supplement the literature by quantifying the accuracy and precision of PSI-guided implant positioning using WBCT. The primary study outcome is to identify positioning deviations in degrees or millimeters in any plane for talus and tibial PSI-guided resections and subsequent implant placement. Secondary outcomes were correlation and regression analyses performed to identify variables that correlate to resection or implant placement deviation, as well as comparison to existing radiography-based PSI techniques. Methods: This was a single-surgeon, single-implant consecutive patient retrospective study where preoperative and postoperative WBCTs were obtained. TAA was performed by the senior author with the same low-profile implant for all cases. Talus and tibial resection analysis was performed in computer-automated fashion on postoperative segmented WBCTs and is described as 3 possible deviations from plan (cut height in millimeters, sagittal slope, varus/valgus deviation). Overall deformity in this group was not severe. Implant placement factors independent of PSI guides are described as center-of-mass translations (mm) and axial rotation (degrees). Desired accuracy for the PSI system was within ±2 mm or ±2 degrees of the preoperative plan. Statistical analysis of data collected included Student t test and linear regression analyses. Results: Thirty patients were included. Four talus implants were excluded per intraoperative surgeon discretion (deviation from PSI plan, use of conventional instruments). All postoperative tibial measurements were within the desired limits, except for mediolateral center of mass positioning ( P = .003) and slope ( P = .013). Two of six talar parameters also diverged from preoperative measurements: axial rotation ( P = .015) and anteroposterior positioning ( P = .002). In addition, no correlations exceeding r = 0.5 were noted between preoperative deformity measurements and postoperative positioning. Conclusion: For the 26 ankles that did not require an intraoperative deviation from PSI plan and/or use of conventional instruments, total ankle replacement performed with PSI using WBCT results in component placement with relatively little deviation from the preoperative plan. In addition, the lack of correlation between preoperative deformity and implant placement suggests that the magnitude of preoperative deformity in this group was not associated with the accuracy of PSI-guided component positioning. Level of Evidence: Level III, retrospective cohort study.

e19538 Background: Patients with multiple myeloma (MM) and type 2 diabetes mellitus (T2DM) experience increased risks of morbidity and mortality. GLP-1 receptor agonists (GLP-1 RA) offer glycemic and cardiovascular benefits, but their impact on cancer-related outcomes is unclear. This study evaluates the association of GLP-1 RA therapy with clinical outcomes, MM-related biomarkers, and survival in MM patients with T2DM. Methods: We conducted a retrospective cohort analysis using the TriNetX network, including data from 104 healthcare organizations (2014–2019). Two cohorts were defined: (1) MM patients with T2DM starting GLP-1 RA therapy within three months of MM diagnosis and continuing therapy for at least one year (n=1,606 before matching), and (2) MM patients with T2DM not receiving GLP-1 RAs (n=40,306 before matching). Patients included were aged 18 years and older. One-to-one propensity score matching (PSM) balanced systemic MM therapy, BMI, and diabetes medications (e.g., insulin, metformin), yielding 1,279 matched pairs. Outcomes included five-year mortality, ICU and non-ICU hospitalizations, and MM-related biomarkers (hemoglobin, creatinine, neutrophils, and calcium). Most recent lab values were compared in the two groups. Statistical analyses included Kaplan-Meier survival estimates, hazard ratios (HR), risk differences, and T-Test statistics. Results: After PSM, baseline characteristics were well balanced. The mean age was ~ 66 years, white race was ~46%, females were ~ 40%, and hypertension was ~85%. Around 20% of MM patients received autologous transplants and ~27% received lenalidomide in the past. GLP-1 RA therapy was associated with less mortality (HR: 0.44, 95% CI: 0.36–0.54, P < 0.01), ICU admissions (HR: 0.59, 95% CI: 0.50–0.71, P < 0.01), and non-ICU hospitalizations (HR: 0.59, 95% CI: 0.53–0.65, P < 0.01). Patients on GLP-1 RAs had higher hemoglobin levels (11.61 ± 2.30 g/dL vs. 10.75 ± 2.47 g/dL, P < 0.01), with no significant differences in serum creatinine (119.068 µmol/L vs 115.648 µmol/L, P = 0.720) or neutrophils (P = 0.226). Patients who received GLP-1 RAs had higher serum calcium levels (9.17 mg/dL vs. 8.96 mg/dL, P < 0.01). GLP-1 RA use also decreased the incidence of septic shock (HR: 0.53, 95% CI: 0.44–0.64, P < 0.001) and pneumonia (HR: 0.59, 95% CI: 0.49–0.70, P < 0.001). Conclusions: GLP-1 RA therapy improves survival, reduces ICU and non-ICU hospitalizations, and lowers complications in MM patients with T2DM. Biomarker trends over five years suggest potential anticancer effects. Further research should explore whether GLP-1 RAs impact other malignancies, broadening their role in cancer therapy.

