Adipose-derived exosomes as a preventative strategy against complications in hyaluronic acid filler applications: A comprehensive in vivo analysis.

BACKGROUND: The aim of this study was to investigate the impact of exosomes derived from adipose-derived stem cells (ASCs) on complications arising from hyaluronic acid (HA) filler injections. METHODS: An HA hydrogel blended with adipose stem cell-derived exosomes was prepared and administered to the inguinal fat pads of 16 C57BL/6J mice. The control group received only HA filler (HA group), and the study group was treated with a combination of HA filler and exosomes (exoHA group). Biopsy was performed 1 week and 1, 2, 3, and 6 months after the injections. The effects were assessed using hematoxylin and eosin and Masson's trichrome staining for histological examination, immunohistochemistry for collagen type I and Vascular Endothelial Growth Factor (VEGF), RNA sequencing, and quantitative real-time polymerase chain reaction (PCR) (Il6, Ifng, Hif1a, Acta2, Col1a1). RESULTS: RNA sequencing revealed significant downregulation of the hypoxia (false discovery rate [FDR] q = 0.007), inflammatory response (FDR q = 0.009), TNFα signaling via NFκB (FDR q = 0.007), and IL6 JAK-STAT signaling (FDR q = 0.009) gene sets in the exoHA group. Quantitative PCR demonstrated a decrease in expression of proinflammatory cytokines (Il6, P < 0.05; Hif1a, P < 0.05) and fibrosis markers (Acta2, P < 0.05; Col1a1, P < 0.05) within the exoHA group, indicating reduced inflammation and fibrosis. Compared to the exoHA group, the HA group exhibited a thicker and more irregular capsules surrounding the HA filler after 6 months. CONCLUSION: The addition of ASC-derived exosomes to HA fillers significantly reduces inflammation and accelerates collagen capsule maturation, indicating a promising strategy to mitigate the formation of HA filler-related nodules.

Clinical Applicability and Safety of Conventional Frame-Based Stereotactic Techniques for Stereoelectroencephalography.

Objective: Stereoelectroencephalography (SEEG) is increasingly being recognized as an important invasive modality for presurgical evaluation of epilepsy. This study focuses on the clinical and technical considerations of SEEG investigations when using conventional frame-based stereotaxy, drawing on institutional experience and a comprehensive review of relevant literature. Methods: This retrospective observational study encompassed the surgical implantation of 201 SEEG electrodes in 16 epilepsy patients using a frame-based stereotactic instrument at a single tertiary-level center. We provide detailed descriptions of the operative procedures and technical nuances for bilateral and multiple SEEG insertions, along with several illustrative cases. Additionally, we present a literature review on the technical aspects of the SEEG procedure, discussing its clinical implications and potential risks. Results: Frame-based SEEG electrode placements were successfully performed through sagittal arc application, with the majority (81.2%) of cases being bilateral and involving up to 18 electrodes in a single operation. The median skin-to-skin operation time was 162 minutes (interquartile range [IQR], 145-200), with a median of 13 minutes (IQR, 12-15) per electrode placement for time efficiency. There were two occurrences (1.0%) of electrode misplacement and one instance (0.5%) of a postoperative complication, which manifested as a delayed intraparenchymal hemorrhage. Following SEEG investigation, 11 patients proceeded with surgical intervention, resulting in favorable seizure outcomes for nine (81.8%) and complete remission for eight cases (72.7%). Conclusion: Conventional frame-based stereotactic techniques remain a reliable and effective option for bilateral and multiple SEEG electrode placements. While SEEG is a suitable approach for selected patients who are strong candidates for epilepsy surgery, it is important to remain vigilant concerning the potential risks of electrode misplacement and hemorrhagic complications.

Unbiased transcriptome analysis of human cleft palate reveals evolutionally conserved molecular signatures of development: experimental study.

