Publications

OBJECTIVE: To determine the effect of surgical and conservative treatment of adenotonsillar hypertrophy on right ventricular functions in children.

METHODS: An interventional study was conducted in 50 children with a mean age of 8.72 ± 4.72 years and 7.32 ± 3.84 years and randomized in medical and surgical groups. Cardiac parameters were observed at the time of enrollment, first month, third month, and sixth month after medical or surgical intervention.

RESULTS: The patients in the medical group did not show any resolution of symptoms at the end of the third month, while 36% of patients had resolution of symptoms at the end of the sixth month. Patients of this group had improvement only in right ventricular outflow tract systolic excursion at the end of the final follow-up. However, the surgical group found 88% of patients with complete resolution of symptoms at the end of the sixth month. The echocardiographic parameters of both the groups had improvements in the number of cardiac parameters like tricuspid annular plane systolic excursion, right ventricular outflow tract systolic excursion, pulmonary artery pressure, and pulmonary flow acceleration time at the end of the final follow-up (6 months); however, the inter-group analysis found significant improvement in the surgical group compared to the medical group.

CONCLUSION: Adenotonsillar hypertrophy is known to affect right ventricular functions, and these can be improved better with surgery than with conservative management. Hence, surgery should be prioritized in adenotonsillar hypertrophy to reduce the immediate or risks in adulthood of cardiovascular diseases in few selected patients.

Myocardial infarction results in irreversible cardiomyocyte loss and fibrotic remodeling in adult mammals, whereas some vertebrates retain the ability to regenerate cardiac tissue. Comparative studies suggest that immune responses critically influence repair outcomes, yet the immune programs associated with regeneration remain incompletely defined. Here, we investigate how immune modulation accelerates cardiac repair in the nonregenerative medaka (Oryzias latipes). Using bulk and single-cell transcriptomics combined with functional assays, we show that stimulation with the Toll-like receptor 3 agonist poly I:C accelerates early immune activation and enhances macrophage-dependent debris clearance, associated with inflammatory resolution after cardiac injury. Single-cell analysis of enriched myeloid populations identifies regeneration-associated macrophage subsets characterized by phagocytic and immune-regulatory gene programs, including elevated expression of granulin-a (grna). Spatial analysis by hybridization chain reaction reveals increased numbers of grna-expressing macrophages in the injury border zone, coinciding with the regenerative niche of cardiomyocyte proliferation. Consistent with these findings, administration of recombinant Granulin A enhances cardiomyocyte proliferation and reduces scar burden in medaka hearts. Together, these findings indicate that immune modulation reshapes macrophage functional states during cardiac repair and link macrophage-associated granulin expression to regenerative outcomes, highlighting macrophage properties as a potential target for improving heart repair.

OBJECTIVE: We investigated the extent of cellular, transcriptional, and translational activation throughout the liver following radiofrequency ablation (RFA).

MATERIALS AND METHODS: RFA of the healthy liver was performed in two 8-10-week-old male C57/Bl6 mice, no/sham procedure in one. One and 7 days after, single-cell RNA sequencing (scRNAseq) was performed on distant, untreated liver to examine > 6,000 genes from normalized datasets of > 6,000 cells/sample, enabling identification of ten major cell populations. We defined cell-to-cell interactions by CellphoneDB and identified active pathways via STRING-db analysis with Markov clustering. Twelve distant liver lobe samples were homogenized on day 3 or day 6 after RFA/sham procedure for SomaLogic proteomic analysis (> 1,300 genes), subsequent STRING-db analysis, and assessment of cellular origin (PanglaoDB-2021).

RESULTS: CellphoneDB identified crosstalk among all ten populations with 4,658 and 4,218 receptor/ligand pairs, identified on day 1 and day 7 post-RFA, respectively. On day 1, 360 differentially expressed genes were identified; on day 7, 430. Activated genes distributed into 16 clusters, including 66 chemokines/cytokines, including Ccl2 and Ccl7; 57 immunomodulators, including Il6, Ctla4 and Pdcd1; and 54 growth factors, including Vegf, Hgf, Pdgf, and Fgf. Angiogenesis pathway genes were observed in endothelial cells and hepatocytes. Pdcd1 and Ctla4 were notably increased transiently in T cells. Proteomic analysis included 228/443 genes (51%) identified by scRNAseq; 73/228 proteins (32%) demonstrated 25% elevation over controls. Overall, 427 proteins were elevated, with 9/10 cell populations contributing to increased protein expression (odds ratio 4.9‒7.0).

