Inpatient continuous thalamic stereo-electroencephalography stimulation in the evaluation of focal epilepsy: illustrative case.
Hidalgo Monroy Lerma B, Makhoul GS, Reda A, Cavender AC, Doss DJ, Withers CP, Wang K, Johnson GW, Funk C, Crudele AN, Englot DJ.
J Neurosurg Case Lessons. 2026 Apr 6;11(14):CASE25947. doi: 10.3171/CASE25947. Print 2026 Apr 6.
PMID: 41941831 Free PMC article.
Abstract
Background: In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, thalamic neuromodulation targeting structures such as the anterior nucleus of the thalamus (ANT), centromedian nucleus (CM), and pulvinar (PUL) has emerged as a promising therapy. The clinical investigation of these targets’ efficacy and side effect profiles is ongoing, complicating discussions between neurosurgeons, neurologists, and patients. The implementation of single-pulse and continuous stimulation protocols to conduct patient-specific side effect screens and generate prognostic biomarkers could offer guidance for target selection.
Observations: A 32-year-old male with extensive polymicrogyria and DRE underwent stereo-electroencephalography (SEEG) with multisite thalamic sampling to inform neuromodulation target selection. Single-pulse stimulation was conducted to screen for acute sensorimotor effects, followed by continuous (12- to 24-hour) stimulation using clinically relevant parameters. Intolerable paresthesia occurred during CM single-pulse stimulation, leading to its exclusion as a target. Single-pulse and continuous stimulation of the ANT and PUL were well tolerated. PUL stimulation offered superior suppression of epileptiform discharges during sleep.
Lessons: These findings meaningfully informed the selection of the PUL as a neuromodulation target. This case illustrates the safety, feasibility, and utility of patient-specific single-pulse and continuous stimulation assessments during SEEG monitoring to evaluate efficacy and tolerability prior to chronic neuromodulation, particularly for novel thalamic targets. https://thejns.org/doi/10.3171/CASE25947.
Keywords: epilepsy; functional neurosurgery; neuromodulation; stereo-EEG; thalamus.
Identifying and Improving LGBTQ + Health Competencies in First-Year Medical Undergraduate Education via a Targeted, Peer-Led Educational Intervention.
Kittleson AR, Nichols CM, Castleman CH, Wooder ER, Wang G, Liu J, Matthews A, Terndrup CP, Allon S.
J Med Educ Curric Dev. 2026 Apr 7;13:23821205261441402. doi: 10.1177/23821205261441402. eCollection 2026 Jan-Dec.
PMID: 41960181 Free PMC article.
Abstract
Purpose: LGBTQ + individuals experience significant health disparities, driven in part by a lack of provider knowledge, necessitating effective interventions for medical trainees. This study examined the impact of a 1-h educational intervention for first-year medical students on 6 self-reported competency domains in LGBTQ + health and compared the magnitude of score changes for competencies specifically targeted by the lecture to those that were not.
Methods: This was a quasi-experimental study. Surveys were distributed before and after a 1-h lecture delivered by an LGBTQ+-identifying senior medical student. Respondents reported data on LGBTQ + identification and prior experience with LGBTQ + health-related topics, and they rated their ability to perform each of 6 LGBTQ + health competencies. Two faculty members with LGBTQ + health expertise blindly reviewed the material and identified which competencies were addressed.
Results: Our sample consisted of 38 matched survey response pairs. Students reported significant increases across all 6 competencies, with no significant difference in score changes between competencies that were targeted by the lecture and those that were not. Prior training in LGBTQ + health-related topics did not significantly affect competency scores. LGBTQ + identity was associated with greater score increases for targeted, but not non-targeted, competencies.
Conclusion: This study demonstrates that a 1-h, LGBTQ+-identifying student-delivered lecture can significantly increase students’ self-reported comfort with LGBTQ + patient care, regardless of LGBTQ + status or prior training. Scores improved for all competencies, regardless of whether they were targeted by the lecture. Further study is indicated to measure whether increases in competency scores are maintained throughout medical training.
Keywords: LGBTQ + health; competency-based evaluation; health competency; sexual/gender minority; undergraduate medical education.
Elevated oxygen extraction during heart transplantation is associated with increased morbidity and mortality: Implications for goal-directed perfusion.
Petrovic M, Ahmad A, Wang CC, Williams AM, Trahanas J, Bommareddi S, Absi T, Quintana E, McGann K, DeVries S, Lowman J, Rali AS, Siddiqi H, Amancherla K, Tsai S, Brinkley M, Menachem JN, Pedrotty D, Punnoose L, Lindenfeld J, Sacks S, Zalawadiya S, Lepore A, Warhoover M, Bacchetta M, Schlendorf K, Shah AS, Lima B.