BACKGROUND: The development of the secondary palate, an essential process for hard palate formation, involves intricate cellular processes. Here, we examined the expression patterns of palatal fusion-associated genes in postdevelopmental human palatal tissues. METHODS: Mucosal samples collected from the anterior fused (control; n=5) and posterior unfused regions (study; n=5) of cleft palate patients were subjected to RNA sequencing. Gene Set Enrichment Analysis (GSEA) was conducted to identify consistent changes in molecular signaling pathways using hallmark (h) gene set collections from the Molecular Signature Database v7.4. The results of RNA sequencing were validated by epithelial-mesenchymal transition (EMT) assays with suppression of target genes, including lrp6, shh, Tgfß-3 (Bioneer, Daejeon, Korea), and negative control siRNA in a human fibroblast cell line (hs68). RESULTS: Transcriptome profiling of the cleft mucosa demonstrated that the fully fused anterior mucosa exhibited globally upregulated EMT, Wnt ß-catenin, Hedgehog, and TGF-ß signaling pathways in gene set enrichment. This strongly indicates the evolutionary conserved similarities in pathways implicated in palatogenesis, as previously shown in murine models. In EMT assays with suppression of Lrp6, Shh, and TGF-ß3 in human fibroblast cell lines, suppression of Lrp6 exhibited consistent suppression effects on EMT markers. This indicates a closer association with EMT compared to the other two signals. CONCLUSION: Our study highlights evolutionarily conserved molecular signatures and provides insights into the importance of the EMT pathway in palatal fusion in humans. Furthermore, intraindividual comparative analysis showed the spatial regulation of gene expression within the same organism. Further research and animal models are needed to explore the complexities of EMT-related palatal fusion.

Long-Term Comparison of Esthetic Outcomes Between Hatchet and Transposition Flaps in Facial-Defect Reconstruction.

BACKGROUND: Transposition flaps are commonly used for facial-defect repair after wide excision of skin cancers. However, such repair often causes excessive tension at the donor site that can result in distortion of the adjacent area. The hatchet flap, a rotation-advancement flap, can prevent distortion by redistributing the donor site tension evenly to the recipient site. This study aims to compare the esthetic outcomes of the hatchet flap and transposition flap in facial-defect reconstruction. METHODS: We retrospectively included 50 patients who underwent facial reconstruction with the hatchet flap or transposition flap after excision of skin cancer. They were followed up for more than 6 months. At the last follow-up visit, the esthetic outcome was evaluated by subjective and objective assessments using the patients and observer scar assessment scale and Manchester scar scale. RESULTS: Thirty patients and 20 patients underwent reconstruction using the hatchet flap and the transposition flap, respectively. The total score from the patient and observer scar assessment scale was significantly lower in the hatchet flap group compared with the transposition flap group (p = 0.009). The Manchester scar scale showed a total score of 7.67 ± 2.2 for the hatchet flap and 9.95 ± 1.99 for the transposition flap: in the color (p < 0.001), distortion (p < 0.001), and texture (p < 0.02) categories, the hatchet flap yielded significantly better outcomes than the transposition flap. CONCLUSIONS: The hatchet flap had good esthetic outcome for facial reconstruction and could be a valuable option for reconstructing facial defects. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from the Korean Heart Rhythm Society Cryoablation registry.

AIMS: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS AND RESULTS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicentre registry of 12 tertiary hospitals, we analysed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI < 18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). A total of 2648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups: 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. Underweight patients were the oldest and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-years). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared with NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, P = 0.02). Procedure-related complications occurred in 123 (4.7%) patients, and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, P = 0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: Underweight patients showed a higher risk of AF recurrence after cryoablation compared with NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Histone Lysine Demethylase KDM5 Inhibitor CPI-455 Induces Astrocytogenesis in Neural Stem Cells.

Lysine-specific histone demethylase 5A (KDM5A) is known to facilitate proliferation in cancer cells and maintain stemness to repress the astrocytic differentiation of neural stem cells (NSCs). In the study presented here, we investigated the effect of a KDM5 inhibitor, CPI-455, on NSC fate control. CPI-455 induced astrocytogenesis in NSCs during differentiation. Kdm5a, but not Kdm5c, knockdown induced glial fibrillary acidic protein (Gfap) transcription. CPI-455 induced signal transducer and activator of transcription 3, increased bone morphogenetic protein 2 expression, and enhanced mothers against decapentaplegic homolog 1/5/9 phosphorylation. The treatment of CPI-455 enhanced the methylation of histone H3 lysine 4 in the Gfap promoter when compared to that of the dimethyl sulfoxide control. In addition, CPI-455 treatment significantly reduced the recruitment of KDM5A to the Gfap promoter. Our data suggest that the KDM5 inhibitor CPI-455 effectively controls NSC cell fate via KDM5A inhibition and induces astrocytogenesis.