CONCLUSION: RFA diffusely activates cellular processes remotely from the ablation zone on both transcriptional and translational levels, altering tumorigenic and immunologic pathways simultaneously.

RELEVANCE STATEMENT: This study offers insights into liver tissue biology after RFA and provides a comprehensive picture of the molecular mechanisms put into motion by this procedure. A better understanding of these processes could provide a potential basis to develop specific biomarkers and effective adjuvant therapies following local tumor ablation.

KEY POINTS: RFA activates a multiplicity of hepatic cellular processes remotely from the ablation zone on a transcriptional and translational level. Single-cell RNA sequencing provides insights into widespread cellular origins of activated pro-immunogenic, pro-tumorigenic, and other pathways detected post-ablation. Consideration of the nature of this response may help achieve the clinical goals of adjuvant therapies and predictive biomarkers.

PURPOSE: To determine clinical and radiographic parameters predictive of interventions and adverse outcomes in patients with spontaneous rectus sheath hematoma.

METHODS: This retrospective, institutional review board approved study identified 261 patients with spontaneous rectus sheath hematoma from January 2000 to August 2021 through CT report searches. Demographics, clinical presentation, comorbidities, medications, and laboratory values were collected. CT scans were reviewed for hematoma characteristics including size, location, density, and active contrast extravasation. The primary outcome was the invasive intervention; and the secondary outcomes included transfusion requirements, length of hospital stay, acute kidney injury, readmission, and mortality. Categorical variables were compared using Fisher's exact test, while continuous variables were analyzed using Student's t-test or Mann-Whitney U test as appropriate based on normality assessment.

RESULTS: The cohort comprised 261 patients (median age 71 (IQR, 60-78) years, 59% female). Invasive treatments were performed in 41 patients (15.7%): 35 underwent angiography with embolization; 6 had surgical exploration. Invasive treatment was significantly more frequent among patients with trans-umbilical extension (25.7% vs 9.4%; p < 0.001), active contrast extravasation (46.7% vs 33.0%, p < 0.001), and hematoma volume > 443.5 cc (31.8% vs 9.6%, p < 0.001)." These patients had higher red blood cell transfusion requirements (85.4% vs. 47.7%, p < 0.001) and longer hospital stays (7 vs. 4 days, p < 0.001). The overall in-hospital mortality was 6.9%, with 1.9% attributable to rectus sheath hematoma.

CONCLUSION: While most rectus sheath hematomas are managed conservatively, specific CT findings-trans-umbilical extension, larger volume, and active contrast extravasation-predict invasive intervention and guide clinical decision-making.

The central principle of the theory of constraints is that in any complex system there are only a few constraints that limit the performance (ie, "throughput") of the system. These constraints are rate-limiting steps to throughput. Once the constraint or bottleneck is identified, resources are used to improve the utilization rate at the point of the constraint to make the process as productive as possible. Others in the organization also must work to maintain the high utilization rate at the constraint. Strategies such as buffers are used to increase throughput at the constraints. Although it was initially developed in manufacturing, the theory of constraints has been applied to many industries. By using the theory of constraints to evaluate the radiologic workflow, constraints can be identified through targeted process improvement projects for optimization at steps that affect the total throughput of the system. Constraints can be physical, such as equipment or space (eg, imaging units or recovery room beds), or related to personnel. Because radiology is currently in a resource-constrained environment, targeted interventions with highly effective processes could improve productivity or flow. Given the workforce shortages in radiology, determining whether the constraint is equipment- or personnel-related may lead to different improvement projects.

PURPOSE: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality in sub-Saharan Africa, with most cases arising from chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. Despite Rwanda's national hepatitis guidelines recommending biannual surveillance with abdominal ultrasound (US) and alpha-fetoprotein (AFP) testing, the extent of adherence remains unknown. This study aimed to assess adherence to HCC surveillance guidelines among HBV- and HCV-infected patients at a national referral hospital in Rwanda.

