Hinge Craniotomy for Posterior Cranial Vault Expansion: Using the Keel to the Surgeon's Advantage.

Cranial vault reconstructions are a common craniofacial procedure utilized to treat chronically elevated intracranial pressure and its sequelae for children with craniosynostosis. These surgeries often involve split-thickness autologous grafts to facilitate intracranial volume expansion. The hinge craniotomy was developed by neurosurgeons in the early 2000s as an alternative to the hemicraniectomy to allow for greater space and simplified re-securing of the bone flap. In our report, we introduce a novel application of hinge craniotomy in total cranial vault reconstruction for a pediatric patient with microcephaly secondary to congenital cytomegalovirus infection. We performed bilateral barrel stave cuts to the occipital bone as well as an undercut along the midline keel to form a hinge craniotomy. Complex reconstruction followed to augment intracranial volume and restructure the cranial vault. This technique maximized intracranial volume expansion while minimizing the need for prolonged reconstruction. It also allowed for retained vascularization of the bone flap by maintaining the connection with the intact cranial base and pericranium to further support bony healing. Our study presents a novel utilization of hinge craniotomy, using the occipital keel as a natural hinge, to create ample space during cranial vault reconstruction. This technique offers potential advantages in terms of intracranial volume expansion and bony healing.

Co-culture of vascular endothelial cells enhances corticosterone production in steroid hormone-producing cells generated from adipose-derived mesenchymal stromal cells.

Cell therapy for adrenocortical insufficiency can potentially provide steroid replacement in response to physiological stimuli. Previously, we reported that adipose tissue-derived stromal cells (ADSCs) are transformed into steroid-producing cells by overexpression of nuclear receptor subfamily 5 group A member 1 (NR5A1). The steroidogenic cells are characterized by the production of both adrenal and gonadal steroids. Cytotherapy for adrenocortical insufficiency requires cells with more adrenocortical characteristics. Considering the highly developed vascular network within the adrenal cortex, all adrenocortical cells are adjacent to and interact with vascular endothelial cells (VECs). In this study, NR5A1-induced steroidogenic cells derived from mouse ADSCs (NR5A1-ADSCs) were co-cultured with mouse VECs. Testosterone secretion in NR5A1-ADSCs was not altered; however, corticosterone secretion significantly increased while levels of steroidogenic enzymes significantly increased in the corticosterone synthesis pathway. Co-culture with lymphatic endothelial cells (LECs) or ADSCs, or transwell culture with NR5A1-ADSCs and VECs did not alter corticosterone production. VECs expressed higher levels of collagen and laminin than LECs. Culture in type-IV collagen and laminin-coated dishes increased corticosterone secretion in NR5A1-ADSCs. These results suggest that VECs may characterize ADSC-derived steroidogenic cells into a more corticosterone-producing phenotype, and VECs may be useful for generating adrenal steroidogenic cells from stem cells.

Placement of Endovascular Stent for Reperfusion of Cerebral Infarct After Pediatric Traumatic Internal Carotid Artery Dissection.

Background: Traumatic intracranial ICA dissections are not commonly seen in children. Dissection resulting in perfusion deficit warrants intervention. Here we encountered a patient who experienced traumatic ICA dissection, treated by endovascular stenting. Methods: A 10-year-old female presented with aphasia and right sided weakness following trauma. Imaging showed deficit in the left MCA territory without core. Further imaging showed dissection of the left supraclinoid ICA, confirmed by digital subtraction angiography. Results: A Neuroform Atlas stent was placed without complication. All dysarthria and weakness had resolved on follow-up 5 months post-stenting. Conclusions: Acute stroke symptoms in children can result in lasting deficits if not treated quickly. Medical management is regarded to be first line, depending on presentation. Endovascular stenting may provide a promising means to treat pediatric ICA dissections involving perfusion deficits and mitigate permanent ischemic changes.

Isolation of mucosa-associated microbiota dysbiosis in the ascending colon in hepatitis C virus post-sustained virologic response cirrhotic patients.