Complete Preservation of Orbital Fat by Restoration of Attenuated Orbital Septa Using an Acellular Dermal Matrix in Lower Blepharoplasty.

BACKGROUND: We hypothesized that application of acellular dermal matrix (ADM) over the orbital septum overlying the herniated orbital fat to tighten and strengthen the attenuated orbital septum in lower blepharoplasty would allow successful repositioning of the herniated orbital fat within the bony orbit. METHODS: The author prospectively compared the cosmetic outcomes of lower blepharoplasty using ADM with standard blepharoplasty. We evaluated recurrence of eyelid bulging and tear trough deformity, volume of the lower periorbital region, and enophthalmos and eyelid droop 1 year after surgery. RESULTS: Twenty-two of the 24 enrolled patients completed the study. There was no significant difference in recurrence of eyelid bulging and tear trough deformity between standard blepharoplasty and blepharoplasty with ADM graft groups. In the standard blepharoplasty group, the volume of the lower periorbital region decreased significantly after surgery. In the blepharoplasty with ADM graft group, there was no significant change in the volume of the lower periorbital region after surgery. In the standard blepharoplasty group, there was no significant change in eyelid droop on either side after surgery. In the blepharoplasty with ADM graft group, the eyelid droop decreased significantly after surgery on the right side but showed no significant change on the left side. There was no significant change in enophthalmos after surgery for either group. CONCLUSIONS: This study demonstrated that ADM graft provided effective support for maintaining the replaced orbital fat in lower blepharoplasty. In the long-term, blepharoplasty with ADM graft might be effective in slowing development of age-related enophthalmos. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Successful surgical attenuation of portosystemic shunt in a dog with imaging-diagnosed portal vein aplasia.

An 8-month-old female Maltese dog was referred for examination with a history of circling, dullness, and drooling. Serum biochemical analysis revealed hyperammonemia, with microhepatica observed on radiography. Computed tomography angiography revealed a portosystemic shunt originating from the right gastric vein and inserting into the prehepatic caudal vena cava. Portal blood flow to the liver was not observed. Based on computed tomography angiography, the dog was tentatively diagnosed with portosystemic shunt with portal vein aplasia. An exploratory laparotomy was done to obtain a definitive diagnosis. The dog had no subjective clinical signs of portal hypertension during a temporary occlusion test of the portosystemic shunt. A thin-film band was placed around the portosystemic shunt to achieve partial attenuation. There was no evidence of hepatic encephalopathy in the long term after surgery, and the dog's liver volume increased over time. Computed tomography angiography at 6 mo after surgery identified well-visualized intrahepatic portal branches. Key clinical message: We inferred that a direct occlusion test is a reliable diagnostic technique that overcomes the limitations of diagnostic imaging methods, including computed tomography angiography, and is a good technique for determining whether surgical attenuation is possible in dogs with suspected portal vein aplasia.

Atténuation chirurgicale réussie d'un shunt porto-systémique chez un chien avec une aplasie de la veine porte diagnostiquée par imagerie. Une femelle bichon maltais âgée de 8 mois a été référée pour examen avec une histoire de tournis, apathie et salivation excessive. L'analyse biochimique du sérum a révélé une hyperammionémie, avec un petit foie observé lors des radiographies. Une angiographie par tomodensitométrie a révélé un shunt porto-systémique prenant son origine de la veine gastrique droite et s'insérant dans la veine cave caudale pré-hépatique. Le flot sanguin porte au foie n'était pas observé. Sur la base de l'angiographie par tomodensitométrie, un diagnostic présumé de shunt porto-systémique avec aplasie de la veine porte a été émis. Une laparotomie exploratoire a été effectuée afin d'obtenir un diagnostic définitif. Le chien ne présentait pas de signe clinique subjectif d'hypertension portale durant un test d'occlusion temporaire du shunt porto-systémique. Une bande de film mince a été placée autour du shunt porto-systémique pour causer une réduction partielle. Il n'y avait aucune évidence d'encéphalopathie hépatique à long terme après la chirurgie, et le volume du foie du chien a augmenté dans le temps. Une angiographie par tomodensitométrie effectuée 6 mo après la chirurgie a permis de bien visualiser des branches portes intra-hépatiques.Message clinique clé :Nous avons déduit qu'un test d'occlusion est une technique diagnostique fiable qui surpasse les limites des méthodes d'imagerie diagnostique, incluant l'angiographie par tomodensitométrie, et est une bonne technique pour déterminer si une réduction chirurgicale est possible chez des chiens chez qui on soupçonne une aplasie de la veine porte.(Traduit par Dr Serge Messier).