e18503 Background: Acute Myeloid Leukemia (AML) with FLT3-ITD mutations has poor prognosis and high relapse rates after allogeneic hematopoietic stem cell transplantation (allo-HCT). Post-transplant FLT3 inhibitor (FLT3i) maintenance therapy aims to prevent relapse and improve survival. However, randomized trials vary in FLT3i potency, its use during induction, maintenance duration, and measurable residual disease (MRD) assessment, which contribute to conflicting impacts on relapse-free survival (RFS) and overall survival (OS). This systematic review and meta-analysis assessed the efficacy and safety of FLT3i maintenance versus standard-of-care (SOC) in FLT3-ITD-positive AML post-allo-HCT. Methods: A systematic review was conducted following PRISMA guidelines, focusing on randomized controlled trials (RCTs) assessing FLT3i maintenance after allo-HCT. Comprehensive searches in PUBMED, EMBASE, CENTRAL, and ClinicalTrials.gov identified eligible studies. Statistical analyses were performed in R software (version 4.4.0) using the “meta” package. Results: Four RCTs involving 701 patients were included, with 351 patients in the intervention group and 350 in the control group. Patients’ ages ranged from 18 to 78 years, with 51.4% male and 48.6% female. Cytogenetic risk in the intervention group was 4.7% favorable, 74.4% intermediate, and 4.7% adverse; in the control group, these rates were 2.5%, 65.9%, and 4.7%, respectively. FLT3i maintenance significantly reduced pooled relapse risk (HR 0.50, 95% CI: 0.34–0.74) and pooled mortality (HR 0.63, 95% CI: 0.44–0.91) at a median follow up of 24 months from allo-HCT. Hematologic toxicity was higher in the FLT3i group (RR 2.12, 95% CI: 1.67–2.70), as was chronic GVHD (RR 1.18, 95% CI: 1.00–1.41). Acute GVHD (RR 1.05, 95% CI: 0.78–1.41) and hepatotoxicity (RR 1.09, 95% CI: 0.72–1.66) rates were similar, while skin toxicity was less frequent in the FLT3i group (RR 0.36, 95% CI: 0.16–0.84). Conclusions: Our analysis suggests that FLT3i maintenance post-allo-HCT improves RFS and OS in FLT3-ITD-mutated AML patients compared to SOC but is associated with increased hematologic toxicity and chronic GVHD. Future clinical trials should evaluate the benefit of FLT3i maintenance post alloHCT based on MRD status assessed by next generation sequencing (NGS) based assays. Outcomes reported by the included studies. Type of FLT3-i Relapse free survival at 24 months Overall Survival at 24 months HR (95% CI) P-value HR (95% CI) P-value Levis et al. Giltetrinib 0.679(0.459-1.005) 0.52 0.846(0.554-1.293) 0.44 Burchert et al. Sorafenib 0.39(0.18-0.85) 0.01 0.516(0.239-1.112) 0.85 Maziarz et al. Midostaurin 0.60(0.17-2.14) 0.42 0.58(0.19-1.79) 0.34 Xuan et al. Sorafenib 0.37(0.22-0.63) <0.0001 0.48(0.27-0.86) 0.01 Pooled Hazard Ratio (95% CI) 0.50 (0.34-0.74) 0.63 (0.44-0.91)

This article highlights herpes zoster radiculitis, a condition that predominantly affects elderly patients and classically presents with progressive limb weakness, pain, and vesicular rash. Neuroimaging with MRI may demonstrate nerve root enlargement with T2-hyperintensity and gadolinium enhancement. Diagnosis can be confirmed with varicella zoster virus PCR in CSF. Effective treatment includes IV acyclovir and neuropathic pain agents such as gabapentin, which together can lead to symptomatic improvement. Early diagnosis and comprehensive treatment are crucial to prevent complications. Patients with zoster-associated plexopathy have a higher incidence of postherpetic neuralgia compared to those with herpes zoster rash alone. Thus, multimodal treatment involving antivirals, rehabilitation, and pain management is essential for recovery.

ABSTRACT Pneumonia may be caused by a diverse group of microorganisms; however, a microbiologic diagnosis is not universally made. Molecular tests such as the BIOFIRE FILMARRAY Pneumonia Panel (BF-PP) offer the possibility of rapid identification of potential pneumonia pathogens. This retrospective analysis was conducted as a sub-study of a recently published randomized controlled trial. Specimens from patients with suspected pneumonia were tested by the BF-PP, with results compared to cultures. The overall BF-PP positivity rate was 44.8% (252/563), and was higher [64.6% (164/254)] in specimens from patients ultimately diagnosed with pneumonia. Discrepancies between the BF-PP and cultures were most common for Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis, and Streptococcus agalactiae . Positive percent agreement (PPA) and negative percent agreement (NPA) between the BF-PP and culture were 91.4% (CI 86.3%–94.9%) and 83.6% (CI 79.5%–87.2%), respectively. For most bacteria, a correlation between high genomic abundance (genomic copies/mL) reported from the BF-PP and culture growth abundance was found. In specimens from patients ultimately diagnosed with pneumonia, clinical consistency—assessed based on whether BF-PP results aligned with associated culture results—was 79.9% and was highest for bronchoalveolar lavage fluid specimens. The BF-PP has reliable analytical performance and offers the potential advantage over conventional cultures of providing higher detection rates and more rapid results. Interestingly, despite the use of this advanced molecular diagnostic tool, one-third of pneumonia cases remained without a microbiologic etiology. IMPORTANCE This study evaluates the BIOFIRE FILMARRAY Pneumonia Panel by comparing its performance to conventional cultures in a real-world patient population (including patients ultimately diagnosed as not having pneumonia) using different types of specimens. Findings show a higher detection rate of microorganisms with the panel compared to cultures, suggesting that this test could aid in tailoring treatments for pneumonia. However, challenges remain and require further study, including distinguishing true pathogens from colonizing microorganisms and determinig why one-third of patients diagnosed with pneumonia still lacked a microbiologic etiology.