Citations

Abstract Purpose: Colorectal Cancer (CRC) is a leading cause of death from cancer globally. Surgery is the mainstay of treatment for localized CRC; however, little is known about survival outcomes following CRC surgery in low- and middle-income countries (LMICs). In this study, we examine the published literature for data on long-term outcomes following CRC resections in LMICs. Methods: We systematically reviewed PubMed, Web of Science, Embase, and Global Index Medicus for original research articles reporting survival data after CRC resection with curative intent in LMICs, published between January 2005 and May 2022. LMICs were defined according to the 2020 World Bank categories. We excluded studies without English full text or involving pediatric populations (<18 years), non-primary colorectal, benign disease, and endoscopic/transanal resection only. Studies from China dominated the published literature and were excluded. Abstracts and full texts were reviewed by two independent reviewers, and a third reviewer resolved conflicts. Disease-free survival (DFS) and overall survival (OS) data were extracted, and random effects modelling was used to estimate the pooled survival rates. Results: Our search returned 32,261 articles. After deduplication, 20,729 abstracts were assessed for eligibility, with 154 articles meeting inclusion criteria, representing a total of 20,589 CRC patients. 98 (63.6%) studies were from upper-middle-income (UM) countries, 55 (35.7%) from lower-middle-income (LM) countries and only one was from a low-income (L) country. Notably, only 27 (20%) of the 137 LMICs were represented in the literature. Turkey accounted for the highest frequency (29%) of included articles. Most (60%) of the studies were retrospective cohort design, and only three (3) were randomized controlled trials. The pooled 5-year OS estimate was 88% (95% CI: 77–95) for Stage I disease, 76% (69–81) for Stage II, and 57% (49–64) for Stage III. 5-year DFS estimates were 82% (71–90), 76% (67–84), and 59% (51–65) for stages I, II and III respectively. Survival rates varied considerably between income groups, with the strongest disparity seen with Stage III OS data at 18 months: 89% in UM, 86% in LM, and 50% in L (p=0.0005). Conclusion: With the rising incidence of CRC in LMICs, our work highlights the dearth of data on long-term outcomes following CRC operations in LMICs and emphasizes the urgent need for research capacity building, especially in low-income countries. Citation Format: Oluwasegun Afolaranmi, Thomas M. Diehl, Sehar Salim Virani, Qiuyu Yang, Kenechukwu Okwunze, Adel H. Khan, Nabiha Akhlaq Mughal, Daniel Schroeder, Sheida Pourdashti, Leslie Christensen, Sadaf Khan, Syed Nabeel Zafar. Survival Following Colorectal Cancer Surgery in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 84.

Hypoplastic left heart syndrome (HLHS) is the most lethal congenital heart disease (CHD). The pathogenesis of HLHS is poorly understood, and due to the likely oligogenic complexity of the disease, definitive HLHS-causing genes have not yet been identified. Postulating impaired cardiomyocyte proliferation as a likely important contributing mechanism to HLHS pathogenesis, and we conducted a genome-wide siRNA screen to identify genes affecting proliferation of human iPSC-derived cardiomyocytes (hPSC-CMs). This yielded ribosomal protein (RP) genes as the most prominent class of effectors of CM proliferation. In parallel, whole genome sequencing and rare variant filtering of a cohort of 25 HLHS proband-parent trios with poor clinical outcome revealed enrichment of rare variants of RP genes. In addition, in a familial CHD case we identified a rare, predicted-damaging promoter variant affecting RPS15A that was shared between the HLHS proband and a distant relative with CHD. Functional testing with an integrated multi-model system approach reinforced the idea that RP genes are major regulators of cardiac growth and proliferation, thus potentially contributing to the hypoplastic phenotype observed in HLHS patients. Cardiac knockdown (KD) of RP genes with promoter or coding variants (RPS15A, RPS17, RPL26L1, RPL39, RPS15) reduced proliferation in generic hPSC-CMs and caused malformed hearts, heart-loss or even lethality in Drosophila. In zebrafish, diminished rps15a function caused reduced CM numbers, heart looping defects, or weakened contractility, while reduced rps17 or rpl39 function caused reduced ventricular size or systolic atrial dysfunction of the atrium, respectively. Importantly, genetic interactions between RPS15A and core cardiac transcription factors TBX5 in CMs, Drosocross, pannier and tinman in flies, and tbx5 and nkx2-7 (nkx2-5 paralog) in fish, support a specific role for RP genes in heart development. Furthermore, RPS15A KD-induced heart/CM proliferation defects were significantly attenuated by p53 KD in both hPSC-CMs and zebrafish, and by Hippo activation (YAP/yorkie overexpression) in developing fly hearts. Based on these findings, we conclude that RP genes play novel critical roles in cardiogenesis and constitute an emerging class of gene candidates likely involved in HLHS.

