Citations

Investment in physical space is a key strategic decision for healthcare managers. Understanding the current utilisation of clinical space is a significant input for this decision. Historically, direct observation or analysis of electronic health record (EHR) timestamps has been used to assess ambulatory space utilisation. Manual observation is prohibitively expensive, prospective and infeasible for large spaces. EHR data is limited to electronically captured workflows and to the quality of data capture. Two pilots explored the efficacy of real-time location systems (RTLS) to assess outpatient space utilisation to assist healthcare management professionals to make space allocation decisions. RTLS was shown to be viable, with accuracy that was not different from EHR-derived utilisation. RTLS had the following benefits: (a) more granular information, (b) data coverage in areas without EHR timestamps and (c) real-time assessment of utilisation. RTLS is an option for ambulatory care managers to understand the needed space for clinical operations.

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have become increasingly utilized in patients undergoing percutaneous coronary intervention (PCI). Despite these purported advantages, prior reports regarding the use of IVUS and OCT have indicated that contemporary use of intravascular imaging remains low with significant regional variation. Here, we present the findings of an updated contemporary analysis regarding the use of IVUS/OCT-guided PCI versus angiography-guided PCI in the United States. We also evaluated in-hospital mortality and clinical outcomes between IVUS/OCT-guided PCI versus angiography-guided PCI-only over million patients in the United States. There has been a significant decrease in the number of PCIs performed, while there has been increasing in the trend of IVUS/OCT-guided PCI over this period. Most importantly, we found that IVUS/OCT-guided PCI was associated with better clinical outcomes in terms of in-hospital mortality, compared with angiography-guided PCI.

Abstract BACKGROUND Recurrent anaplastic astrocytoma (AA), a grade 3 brain cancer, remains an unmet medical need. STELLAR was a phase III randomized, open-label trial of eflornithine (ornithine decarboxylase inhibitor) with lomustine versus lomustine alone, originally for patients with recurrent AA. However, as the WHO definition of AA evolved during trial conduct (e.g., excluding IDH wild-type disease), we determined results in both the original ITT population and by revised molecularly defined WHO 2021 diagnoses in pre-planned analyses. METHOD Key eligibility: age ≥ 18, AA (2016 WHO criteria), first recurrence ≥ 6 months after radiation and temozolomide, KPS ≥ 70, no imaging findings consistent with grade 4 glioblastoma. Stratification: IDH, age, resection extent, and geography. Patients were randomized to Arm A: eflornithine (2.8 g/m2 TID Q 2/3 weeks) with lomustine (90 mg/m2 Q 6 weeks) or Arm B: lomustine (110 mg/m2 Q 6 weeks). Primary endpoint was OS. The pre-specified hazard ratio (HR) goal was 0.667 based on projected median OS (mOS) increase to 18 months from 12 months. RESULTS 343 pts (172/171 Arms A/B) were randomized (105 sites, 8 countries). ITT analysis found no difference between arms (mOS 23.4 vs. 20.3 months, HR = 0.94). However, a pre-specified subset analysis in IDH mutant, 2021 WHO-defined grade 3 astrocytoma (n=194), showed significant improvement with eflornithine (mOS 34.9 vs. 23.5 months, HR = 0.64, log rank p = 0.016) and PFS (15.8 vs. 7.2 months, HR = 0.58, log rank p = 0.015). No difference was observed in the IDH wild-type subset. AEs were consistent with historic data. CONCLUSION There was no difference in OS between arms in the ITT analysis. However, medically meaningful and statistically significant OS and PFS benefits were observed with eflornithine in the pre-planned analysis of patients with molecularly defined 2021 WHO CNS grade 3 astrocytoma.

Abstract GBM AGILE(NCT03970447) is a phase 2/3 Bayesian adaptive registration platform trial testing multiple therapies against a common control. Paxalisib, a PI3K/mTOR inhibitor, is the 3rd arm in the trial to conclude evaluation. METHODS Paxalisib was open to patients with newly diagnosed unmethylated (NDU) and recurrent (RD) glioblastoma, with three possible signatures: NDU, RD, and All(NDU+RD). Arm enrollment occurred Dec2020 through May2022. Control patients were enrolled from study initiation (July2019) and were treated with temozolomide(NDU) or lomustine(RD). GBM AGILE investigational arms have 1 or 2 stages, with adaptive randomization in stage 1 and fixed randomization if arms continue to stage 2. Efficacy is based on OS hazard ratio(HR) of Arm/Control. Efficacy goal is final Bayesian probability ≥ 98% for HR<1.00 in combined Stages. An Arm continues to Stage 2 if Bayesian predictive power (PP) ≥ 0.8. An Arm stops accruing in Stage 1 if it reaches maximal sample size(N) or does not meet a minimum efficacy threshold (PP<0.25 for all signatures when N>50). Clinical cut-off is 12 months after accrual stops. The maximum N for paxalisib was approximately 150(Stage 1) and 50(Stage 2). RESULTS After paxalisib reached >150 patients in Stage 1, accrual stopped [Paxalisib/control N 54/75(NDU), 100/188(RD)]. Neither PP thresholds for moving to Stage 2 nor stopping for minimum efficacy were met. Following an unplanned public disclosure that the arm did not continue to stage 2, clinical cut-off for final analysis (planned May2023) was updated to public disclosure date (August2022). At final analysis mean HRs were 0.89(NDU), 1.25(RD), 1.05(All), probabilities of HR<1.00 of 0.72(NDU), 0.076(RD), 0.398(All). Model estimated median OS paxalisib/control (months) were 14.77/13.84(NDU) and 8.58/10.06(RD). CONCLUSION Paxalisib did not show survival benefit over cumulative control in final primary analysis; additional secondary analyses are being considered. GBM AGILE continues to rapidly and efficiently assess therapies in ND and RD glioblastoma.