JTCVS Open. 2025 Dec 8;29:101554. doi: 10.1016/j.xjon.2025.101554. eCollection 2026 Feb.
PMID: 41960089 Free PMC article.
Abstract
Background: Goal-directed perfusion (GDP) during cardiopulmonary bypass (CPB) commonly targets indexed oxygen delivery (DO2i), yet fixed delivery thresholds may ignore patient-specific metabolic demand. The oxygen extraction ratio (O2ER) integrates delivery and consumption and may better reflect supply-demand balance during heart transplantation. We evaluated whether intra-CPB O2ER burden is associated with adverse outcomes after adult heart transplantation and whether O2ER provides incremental prognostic value beyond DO2i.
Methods: We retrospectively analyzed adult heart transplantations performed at a single center between November 2021 and June 2025. Minute-level CPB data were extracted. O2ER was the primary exposure, and the primary outcome was a composite morbidity-mortality (M-M) endpoint (severe primary graft dysfunction [PGD], ventilation for >72 hours, intensive care unit length of stay >15 days, renal replacement therapy, or 90-day mortality). Generalized propensity score-weighted logistic regression modeled associations adjusting for prespecified donor/recipient/procedural covariates. Comparative models assessed O2ER versus DO2i. A post hoc analysis quantified pre- and post-reperfusion O2ER area under the receiver operating characteristic curve (AUC) to localize phase-specific risk.
Results: Among 381 heart transplant recipients, 40 (10.5%) experienced M-M. O2ER trajectories separated between the M-M and non-M-M groups during the mid-procedure window (∼35-100 minutes). Each additional 10 minutes at O2ER > 0.20 was associated with higher odds of M-M (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.00-1.15; P = .043) and 90-day mortality (OR, 1.13; 95% CI, 1.02-1.26; adjusted P = .02). Adding time at O2ER > 0.20 improved a DO2i < 280-only model (P = .04), whereas adding DO2i below-time to an O2ER-only model did not (P = .30). Phase-specific analysis showed that post-reperfusion O2ER AUC was independently associated with M-M (OR, 1.23; 95% CI, 1.08-1.40; P = .002) and severe PGD (OR, 1.22; 95% CI, 1.04-1.43; P = .01), while pre-reperfusion O2ER AUC was related to 90-day mortality (OR, 1.05; 95% CI, 1.004-1.10; P = .03).
Conclusions: During heart transplantation, a higher O2ER burden on CPB is linearly associated with increased post-transplant morbidity and early mortality and contributes prognostic information beyond DO2i. These data support an O2ER-guided GDP strategy that minimizes time (or AUC) above O2ER thresholds, with heightened vigilance regarding reperfusion. Prospective validation is warranted.
Keywords: cardiopulmonary bypass; goal directed perfusion; heart transplantation; oxygen delivery; oxygen extraction ratio.
Prolonged Wnt3a exposure tolerizes macrophages to inflammatory stimuli.
Tigue ML, Jagarlamudi R, Chi C, Diaz D, Chen HC, Sheng Q, Chen SC, Schwarzkopf A, Goettel JA, Pua HH, Lee E, Weiss VL.
Front Immunol. 2026 Mar 12;17:1752131. doi: 10.3389/fimmu.2026.1752131. eCollection 2026.
PMID: 41909666 Free PMC article.
Abstract
Introduction: Macrophages are highly plastic innate immune cells that have a broad range of phenotypic and functional roles in the body. The Wnt/β-catenin signaling pathway is known to play important roles in regulating the immune system, but the literature contains contradictory evidence for how Wnt impacts macrophages. Given the plasticity of macrophages, as well as the growing interest in utilizing Wnt inhibitors therapeutically, there is a need to better understand how Wnt signaling affects macrophage phenotype and function.
Methods: We treated murine bone marrow derived macrophages with Wnt3a, LPS/IFN-γ, or IL-4 and measured gene/protein expression with bulk RNA sequencing, RT-qPCR, flow cytometry, and immunofluorescence to assess macrophage phenotype.
Results: RNA sequencing of macrophages treated continually for 5 days with Wnt3a demonstrated upregulation in genes associated with chemotaxis, cytokine activity, and both pro- and anti-inflammatory phenotypes. A time-course of Wnt3a treatment revealed acute upregulation of the inflammatory cytokines Il6, Tnf, and Il12b. Later timepoints showed upregulation of regulatory markers, such as Il10. Finally, re-treating with classic inflammatory cytokines revealed a Wnt-induced tolerant phenotype.
Discussion: In this study, we expanded upon past work to show that acute stimulation by Wnt3a induces inflammatory activation of macrophages in a time-dependent manner. Chronic stimulation with Wnt3a, as may be expected in a Wnt-ligand rich tissue microenvironment, caused macrophages to become tolerant to additional inflammatory stimuli and to upregulate markers of an anti-inflammatory phenotype. This study highlights the importance of considering time-dependent plasticity and regulatory feedback mechanisms in understanding macrophage phenotypes.