The impact of early cryoballoon ablation on clinical outcome in patients with atrial fibrillation: From the Korean cryoballoon ablation registry.

INTRODUCTION: Influence of early atrial fibrillation (AF) ablation, particularly cryoballoon ablation (CBA), on clinical outcome during long-term follow-up has not been clarified. The objective was to determine whether an early CBA (diagnosis-to-ablation of ≤6 months) strategy could affect freedom from AF recurrence after index CBA. METHODS: The study included 2605 patients from Korean CBA registry data with follow-up >12 months after de novo CBA. The primary outcome was recurrence of atrial tachyarrhythmias (ATs) of ≥30-s after a 3-month blanking period. RESULTS: Compared to patients in early CBA group, patients in late CBA group had higher prevalence of diabetes, congestive heart failure, and chronic kidney disease, and higher mean CHA2 DS2 -VAS score. During mean follow-up of >21 months, ATs recurrence was detected in 839 (32.2%) patients. The early CBA group showed a significantly lower 2-year recurrence rate of ATs than the late CBA group (26.1% vs. 31.7%, p = 0.043). In subgroup analysis, the early CBA group showed significantly higher 1-year and 2-year freedom from ATs recurrence than the late CBA group only in paroxysmal atrial fibrillation (PAF) patients in overall and propensity score matched cohorts. Multivariate analysis showed that early CBA was an independent factor for preventing ATs recurrence in PAF (hazard ratio: 0.637; 95% confidence intervals: 0.412-0.984). CONCLUSION: Early CBA strategy, resulting in significantly lower ATs recurrence during 2-year follow-up after index CBA, might be considered as an initial rhythm control therapy in patients with paroxysmal AF.

Perioperative Low-Dose Aspirin Management for Planned Clipping Surgery: When, How Long, and With What Precautions?

BACKGROUND AND OBJECTIVE: Perioperative low-dose aspirin (ASA) management for open craniotomy surgery lacked information. We analyze to establish the perioperative ASA strategy to minimize both hemorrhagic and thromboembolic complications. METHODS: The investigators designed a multicenter retrospective study, which included patients scheduled to have clipping surgery for unruptured intracranial aneurysm. The incidence and risk factors were analyzed for postoperative hemorrhagic complications and major cardio- and cerebrovascular events (MACCEs) within 1 month postoperation. RESULTS: This study included 503 long-term ASA users of 3654 patients at three tertiary centers. The incidence of hemorrhagic complications and MACCEs was 7.4% (37/503) and 8.8% (44/503), respectively. Older age (>70 years, odds ratio [OR]: 2.928, 95% CI [1.337-6.416]), multiple aneurysms operation (OR: 2.201, 95% CI [1.017-4.765]), large aneurysm (>10 mm, OR: 4.483, 95% CI [1.485-13.533]), and ASA continuation (OR: 2.604, 95% CI [1.222-5.545]) were independent risk factors for postoperative hemorrhagic complications. Intracranial hemorrhage was the only type of hemorrhagic complication that increased in the ASA continuation group (10.6% vs 2.9%, P = .001). Between the ASA continuation and discontinuation groups, the overall incidence of MACCEs was not significantly different (log-rank P = .8). In the subgroup analysis, ASA discontinuation significantly increased the risk of MACCEs in the secondary prevention group (adjusted hazard ratio: 2.580, 95% CI [1.015-6.580]). CONCLUSION: ASA continuation increased the risk of postoperative intracranial hemorrhage. Simultaneously, ASA discontinuation was the major risk factor for postoperative MACCEs in the high-risk group. Without evidence of intracranial hemorrhage, early ASA resumption was indicated (a total cessation duration <7-10 days) in the secondary prevention group.

Compromised Accuracy of Stereotactic Target Delineation Associated with Computed Tomography-Based Frame Registration: A Comparative Analysis of Magnetic Resonance Imaging-Computed Tomography Fusion.

