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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: Angina with no obstructive coronary arteries (ANOCA) is clinically challenging to diagnose and manage. The agreement between Doppler-derived coronary flow reserve (CFR Doppl ) and PET-derived CFR (CFR PET ) in patients with ANOCA remains unclear. Aims: To evaluate the correlation between Doppler- and PET-derived CFR in patients with ANOCA. Methods: We conducted a single-center, retrospective study of adult patients (age ≥18 years) with ANOCA who were referred for evaluation of possible microvascular ischemia with Doppler- and PET-derived CFR at the Mayo Clinic (Rochester, MN) between January 1, 2018, and May 1, 2024. Pearson correlation was used to quantify the association between Doppler- and PET-derived CFR. Agreement between Doppler- and PET-derived CFR was assessed by Bland-Altman analysis using a 2-way mixed effects model with measures of absolute agreement. Results: A total of 66 patients were initially identified, of which 40 were included in the final analysis (66.7% female, median age 58 years [Q1-Q3: 45-66 years]). Median time between PET- and Doppler-derived CFR was 8 days (Q1-Q3: 1-31 days). Median CFR Doppl was 2.75 (IQR: 2.23-3.28) and median CFR PET was 2.50 (IQR: 2.10-3.10). Doppler-derived CFR displayed a wider range than PET-derived CFR (0.8-5.2 vs 1.2-4.0). A strong correlation was found between Doppler- and PET-derived CFR ( r= 0.81; p<0.001). The corresponding Bland-Altman plot showed an overall bias of 0.27±0.56 (intraclass coefficient=0.85; p<0.001). Conclusions: While invasive coronary angiography with CFR Doppl is the gold-standard for the diagnostic evaluation of ANOCA, PET imaging with CFR PET offers an excellent first line non-invasive modality for diagnosis of coronary microvascular dysfunction.

Introduction: Metabolic pharmacotherapies [Glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter type 2 inhibitors (SGLT2i)] have shown benefit in patients with heart failure and preserved ejection fraction (HFpEF). It remains unclear whether the two classes would have additive effects. Methods: We performed a retrospective study using a de-identified federated database with 89 contributing health care organizations (HCO), including over 126 million patients (TriNetX Research Network, Cambridge, MA; date of data access: May 23, 2024). TriNetX regularly aggregates clinical data directly from participating HCOs, and performs extensive data quality and accuracy assessment. While TriNetX obfuscates institutional information relating to participating HCOs, a typical HCO includes a large academic health center with inpatient, outpatient, and specialty care services. We identified all patients with a diagnosis of Heart failure with preserved ejection fraction (HFpEF, ICD-10: I50.3), and SGLT2i usage. We then categorized this patient population into two cohorts, including patients with concomitant GLP1RA use, and patients without GLP1RA use. For both cohorts, we collected data on patient demographics, and the outcomes of all-cause mortality, and all-cause hospitalization, occurring up to 10-years after the index diagnosis. We evaluated differences in outcome risk using hazards ratios and 95% confidence intervals. Results: Prior to propensity score matching, we identified 114,329 patients, with 7931 patients receiving SGLT2i +GLP1RA vs 106398 receiving SGLT2i-alone. Majority (55.7%) identified as white and 24.4% as African Americans and >90% of the patients had a diagnosis of type 2 diabetes mellitus. After propensity matching, the rate of all-cause hospitalization within the combination group was lower than SGLT2i group (29.6% vs 32.4%, HR 0.76 [0.73- 0.79], P<0.001). All-cause mortality for the combination group was 6.8% versus 10.6% within the SGLT2i-alone group (HR 0.52 [0.47-0.56], P<0.001)). Conclusion: In this propensity-matched cohort, patients with HFpEF receiving GLP1RA and SGLT2i had lower rates of hospitalizations and all-cause mortality compared with those receiving SGLT2i alone. Large randomized controlled trials are warranted to corroborate these findings.

Background: Coronary in-stent restenosis (ISR) secondary to neointimal hyperplasia or neoatherosclerosis remains a significant challenge following percutaneous coronary interventions (PCI), with no consensus on the optimal revascularization strategy. We compared the outcome of PCI for ISR using drug-coated balloons (DCB) and drug-eluting stents (DES) and investigated the time trends in their clinical outcomes. Methods: PubMed, Embase, Scopus, and the Cochrane Library databases were searched through May 2024. We included randomized controlled trials (RCTs) comparing DCB versus DES among patients with coronary ISR. The primary outcome was target lesion revascularization (TLR). Secondary outcomes included all-cause mortality, myocardial infarction (MI), stent thrombosis, and late lumen loss (LLL). Random-effects models were employed to analyze outcomes within 1-year and beyond 1-year intervals. Meta-regression analysis was used to investigate the effect of age, sex, history of diabetes, hypertension, dyslipidemia, smoking, and ejection fraction on all outcomes by applying mixed-effect models. Results: We included 10 RCTs (1034 patients in the DCB group and 943 patients in the DES group). We found similar incidence of 1-year TLR (odds ratio [OR] 1.36; 95% confidence interval [CI] 0.86, 2.14; P 0.194; I 2 43.3%) and >1-year TLR (OR 0.94; 95% CI 0.57, 1.56; P 0.817; I 2 0%) with the use of DCB versus DES. The risks of all-cause mortality, MI, and stent thrombosis were comparable between DCB and DES in 1-year and beyond 1-year follow-ups. At 6-9 months angiographic follow-up, DCB was associated with non-significantly lower LLL compared to DES (standardized mean difference [SMD] -0.12 millimeters; 95% CI -0.29, 0.05; P 0.170; I 2 71.7%). Meta-regression indicated that higher prevalence of diabetes was associated with an increased risk of 1-year revascularization after DCB compared to DES (Estimate 0.07; P 0.003; I 2 0%). Additionally, male sex was associated with an increased LLL in DCB versus DES (Estimate 0.034; P 0.001; I 2 41.8%). No association was found between other baseline characteristics and measured clinical outcomes. Conclusion: DCB demonstrated comparable PCI outcomes compared to DES in patients with coronary ISR.

