カーニー複合

INTRODUCTION: Carney complex (CNC) is a rare autosomal dominant syndrome characterized by multiple endocrine and non-endocrine tumors. In childhood, Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) may occur, while growth hormone (GH) hypersecretion before puberty is exceptionally rare. CASE PRESENTATION: A 5-year-old girl presented with rapid weight gain, facial changes, hypertension, hypokalemic alkalosis, and kidney stones. Biochemical evaluation confirmed ACTH-independent Cushing's syndrome, and abdominal magnetic resonance imaging (MRI) revealed bilateral adrenal nodules consistent with PPNAD. Family history of endocrine tumors and cardiac myxomas suggested CNC, subsequently confirmed by genetic testing showing a mutation of the PRKAR1A gene in both the patient and her father. Bilateral adrenalectomy resolved hypercortisolism. At 8.6 years, the patient showed an accelerated growth velocity (+2.48 SDS) with elevated IGF-1 levels and lack of GH suppression during an oral glucose tolerance testing, despite a normal pituitary MRI. She remained asymptomatic apart from growth acceleration, which was carefully monitored during follow-up. Over 18 months accelerated growth persisted with pubertal progression, but IGF-1 levels eventually normalized and brain MRI remained stable; therefore, treatment for GH excess was deferred. CONCLUSIONS: This case highlights the importance of considering CNC in pediatric ACTH-independent Cushing's syndrome and underlines the role of genetic testing. It also demonstrates that GH hypersecretion may emerge earlier than current screening recommendations, underscoring the need for surveillance starting at the onset of puberty.

Enzyme-induced self-assembling peptides (EISAPs) are a promising class of enzyme-activated anticancer therapeutics, yet their translational screening is limited by the lack of 3D tumor models that effectively capture drug penetration, self-assembly dynamics, and treatment response. To address this need, we developed a pillar-perfusion 3D breast cancer spheroid platform to screen a six-peptide panel-P1 (Fmoc-FF-pTyr), P2 (Fmoc-FF-pThr), P3 (RGD-FF-pTyr), P4 (NBD-FF-pTyr), P5 (Nap-FF-pTyr), and P6 (Nap-FF-pThr)-under static and dynamic flow. Hydrogel optimization identified a 2% gelatin/1% alginate matrix enabling >90% spheroid transfer efficiency and stable non-invasive morphology, while Matrigel-based embedding generated invasive spheroids mimicking metastatic behavior. Across the peptide panel, P1 and P5 produced the strongest cytotoxic effects, with dynamic perfusion further enhancing activity (P1 viability ∼55% at 100 μM). Co-treatment with P1 + 5 μM Doxorubicin resulted in enhanced viability loss and complete inhibition of invasion. Fluorescence imaging of NBD-FF-pTyr confirmed progressive intratumoral penetration and core accumulation over 5 days. RT-qPCR analysis demonstrated peptide- and subtype-specific transcriptional effects, with P1 in MCF-7 spheroids significantly downregulating BCL2, BRCA2, and TP53, while P5 in MDA-MB-231 spheroids produced the strongest repression of survival and DNA-repair pathways. These findings establish a dynamic, high-throughput 3D platform for comparative EISAP screening and demonstrate the therapeutic potential of enzyme-responsive peptides in complex tumor microenvironments.

INTRODUCTION: The immediate postinjury immune response contributes in a complex manner to trauma-induced coagulopathy. The necessary transfusion of blood components can further impact a patient's immune response, creating a poorly understood cycle of transfusion, inflammation, and coagulopathy. The purpose of this study is to define the relationship between large volume transfusion and variations in the immune response following injury. METHODS: Utilizing the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial dataset, the time and volume of transfused blood products were compared to patients' inflammatory cascade for 72 h following injury. In order to model variations in the times and volumes of transfused blood products, time-varying effect modeling was used to assess cytokine response. RESULTS: A total of 522 patients were included in the analysis. A statistically significant correlation in IL 6, IP 10, MIP 1B, and RANTES levels was observed in response to volume and tempo of blood product administration. CONCLUSIONS: Cytokine levels in the acute post-traumatic period are related to blood product transfusion in a time- and volume-dependent manner, specifically showing increases in proinflammatory cytokine and chemokine signaling. An understanding of how blood product administration affects these cytokine signatures can help guide resuscitation practices and represents a potentially novel target for therapeutic intervention.

BACKGROUND: Cardiac myxomas are common benign primary cardiac tumors; hereditary forms are strongly associated with the Carney complex. CASE SUMMARY: A 42-year-old woman with familial Carney complex and a pathogenic PRKAR1A variant developed recurrent cardiac myxomas involving 3 of the 4 chambers. The first presentation featured left atrial and right ventricular myxomas causing cardioembolic cerebellar stroke. A first recurrence in the left atrium caused severe transmitral obstruction and decompensated heart failure. A second recurrence in the right atrium presented as an infected myxoma. A third recurrence arose from the tricuspid annulus 4 months after resection; because further reoperation after 2 prior sternotomies and a right thoracotomy was considered prohibitive, she was listed for transplantation but died suddenly while awaiting transplant. DISCUSSION: This case highlights the aggressive, recurrent, and clinically heterogeneous phenotype and fatal course of Carney complex-associated cardiac myxoma. TAKE-HOME MESSAGE: Early recognition, lifelong surveillance, and timely consideration of advanced strategies are essential in selected patients with recurrent disease.