Background: Achieving sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) reduces all-cause mortality. However, the mechanisms and risk factors for liver fibrosis and portal hypertension post-SVR remain incompletely understood. In the gut-liver axis, mucosa-associated microbiota (MAM) substantially influence immune and metabolic functions, displaying spatial heterogeneity at the anatomical intestinal site. We analyzed MAM composition and function to isolate the locoregional MAM involved in chronic liver disease progression in HCV post-SVR patients. Methods: We collected MAM samples from three intestinal sites (terminal ileum, ascending colon, and sigmoid colon) via brushing during colonoscopy in 23 HCV post-SVR patients and 25 individuals without liver disease (controls). The 16S rRNA of bacterial DNA in specimens collected with a brush and in feces was sequenced. The molecular expression of intestinal tissues and hepatic tissues were evaluated by quantitative real-time PCR. Results: In the post-SVR group, the microbial ß-diversity of MAM, especially in the ascending colon, differed from the control group and was associated with liver fibrosis progression. In PICRUSt analysis, MAM in the ascending colon in the liver cirrhosis (LC) group showed compromised functions associated with the intestinal barrier and bile acid production, and FGF19 expression was markedly decreased in the terminal ileum biopsy tissue in the LC group. At the genus level, six short-chain fatty acid (SCFA)-producing bacterial genera, Blautia, Alistipes, Roseburia, Agathobaculum, Dorea, and Pseudoflavonifractor were reduced in the ascending colon of post-SVR LC patients. Conclusion: In patients of HCV post-SVR, we identified the association between the degree of liver fibrosis and dysbiosis of mucosa-associated SCFA-producing bacterial genera that may be related to intestinal barrier and bile acid production in the ascending colon.

Rapid multiplex real-time PCR assay using a portable device for the detection of oral pathogens.

Colonization by several oral pathogens and the onset of oral diseases, such as dental caries and periodontal diseases, are closely related. Therefore, the analysis of pathogens in oral specimens would be helpful for the risk assessment of oral diseases. We developed a rapid multiplex real-time polymerase chain reaction (PCR) method using a portable device and newly designed probe/primer sets to detect the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. The theoretical minimum detectable cell numbers of S. mutans, P. gingivalis, T. denticola, and T. forsythia were 1, 1, 4, and 3, respectively. The multiplex real-time PCR system simultaneously detected the colonization of S. mutans and P. gingivalis in human saliva. These results suggest that the multiplex real-time PCR system may be useful for the risk assessment of oral diseases.

Serial Changes of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab.

Immune checkpoint inhibitors have promising outcomes in patients with hepatocellular carcinoma (HCC); however, there is no reliable biomarker for predicting disease progression. Circulating tumor cells (CTCs) derived from peripheral blood have attracted attention in monitoring therapeutic efficacy. In this study, CTCs were serially collected from HCC patients undergoing atezolizumab plus bevacizumab (Atezo+Bev), and changes in molecular expression and CTC numbers were analyzed to identify effective biomarkers. Changes in CTC numbers during Atezo+Bev reflected the tumor volume. Targeted RNA sequencing with next-generation sequencing (NGS) revealed that patients with elevated transforming growth factor (TGF)-ß signaling molecules had a poorer response, whereas those with elevated apoptosis signaling molecules had a favorable response. In addition, compared with changes in CTC counts, changes in TGF-ß signaling molecule expression in CTCs accurately and promptly predicted treatment response. Overall, NGS analysis of CTC-derived RNA showed that changes in TGF-ß signaling molecules predict treatment response earlier than changes in CTC counts. These findings suggest that changes in the expression of TGF-ß molecules in CTCs could serve as novel biomarkers for the early prediction of therapeutic response in patients with unresectable HCC undergoing Atezo+Bev.

Programmed Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor and Monitor of Response to Atezolizumab plus Bevacizumab Treatment in Patients with Hepatocellular Carcinoma.

There remains no reliable biomarker of therapeutic efficacy in hepatocellular carcinoma (HCC) for the PD-L1 inhibitor atezolizumab and bevacizumab (Atezo/Bev). Circulating tumor cells (CTCs) enable the serial collection of living tumor cells. Pre-treatment and serial CTC gene expression changes and tumor histology were evaluated to identify predictors of response to Atezo/Bev. Peripheral blood from 22 patients with HCC treated with Atezo/Bev and 24 patients treated with lenvatinib was serially collected. The RNA expression in CTCs was analyzed using qRT-PCR. Higher PD-L1 expression in pre-treatment CTCs was associated with response and improved prognosis with Atezo/Bev treatment, but not with lenvatinib. There was no correlation between PD-L1 expression in CTCs and that in liver tumor biopsy specimens scored using imaging software. Furthermore, PD-L1 RNA expression in CTCs was dynamically altered by Atezo/Bev, decreasing during effective response and increasing upon progression. CTC-derived RNA collected during Atezo/Bev indicates that patients with higher PD-L1 expression in CTCs at baseline were 3.9 times more responsive to treatment. Therefore, PD-L1 RNA levels in CTCs are an accurate response predictor and may be a monitorable biomarker that changes dynamically to reflect the response during Atezo/Bev treatment.