Introduction: Metabolic equivalents (METs), a measure of energy use during a specified exercise intensity, and volume of oxygen consumed (VO2) are key measurements in cardiopulmonary exercise tests (CPETs). METs are traditionally converted to VO2 via multiplying METs by 3.5 ml/kg/min when VO2 data is not available, due to the fact that the latter requires more-expensive, accurate measurements of volume of inspired and expired oxygen and CO2. However, it is unclear which populations have significant variation between peak METs and peak VO2. Research Question: In a general cardiology population, do older women have a weaker relationship between peak METs and peak VO2? Methods: We present a retrospective study analyzing the relationship of peak METs and peak VO2 achieved on a CPET. Patients presenting to the cardiology clinic who received a CPET from 2017-2022 were included. Patients with severe valvular dysfunction, congenital heart disease, prior coronary artery bypass grafting, or ejection fraction < 50% were removed to limit confounding. A Spearman correlation coefficient was calculated for the whole sample comparing peak METs and peak VO2. Subsequently, a subgroup of women age 65 or greater were compared to the general sample by a fisher’s z transformation. Results: 1907 patients were included. There was a strong positive correlation between peak VO2 and peak METs in the whole sample (r(1860) = 0.914), p<0,001), shown in Figure 1. Women age 65 or greater had a weaker correlation (r(190)=0.808, p<0.0001) compared to the those who were not (r(1668) = 0.915, p<0.0001; z = -5.656, p<0.001), shown in Figure 2. Conclusions: Peak METs and peak VO2 have an extremely strong positive correlation in a general cardiology population. However, these relationships weaken for women age 65 or greater. METs are an accurate, cost-effective proxy measurement of VO2 in a general population, however may lack reliability for certain demographics.

Background: Coronary microvascular disease (CMD) may be endothelium-independent (coronary flow reserve, CFR<2.5) or endothelium-dependent (<50% increase in coronary blood flow in response to acetylcholine). Endothelium-independent CMD has been subclassified into structural and functional groups based on hyperemic microvascular resistance (hMR, mmHg/cm/s). We hypothesized that endothelium-dependent CMD also has these subtypes. Methods: Patients with non-obstructive coronary artery disease who underwent coronary catheterization of the left anterior descending artery were included (n=112). Pressure and flow were recorded at rest, with adenosine, and with acetylcholine. Patients were classified by endothelial type and functional CMD (hMR<2.5) or structural CMD (hMR>2.5). Wave intensity analysis was performed and cumulative separated wave intensity (Joules/m 2 ) was calculated by standard formulae. Three dominant waves were analyzed (forward compression wave, FCW; backward compression wave, BCW; backward expansion wave, BEW). Results: Seventy-four of 109 patients had CMD, of which 59 had endothelium-independent and 38 had endothelium-dependent CMD (23 had both). Functional and structural subgroups were identified (Figure 1). All CMD subtypes had significantly different wave intensities at rest, adenosine, and acetylcholine (p<0.05). Comparing subtypes, there was no difference in wave intensities at rest. However, wave intensities significantly differed between all CMD subtypes with adenosine and acetylcholine, with higher energy waves in the endothelium-independent and functional groups (p<0.05, Figure 2). Conclusions: CMD is a heterogenous condition with distinct subtypes. Functional and structural groups exist in both endothelium-dependent and endothelium-independent CMD. These subgroups have distinct hemodynamic profiles as measured by wave intensity. A patient-specific approach to first line medical therapy may be improved by subgroup classification.