Keywords: Wnt signaling; Wnt3a; macrophages; plasticity; regulation; tolerance.
Divergent Mechanisms of Cranial Suture Ossification in Normal Development and Pathologic Fusion.
Reddy A, Qaddo S, Li P, Gautama B, Abbott E, Dean Y, Means A, Golinko M, Bonfield C, Thayer W, Perdikis G, Pontell M.
J Cell Mol Med. 2026 Apr;30(7):e71125. doi: 10.1111/jcmm.71125.
PMID: 41945928 Free PMC article. Review.
Abstract
Cranial sutures are dynamic growth sites that balance bone growth with mesenchymal patency to accommodate cranial expansion during development. While intramembranous ossification has traditionally been considered the default mechanism of suture fusion, accumulating evidence demonstrates that endochondral pathways might also play a significant role under both physiological and pathological conditions. In this review, we contrast normal developmental ossification processes with premature fusion in craniosynostosis, integrating histological, molecular, and imaging data. We highlight the context-dependent nature of cranial suture biology, influenced by embryonic origin, local signalling gradients, and genetic perturbations. Recognizing divergent ossification mechanisms reframes our understanding of both normal and premature suture fusion and has clinical implications for mechanism-specific therapeutic strategies. Finally, we outline areas for future investigation, including high-resolution profiling of human sutures across developmental stages, to establish a normative framework for cranial suture biology and inform mechanism-driven regenerative approaches.
Keywords: bone formation; cranial development; cranial suture biology; craniosynostosis; ossification mechanisms; skull growth; stem and progenitor cells.
Topoisomerase I inhibitor antibody-drug conjugates in breast cancer: the relevance of the DNA damage response to resistance, response, and combination treatment strategies.
Wang DK, Steele JA, Opalenik SR, Balko JM.
Breast Cancer Res Treat. 2026 Apr 17;217(2):17. doi: 10.1007/s10549-026-07964-y.
PMID: 41991718 Review.
Abstract
Introduction: Antibody drug conjugates (ADCs) have revolutionized cancer treatment. ADCs that contain topoisomerase I inhibitors have been especially important in breast cancer treatment. Despite the substantial progress brought about by these ADCs, there remains a critical need to explore combination treatment strategies to overcome resistance and enhance the efficacy of these agents. Topoisomerase I inhibitors induce DNA damage and thus activate the DNA damage response (DDR). DDR elements have been examined in terms of their role in resistance and response to topoisomerase I inhibitors, and DDR inhibitors may be especially powerful when combined with topoisomerase I inhibitors.
Methods: This review will discuss the topoisomerase I inhibitor ADCs approved for breast cancer treatment, the relevance of select components of the DNA damage response to topoisomerase I inhibitor-containing therapies, and combination strategies with inhibitors of DNA damage response, specifically focusing on inhibitors of poly (ADP-ribose) polymerase (PARP) and the ataxia-telangiectasia mutated and Rad3-related (ATR) inhibitor. CONCLUSIONS: The introduction of topoisomerase inhibitors as an ADC payload into breast cancer care has redefined a need to better understand the intricacies of their mechanism of action and tumor methods of escape and resistance, hopefully leading to novel synergistic therapeutic strategies.
Keywords: ATR inhibition; Antibody–drug conjugates (ADCs); Breast cancer; DNA damage response inhibitors; Topoisomerase I inhibition.
Tissue and CD4 T cell subset dependence on the amino acid transporter SLC38A1.
Sugiura A, Beier KL, Chi C, Heintzman DR, Ye X, Wolf MM, Patterson AR, Cephus JY, Hong HS, Perera JM, Lyssiotis CA, Newcomb DC, Rathmell JC.
Cell Metab. 2026 Apr 7;38(4):712-728.e6. doi: 10.1016/j.cmet.2026.02.016. Epub 2026 Mar 23.
PMID: 41875885 Free PMC article.
Genetically-predicted placental gene expression links to uterine fibroids and endometriosis.
Akerele AT, Hampton G, Kim J, Jaworski J, Lewis TJ, Khan A, Rasmussen-Torvik LJ, Luo Y, Jasper EA, Hellwege JN, Edwards TL, Velez Edwards DR.
Placenta. 2026 Apr 1;179:14-22. doi: 10.1016/j.placenta.2026.03.023. Online ahead of print.
PMID: 41936293 Free article.
Early Cochlear Implant Outcomes Predict Long-Term Speech Recognition.
Chau IJ, Kunnath AJ, Gothard A, Dixon PR, Gifford RH, Harvey EA, Haynes DS, Holder JT, Patro A, Perkins EL, Tamati TN, Hand BN, McRackan TR, Moberly AC.