Background: Upper gastrointestinal bleeding (UGIB) is a common medical emergency associated with significant morbidity, mortality, and healthcare costs. Many patients undergo early endoscopy despite the absence of active bleeding. PillSense is a novel Food and Drug Administration (FDA)-cleared ingestible capsule that rapidly detects the presence of blood in the upper GI tract and may optimize triage decisions. Methods: We conducted a retrospective study evaluating the impact of PillSense on the management of suspected UGIB in an academic center. The primary outcome was the association between capsule results and clinical decision-making, including endoscopy deferral, prioritization, outpatient scheduling, and airway protection. Secondary outcomes included transfusion requirements, time-to-endoscopy, endoscopic intervention, and 30-day adverse events. Results: A total of 28 patients (mean age 64.4 ± 17.9 years, 82.7% male) were included. Compared with negative results, positive results were associated with higher transfusion requirements (median 3 (IQR 3–6) vs. 2 (IQR 1–3.25) units; p = 0.041) and shorter time-to-endoscopy (median 0.2 (IQR 0.01–1) vs. 2 (IQR 1–15.5) days; p = 0.017). In high-risk for sedated endoscopy patients, negative results were associated with EGD deferral in 53.8%, with no subsequent adverse events within 30 days. Endoscopic intervention was performed in 62.5% of positive-result patients versus 9.5% of negative-result patients. Conclusions: The PillSense results were associated with differences in triage and management of high-risk patients with suspected UGIB. Its rapid, accurate, and non-invasive results may reduce unnecessary urgent endoscopy procedures, improve resource utilization, and enhance patient safety, particularly in the highest-risk populations.

Abstract Background Historically, 25-hydroxyvitamin D (25OHD) assays have under- or over-recovered 25-hydroxyvitamin D2 (25OHD2), but assay manufacturers have modified their reagents to address this problem. In this study, we compared the second- and third-generation Roche assays as well as two contemporary offerings from Diasorin and Beckman against liquid chromatography–tandem mass spectrometry (LC-MS/MS). Methods We identified 50 remnant serum samples with 25OHD concentrations from across the analytical range of the second-generation Roche assay. To increase 25OHD2 representation, we identified 25 additional samples from individuals prescribed high-dose vitamin D2 supplements. We tested samples on Roche assays and circulated to laboratories performing Beckman and Diasorin 25OHD assays. We tested samples by LC-MS/MS to obtain concentrations for 25OHD2 and 25-hydroxyvitamin D3. Results Mean overall bias for each assay was 5.1 ng/mL or less against the LC-MS/MS measurement; mean proportional bias was 8.7% to 12.1%. Some individual specimens had much larger bias. 25OHD2 was under-recovered on average, but the bias for the third-generation Roche assay represents a significant improvement over the previous assay, and mean bias for current generation assays was no worse than −3.2 ng/mL. In most cases, clinical classification by automated assay values agreed with clinical classification by LC-MS/MS; where present, disagreements occurred near classification thresholds. Conclusions Automated 25OHD assays continue to improve, and 25OHD2 recovery no longer appears to be a significant concern for the assays evaluated here. All assays evaluated were adequate for clinical classification of vitamin D nutritional status and are suitable for routine use, including in patients prescribed high-dose vitamin D2.

Background: Discovering risk biomarkers in small benign breast disease (BBD) biopsies is constrained by scarce tissue and microanatomic heterogeneity of terminal duct lobular units (TDLUs). We tested whether tissue-sparing tissue microarray (TMA)–based Digital Spatial Profiling (DSP) can deliver reproducible, biologically coherent protein measurements across benign lobules and breast cancers (BCs), and how well DSP aligns with standard immunoassays. Methods: We performed a pilot using tissues from the Mayo Clinic BBD cohort using TMAs representing four contexts: terminal duct lobular units (TDLUs) from BBD biopsies preceding BC and matched BBD-controls, subsequent BCs, and BC-associated TDLUs. We profiled 79 proteins by DSP (37 retained after QC) and benchmarked against chromogenic IHC and OPAL immunofluorescence. Reproducibility was evaluated using intraclass correlation coefficients (ICCs), cross-platform agreement (weighted kappa), marker correlations, and mixed-effects models with false-discovery-rate (FDR) control. Results: We analyzed 368 BBD-TDLU cores (88 cases; 88 controls), 204 BC cores and 110 BC-associated TDLU cores. ICCs were highest in BC tissues, and lower in BC-associated TDLUs and BBD-TDLUs. Agreement was slight–to-fair in TDLUs but moderate (ER/PR) to substantial (BCL2) in BC. DSP recapitulated expected immunologic correlations (CD45 with T-cell, B-cell, and macrophage markers) and tissue-type gradients (BC > BC-associated TDLUs > BBD-TDLUs). Exploratory case–control differences in BBD-TDLUs did not persist after FDR control. Conclusions: TMA-based DSP is feasible in archival breast tissues and yields biologically coherent, cross-platform-benchmarked profiles that are particularly robust in BC, while conserving scarce TDLUS and clarifying current limits of single-marker risk stratification from benign lobules. These data provide a foundation for refined sampling and expanded panels in future TDLU-focused studies.