Background: About one in five adults at age 40 will develop heart failure (HF) during their lifetime. Risk factors for HF (e.g., hypertension, etc.) alter cardiomyocytes structure and function resulting in HF. At the cellular level, these changes consist of mis/over-expression of genes that regulate cardiac identity (e.g., CamK2d, PKC, etc). The current paradigm for treating HF is pharmacological intervention or surgery; however, with few exceptions, the condition worsens with time. We are proposing a paradigm-shift for treating HF from a drug-centric system to a molecular approach that would reverse hypertrophy and adverse remodeling. Methods: A cardiac targeting peptide (CTP) was generated and linked by disulfide bond to miRNA106a, which was then introduced into a HF mouse model to measure its ability to reverse multiple heart failure parameters. CTP-miRNA106a was also introduced into a human cardiac cell line, followed by multiple analyses including Western Blot, qPCR, FACS, immunofluorescence all used to identify mechanism(s) utilized by CTP-miRNA106a to reverse HF characteristics. Results: Bio-distribution studies showed CTP delivered its miRNA106a cargo specifically to the heart within 30 mins, followed by clearance of CTP from the heart to the kidneys and liver by 3-5hrs post systemic drug injection. MiRNA106a persisted in cardiomyocytes until day 7 (latest tested time-point). CTP-miRNA106a reversed Ang2/Iso induced hypertrophy in 90% of the experimental mice ( Fig1 ). We also identified two potential HF intracellular signaling mechanisms (PLCb1/PKC/IP3 and NfkB) targeted by CTP-miRNA106a that could benefit both types of HF, HFrEF and HFpEF. PLCβ1 is a direct target for miRNA106a while the Nfkb pathway is indirectly targeted by decreased Camk2d (an miRNA106a target) signaling to IκBα. NfkB activity is quelled by miRNA106a. Conclusions: Our approach utilizes the function of miRNA106a to downregulate genes involved in cardiac hypertrophy and inflammation through the PLCb1 and CamKIId/Nfkb pathways. Most importantly, using a CTP-miRNA106a, we show delivery of miRNA106a cargo is specific to cardiomyocytes both in vitro and in vivo and that once delivered, many HF parameters including hypertrophy are reversed.

Abstract Brain tumors constitute significant morbidity and mortality in sub-Saharan Africa (SSA). There is no previous large-scale effort focusing on brain tumor genetics in SSA. This project aims to map out the current neuro-oncology capacity in terms of workforce and available services in SSA. This is an ongoing online survey among a cross section of neuro-oncology practitioners spread across SSA countries to capture information on the distribution, number of available neuro-oncology care practitioners, capacity for neuropathology and molecular diagnosis, management of brain tumors, cancer registration, and tumor biobanking. The survey was disseminated by the Society for Neuro-oncology in SSA (SNOSSA). There were 83 respondents representing 15 countries and 52 health institutions: 46 tertiary, 4 secondary, 1 private and 1 other. Here, we present data on the 52 institutions. The prevalence of specialties was 87% neurosurgery, 75% anatomic pathology, 69% medical oncology, 64% neurology, 60% radiation oncology, and 39% neuropathology. For radiologic evaluation, 81% of institutions were reported to have both CT and MRI, 17% CT only, and one institution neither. For molecular testing, 46% have access to IHC or NGS testing, whereas 52% were reported to have neither. A neuro-oncology tumor board was reported at 58% of institutions. A general cancer registry is available in 64% of institutions, 31% have a brain tumor specific registry and 10% have a brain tumor biorepository. This study shows that SSA has substantial potential in neuro-oncology care practice capacity and facilities. Most significant gaps remain in areas such as neuropathology and molecular testing, which makes widespread implementation of the WHO 2021 diagnosis challenging. Understanding the prevalence of CNS tumor subtypes is also difficult due to low number of brain tumor registries and biobanks in SSA. The present findings reveal strategic opportunities, especially in neuropathology, tumor registries, biobanks, and infrastructure for IHC and NGS in SSA.

PURPOSE The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND. METHODS The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.gov identifier: NCT06464341 ) retrospectively analyzed data from patients with stage I to III breast cancer with ITCs in SLNs after NAC from 62 centers in 18 countries. The primary end point was the 3-year rate of any axillary recurrence. The rate of any invasive recurrence was the secondary end point. RESULTS In total, 583 patients were included, of whom 182 (31%) had completion ALND and 401 (69%) did not. The median age was 48 years. Most patients (74%) were clinically node-positive at diagnosis and 41% had hormone receptor–positive/human epidermal growth factor receptor 2–negative tumors. The mean number of SLNs with ITCs was 1.2. Patients treated with ALND were more likely to present with cN2/3 disease (17% v 7%, P < .001), have ITCs detected on frozen section (62% v 8%, P < .001), have lymphovascular invasion (38% v 24%, P < .001), and receive adjuvant chest wall (89% v 78%, P = .024) and nodal radiation (82% v 75%, P = .038). Additional positive nodes were found at ALND in 30% of patients, but only 5% had macrometastases. The 3-year rates of any axillary and any invasive recurrence were 2% (95% CI, 0.95 to 3.6) and 11% (95% CI, 8 to 14), respectively, with no statistical difference by type of axillary surgery. CONCLUSION The nodal burden in patients with ypN0(i+) was low, and axillary recurrence after ALND omission was rare in patients selected for this approach. These results do not support routine ALND in all patients with ypN0(i+).