INTRODUCTION: Recent advancements in stereotactic neurosurgical techniques have become increasingly reliant on image-based target planning. We devised a case-phantom comparative analysis to evaluate the target registration errors arising during the magnetic resonance imaging (MRI)-computed tomography (CT) image fusion process. METHODS: For subjects whose preoperative MRI and CT images both contained fiducial frame localizers, we investigated discrepancies in target coordinates derived from frame registration based on either MRI or CT. We generated a phantom target through an image fusion process, merging the framed CT images with their corresponding reference MRIs after masking their fiducial indicators. This phantom target was then compared with the original during each instance of target planning. RESULTS: In our investigative study with 26 frame registrations, a systematic error in the y-axis was observed as -0.89 ± 0.42 mm across cases using either conventional CT and/or cone-beam CT (O-arm). For the z-axis, errors varied on a case-by-case basis, recording at +0.64 ± 1.09 mm with a predominant occurrence in those merged with cone-beam CT. Collectively, these errors resulted in an average Euclidean error of 1.33 ± 0.93 mm. CONCLUSION: Our findings suggest that the accuracy of frame-based stereotactic planning is potentially compromised during MRI-CT fusion process. Practitioners should recognize this issue, underscoring a pressing need for strategies and advancements to optimize the process.

Bortezomib Is Toxic but Induces Neurogenesis and Inhibits TUBB3 Degradation in Rat Neural Stem Cells.

Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of ßIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.

Improving Facial Fat Graft Survival Using Stromal Vascular Fraction-Enriched Lipotransfer: A Multicenter Randomized Controlled Study.

BACKGROUND: Although previous clinical studies have reported that cell-assisted lipotransfer increases the fat survival rate in facial fat transplants, most were case studies without quantitative evaluation. A multicenter randomized controlled study was performed to evaluate the safety and efficacy of the stromal vascular fraction (SVF) in facial fat grafts. METHODS: Twenty-three participants were enrolled for autologous fat transfer in the face, and assigned randomly to the experimental ( n = 11) or control ( n = 12) group. Fat survival was assessed using magnetic resonance imaging at 6 and 24 weeks postoperatively. Subjective evaluations were performed by the patients and surgeons. To address safety concerns, results of an SVF culture and the postoperative complications were recorded. RESULTS: The overall fat survival rate was significantly higher in the experimental group than in the control group (6 weeks, 74.5% ± 9.99% versus 66.55% ± 13.77%, P < 0.025; 24 weeks, 71.27% ± 10.43% versus 61.98% ± 13.46%, P < 0.012). Specifically, graft survival in the forehead was 12.82% higher in the experimental group when compared with that in the control group at 6 weeks ( P < 0.023). Furthermore, graft survival in the forehead ( P < 0.021) and cheeks ( P < 0.035) was superior in the experimental group at 24 weeks. At 24 weeks, the aesthetic scores given by the surgeons were higher in the experimental group than in the control group ( P < 0.03); however, no significant intergroup differences were noted in the patient-evaluated scores. Neither bacterial growth from SVF cultures nor postoperative complications were noted. CONCLUSION: SVF enrichment for autologous fat grafting can be a safe and effective technique for increasing the fat retention rate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Ultrasonographic identification of lateral femoral cutaneous nerve anatomical variation in persistent meralgia paresthetica: A case report.

BACKGROUND: Meralgia paresthetica (MP) is an entrapment mononeuropathy of the lateral femoral cutaneous nerve (LFCN). Although structural abnormalities in nerve tissues can be confirmed using ultrasonography, this is not routinely performed. CASE SUMMARY: Herein, we present the case of a 52-year-old woman who developed MP after laparoscopic gynecological surgery. The patient was referred to our clinic from an obstetrics and gynecology clinic with symptoms of numbness and a tingling sensation in the left anterolateral thigh, which developed after surgery performed 5 mo earlier. Tests were performed to assess the disease status and determine the underlying causes. Ultrasonographic examination revealed an anatomical variation, where the left LFCN was entrapped within the inguinal ligament. This case suggests that performing ultrasonographic examination before and after surgery in the lithotomy position could help prevent MP. CONCLUSION: This case demonstrates the value of ultrasonography in detecting anatomical variation and diagnosing persistent MP. Ultrasonography should be considered an adjunct to electromyography for optimal MP management. Further, this case would help other clinicians determine patient prognosis and decide on targeted treatment strategies.