Ear Hear. 2026 May-Jun 01;47(3):790-797. doi: 10.1097/AUD.0000000000001774. Epub 2025 Dec 17.
PMID: 41403015 Free PMC article.
Pathobiont-triggered induction of goblet cell response drives regional susceptibility to inflammatory bowel disease.
Spencer PN, Brown ME, Smith EP, Wang J, Kim W, Spiga L, Tasneem N, Simmons AJ, Kim T, Yang Y, Xu Y, Zheng L, Ro J, Kaur H, Kang SW, Helou MD, Lee MA, Arceneaux D, Mueller KD, Kuddar OS, Harned MH, Li J, Banerjee A, Markham NO, Wilson KT, Coburn LA, Goettel JA, Liu Q, Washington MK, Valdivia RH, Zhu W, Lau KS.
J Clin Invest. 2026 Feb 17;136(7):e201729. doi: 10.1172/JCI201729. eCollection 2026 Apr 1.
PMID: 41701533 Free PMC article.
Overnutrition in mice impairs thyroid hormone biosynthesis and utilization, causing hypothyroidism, despite remarkable thyroidal adaptations.
Rampy J, Torres-Manzo AP, Hoffsmith K, Loberg MA, Sheng Q, Salas-Lucia F, Bianco AC, Arrojo E Drigo R, Wang H, Weiss VL, Carrasco N.
J Clin Invest. 2026 Apr 15;136(8):e194207. doi: 10.1172/JCI194207. eCollection 2026 Apr 15.
PMID: 41983397 Free PMC article.
Cohort-Aware Agents for Individualized Lung Cancer Risk Prediction Using a Retrieval-Augmented Model Selection Framework.
Qu C, Luna AJ, Li TZ, Zhu J, Guo J, Xiong J, Sandler KL, Landman BA, Huo Y.
Proc SPIE Int Soc Opt Eng. 2026 Feb;13926:139262M. doi: 10.1117/12.3087567. Epub 2026 Apr 2.
PMID: 41987941 Free PMC article.
Determining an optimal central cannulation strategy for ambulatory veno-venous extracorporeal life support.
Kumpfbeck AR, Woo Y, Petrovic M, Simon V, Cortelli M, Adjei E, Petree B, Simonds E, Adesanya T, Cagnolatti C, Shishido Y, Bapatla S, Stokes JW, Trachtman E, Skoog DJ, Cook KE, Demarest CT, Bacchetta M, Ukita R.
J Heart Lung Transplant. 2026 Mar 30:S1053-2498(26)01760-2. doi: 10.1016/j.healun.2026.02.1682. Online ahead of print.
PMID: 41949527 Free article.
Donor Heart Undersizing Impacts Early Hemodynamics But Not 1-Year Survival in Adult Heart Transplantation-A High-Volume Single Center 5-Year Experience.
Williams AM, Wang CC, Trahanas J, Lima B, Ahmad A, McGann KC, Petrovic M, Devries S, Lowman J, Absi T, Quintana E, Schlendorf K, Bacchetta M, Shah AS, Bommareddi S.
J Thorac Cardiovasc Surg. 2026 Apr 3:S0022-5223(26)00846-9. doi: 10.1016/j.jtcvs.2026.03.606. Online ahead of print.
PMID: 41936999
Unadjusted Confounding in the Association Between Clonal Hematopoiesis and Heart Failure After Cancer Therapy-Reply.
Shyr D, Pershad Y, Bick AG.
JAMA Oncol. 2026 Apr 16. doi: 10.1001/jamaoncol.2026.0779. Online ahead of print.
PMID: 41989772 No abstract available.
Clonal Hematopoiesis and Risk of Stroke: Evidence From Over 800 000 Individuals Across 3 Cohorts.
Zhao K, Pershad Y, Xue L, Vlasschaert C, Corty RW, Heimlich JB, Kooperberg C, Reiner AP, Bick AG.
Stroke. 2026 Apr 8. doi: 10.1161/STROKEAHA.125.054128. Online ahead of print.
PMID: 41948817
Adipose-Derived Stem Cell-Enhanced versus Conventional Fat Grafting for Breast Reconstruction: A Systematic Review and Meta-Analysis.
Lee E, Reddy A, Gutama B, Karamitros G, Abbas H, Zhang F, Lineaweaver W.
Plast Reconstr Surg. 2026 Mar 30. doi: 10.1097/PRS.0000000000013089. Online ahead of print.
PMID: 41910338 No abstract available.
Macrodystrophia Lipomatosis Macrodactyly.
Rashidi A, Witt A, Arunachalam VS, Lam PL, Gulati V.
Radiographics. 2026 May;46(5):e250248. doi: 10.1148/rg.250248.
PMID: 41989926 No abstract available.