Abstract Background Glioblastoma (GBM) has a median survival of <2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance. We added pexidartinib to standard-of-care RT/temozolomide (TMZ) in patients with newly diagnosed GBM to assess the therapeutic benefit of altering the tumor microenvironment with pexidartinib. Methods In this open-label, dose-escalation, multicenter, Phase 1b/2 trial, pexidartinib was administered in combination with RT/TMZ followed by adjuvant pexidartinib + TMZ. During Phase 1b, pexidartinib was given 5 or 7 days/week at multiple dosing levels. The primary Phase 1b endpoint was the recommended Phase 2 dose (RP2D). Phase 2 patients received the RP2D with the primary endpoint of median progression-free survival (mPFS). Secondary objectives were median overall survival (mOS), pharmacokinetics, and safety. Results The RP2D of pexidartinib was 800 mg/day for 5 days/week during RT/TMZ, followed by 800 mg/day for 7 days/week with adjuvant TMZ. mPFS was 6.7 months (90% CI: 4.5, 11.5) for the modified intention-to-treat population. The actual mOS was 13.1 months (90% CI: 11.5, 24.5), and the mOS corrected for comparison with matched historical controls was 18.8 months (95% CI: 12.6, 28.0). Conclusions This trial established the RP2D of pexidartinib in combination with RT/TMZ and adjuvant TMZ. Pexidartinib was generally safe and well tolerated. Although the study regimen with pexidartinib was not efficacious, pharmacodynamic studies showed modulation of systemic markers that could lead to alteration of the tumor microenvironment.

SummaryTo assess the relevance of co‐occurring somatic mutations in TP53‐mutated myeloid neoplasms with ≥10% blasts, we pooled 325 individuals from 10 centres. We focused on comparing three published somatic co‐alteration signatures comprising (1) nine MDS‐related genes (‘ICC‐MDSR’), (2) ICC‐MDSR + additional secondary mutations‐related genes (‘Tazi signature’) and (3) EPI6 (comprising six genes). Outcomes examined were 24‐month overall survival (OS24) and front‐line complete response (CR1). The median age was 69 years with 77% receiving front‐line hypomethylating agents (HMA). All three signatures ICC‐MDSR (p = 0.009), Tazi signature (p = 0.001) and EPI6 (p = 0.025) predicted inferior CR1. In the low‐intensity (HMA) subgroup, only Tazi signature (p = 0.026) predicted inferior CR1. In OS24 analysis of the HMA‐treated subgroup (N = 200), only Tazi signature was adverse (hazard ratio, HR = 1.6 [1.1–2.2]; p = 0.011). However, a forward stepwise multivariable age‐adjusted Cox model including all three signatures picked EPI6 as the sole significant adverse predictor in the entire cohort (p = 0.0001) as well as within the HMA‐treated subgroup (p = 0.0071). These data confirm the value of testing co‐occurring somatic alterations even within a high‐grade TP53‐mutated myeloid neoplasm cohort.

Abstract Background Brain tumors represent a significant global health challenge, with rising incidence and mortality impacting individuals worldwide and contributing to cancer-related morbidity and mortality. In Africa, this burden is exacerbated by limited access to advanced diagnostics, treatment options, and multidisciplinary care, compounded by the absence of standardized cancer registration and tumor biobanking. The introduction of molecular diagnostics, as outlined in the 2021 World Health Organization central nervous system (CNS) tumor classification, adds complexity to brain tumor management, particularly in regions with scarce resources. Methods To address these issues, the Brain Tumor Consortium for Africa (BTCA) was established in 2023, bringing together experts to improve CNS tumor diagnosis, patient care, and research. The initial project, conducted via an electronic questionnaire, aimed to assess neuro-oncology capacity across Sub-Saharan Africa. Results The study revealed significant gaps, with a limited number of institutions incorporating molecular subtyping into their diagnostic algorithms. The consortium’s efforts focus on enhancing local data use, informing public policy, and promoting collaboration to advance neuro-oncology practices in Africa. By fostering a network enlisting the expertise of collaborators in the fields of neurosurgery, neurology, neuropathology, anatomic pathology, and medical and radiation oncology, the BTCA seeks to improve brain tumor management through better diagnostics, infrastructure, and policy advocacy. Future directions include expanding molecular diagnostic capabilities, standardizing brain tumor biobanking, enhancing data collection, and advocating for improved brain tumor care in national health agendas. Conclusions The BTCA represents a pioneering model of collaboration and innovation in addressing the unique challenges of brain tumor care in Africa.