METHODS: We conducted a retrospective descriptive study of HBV- and HCV-infected patients attending the Rwanda Military Referral and Teaching Hospital between January 2022 and December 2024. Surveillance adherence was assessed based on the proportion of time covered by abdominal US and AFP testing, with coverage categorized as optimal (100%), intermediate (50%-99%), or poor (<50%).

RESULTS: Among 388 patients (mean age, 41.9 years; 73.4% male), 82.7% were HBV-infected. Over one third (31.4%) and nearly half (44.6%) of the patients never received an US or AFP test, respectively. Only 15.5% achieved optimal US coverage, and 12.1% had optimal AFP coverage. Surveillance coverage was worse in patients age 31-50 years and those residing in Kigali. Paradoxically, patients from rural provinces demonstrated better adherence. Thirteen patients (3.4%) had liver lesions detected on US, although lesion status was undocumented in 44.6% of cases.

CONCLUSION: Adherence to HCC surveillance guidelines in Rwanda is suboptimal, with significant gaps across age groups and regions. These findings underscore the need for integrating HCC surveillance into routine hepatitis care and leveraging Rwanda's decentralized health system to improve early cancer detection.

OBJECTIVE: To assess the impact of split-bolus (SB) single scan CT on the conspicuity of clear cell renal cell carcinoma (ccRCC) metastases compared with single-bolus injection.

METHODS: This retrospective cohort study included consecutive patients with histologically proven metastatic ccRCC who underwent both SB and single-bolus portal venous abdominal CT within 6 months between 2017 and 2022 in a single tertiary center. SB CT utilized BMI-adjusted contrast dose and kVp (80 to 120) with concurrent arterial and portal venous phases. Single bolus CT utilized BMI-adjusted contrast dose at 120 kVp at the portal venous phase. Wilcoxon rank test compared the conspicuity of metastases between the protocols.

RESULTS: Of the 47 patients, 80.9% were male, with a mean age of 67±10.4 years and a BMI of 27.1±5.7. There were 48 paired CTs performed with a median interval of 93 days. Contrast dose was 143±27 ml for SB and 108±26 ml for single-bolus (P<0.001). Sixty-six metastases were analyzed, with an average size of 2 cm: 48.5% in the pancreas, 28.8% in skeletal muscle, and 22.7% in the liver. The median contrast-to-noise ratio (CNR) was higher with SB compared with single-bolus for all metastases (3.0 vs. 1.4), pancreatic metastases (2.7 vs. 1.4), muscle metastases (5.2 vs. 2.0), and liver metastases (2.8 vs. 0.9), all P<0.001.

CONCLUSIONS: SB scan provides dramatically higher conspicuity of ccRCC metastases as compared with single-bolus portal venous CT.

Group 3 medulloblastoma (G3MB) is a devastating disease of the central nervous system (CNS) that primarily affects infants and children. Chimeric antigen receptor (CAR) T cell therapy holds the promise to improve outcomes for CNS malignancies, but few studies have focused specifically on G3MB. We used publicly available datasets to demonstrate EphA2 and B7-H3 expression in primary G3MB and validated expression in patient-derived cell lines. EphA2-CAR T cells had greater cytolytic activity, persistence, and TH1 cytokine production than B7-H3-CAR T cells in coculture assays with MYC-driven G3MB cell lines in vitro. In vivo, EphA2-CAR T cells demonstrated superior tumor control and improved survival compared to B7-H3-CAR T cells in 2 of 3 orthotopic G3MB models. B7-H3-CAR T cells outperformed EphA2-CAR T cells in one model in which the antigen density of EphA2 was 5-fold lower than for B7-H3. The limited antitumor activity of EphA2-CAR T cells could be overcome with second genetic modifications that increase T cell functionality including deletion of DNMT3A or the expression of a constitutively active IL-18 chimeric cytokine receptor. Thus, our study nominates EphA2-CAR T cells as a promising alternative to B7-H3-CAR T cells, which are actively being explored in clinical studies for medulloblastoma.