Background: There is limited data on the safety and efficacy of ventricular tachycardia (VT) ablation in patients with chronic kidney disease (CKD). We examined the outcomes of patients with CKD undergoing VT ablation in a nationally representative cohort of patients. Methods: The National Inpatient Sample Database (NIS) was analyzed from 2018 to 2021 to identify patients ≥18 years old with VT undergoing ablation. Patients with atrial fibrillation, atrial flutter, supraventricular tachycardia, or pre-excitation syndrome were excluded. Patients were divided into those with CKD and without CKD. A multivariable logistic regression model was utilized to assess the association of CKD with in-hospital mortality and outcomes after adjusting for confounders. Results: Our cohort included 1608 VT ablation procedures, of which 428 (27%) were performed on CKD patients. Mean age was 63 (±13) years, 318 (19%) were female, and 1194 (74%) were White. 1475 (92%) of the procedures were done at an urban teaching hospital, and 1240 (77%) at a private non-profit hospital. On multivariable analysis, CKD was associated with significantly higher odds of death (adjusted odds ration [aOR]: 3.43; 95% confidence interval [CI]: 1.79-6.5; p=0.0002), acute decompensated heart failure (aOR: 3.1; 95% CI 2.24-4.56; p<.0001), bleeding (aOR: 1.53; 95% CI1.02-2.28; p<.03), and acute kidney injury (aOR: 4.49; 95% CI3.42-5.9; p<.0001). There was no difference in the odds of acute myocardial infarction, stroke, cardiogenic shock, vasopressor use, mechanical ventilation, and pericardial tamponade or pericardial procedures Figure . Conclusion: Patients with CKD undergoing VT ablation have an increased risk of mortality and adverse in-hospital outcomes when compared to patients without CKD. These hypothesis-generating findings need validation in future prospective studies for optimal pre-procedural risk stratification.

Background: Risk stratification for embolism in cardiac myxomas remains poorly explored. Goals: By this meta-analysis we studied the risk factors assicated with embolism among patients with cardiac myxoma. Methods: A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Google Scholar from their inception until January 2024. Statistical analyses were performed using Cochrane's RevMan 5.4 software. For each risk factor, the pooled odds ratio or mean difference was calculated along with the corresponding 95% confidence interval. Results: We included 18 studies in our analysis with a total population of 2601 out of which 525 patients (20.1%) had at least one episode of embolism. The pooled analyses showed that hypertension (p = 0.001), New York Heart Association I/II (p = 0.03), irregular tumor surface (p <0.00001), hyperlipidemia (p < 0.0001), coronary artery disease (p=0.01), high mean platelet volume (p=0.02), high tumor mobility (p<0.00001), were significantly associated with increased incidence of embolism. Female gender (p = 0.03) was the only risk factor associated with reduced risk. Other factors like smoking, atrial fibrillation, tumor size, age, body mass index (BMI), diabetes, left ventricular ejection fraction (LVEF), left atrial diameter (LAD) were not significantly associated with embolism (p > 0.05). Conclusion: Our study is the first to report significant pooled outcomes for gender, hyperlipidemia, coronary artery disease, mean platelet volume, and tumor mobility in the population discussed. Hypertension, New York Heart Association I/II, irregular tumor surface, hyperlipidemia, coronary artery disease, mean platelet volume and tumor mobility were significantly associated with high risk while female gender was associated with low risk of embolism. Patients with high-risk factors might benefit from early evaluation and definitive treatment (surgery).

Abstract The field of infectious diseases (ID) offers a rewarding career path and is widely viewed as an essential subspecialty in medicine. However, in recent years, these positive aspects have been overshadowed by concerns surrounding low fellowship match rates, undercompensation, and burnout. The Infectious Diseases Society of America Fellowship Training Program Directors Committee met in 2023, discussed the future of ID as a specialty, and sought to develop strategies to highlight the value and opportunities of ID for future generations, as well as underscore the importance of and provide tools for positive messaging to trainees about the subspecialty. This paper presents ideas generated at this meeting and is meant to serve as a reference for ID training program directors, as well as the wider ID community, in uplifting and shaping the future of the field.