A Potential Risk of Radiation-Induced Cavernous Malformations Following Adjuvant Gamma Knife Radiosurgery for Mesial Temporal Lobe Epilepsy.

Objective: Several clinical studies have explored the feasibility and efficacy of radiosurgical treatment for mesial temporal lobe epilepsy, but the long-term safety of this treatment has not been fully characterized. This study aims to report and describe radiation-induced cavernous malformation as a delayed complication of radiosurgery in epilepsy patients. Methods: The series includes 20 patients with mesial temporal lobe epilepsy who underwent Gamma Knife radiosurgery (GKRS). The majority received a prescribed isodose of 24 Gy as an adjuvant treatment after anterior temporal lobectomy. Results: In this series, we identified radiation-induced cavernous malformation in three patients, resulting in a cumulative incidence of 18.4% (95% CI, 6.3 to 47.0%) at an eight-year follow-up. These late sequelae of vascular malformation occurred between 6.9 and 7.6 years after GKRS, manifesting later than other delayed radiation-induced changes, such as radiation necrosis. Neurological symptoms attributed to intracranial hypertension were present in those three cases involving cavernous malformation. Of these, two cases, which initially exhibited an insufficient response to radiosurgery, ultimately demonstrated seizure remission following the successful microsurgical resection of the cavernous malformation. Conclusion: All things considered, the development of radiation-induced cavernous malformation is not uncommon in this population and should be acknowledged as a potential long-term complication. Microsurgical resection of cavernous malformation can be preferentially considered in cases where the initial seizure outcome after GKRS is unsatisfactory.

Stereotactic radiosurgery for noncavernous sinus dural arteriovenous fistulas: treatment outcomes and their predictors.

OBJECTIVE: Stereotactic radiosurgery (SRS) has emerged as a safe and effective treatment modality for dural arteriovenous fistulas (dAVFs), particularly cavernous sinus (CS) dAVFs. However, the long-term outcomes of non-CS dAVFs are not well known. This study aimed to evaluate the efficacy and safety of SRS for non-CS dAVFs and to investigate the risk factors for incomplete obliteration. METHODS: Between 2007 and 2020, 65 non-CS dAVFs in 63 patients were treated using SRS at a single institution. Demographic characteristics, initial clinical presentations, clinical outcomes, and radiological findings were retrospectively reviewed. The procedure-related complications were assessed. Radiological outcomes were evaluated as complete obliteration, incomplete obliteration, and angiographic worsening, whereas clinical outcomes were evaluated for symptom recovery. RESULTS: At a median follow-up of 17 months, the overall complete obliteration rate was 63.1%, and the cumulative obliteration rates were 24.6%, 60.0%, 70.0%, and 74.3% at 12, 24, 36, and 48 months, respectively. Six patients underwent retreatment due to angiographic worsening; in 5 of these patients, recruitment of arterial feeders was newly observed in the adjacent sinus, which was not treated in the initial SRS. In the multivariate analysis, high-flow shunt and venous ectasia were associated with incomplete obliteration. No adverse events occurred after SRS. CONCLUSIONS: SRS for non-CS dAVFs is safe, and its efficacy is highly variable according to location. High-flow shunts may indicate greater radioresistance. In the retreated cases, new fistulas tended to be accompanied by sinus steno-occlusion and formed in the adjacent sinus segments.

Surgical Treatment of Prolactinomas: Potential Role as a First-Line Treatment Modality.

PURPOSE: Treatment with dopamine agonists (DAs) has been the first-line standard treatment for prolactinoma, and surgery has been reserved for drug intolerance and resistance for several decades. We evaluated whether surgery plays a primary role in prolactinoma management. MATERIALS AND METHODS: We conducted a retrospective study of 210 prolactinoma patients who had received surgical treatment at our institution. We analyzed the treatment outcomes according to tumor extent, sex, and preoperative DA medication. RESULTS: Overall hormonal remission was achieved in 164 patients (78.1%), and complete removal was achieved in 194 patients (92.4%). When the tumors were completely removed, the remission rate increased to 84.5%. Anterior pituitary function was normalized or improved in 94.6% of patients, whereas only 4.1% of patients showed worsening of hormone control. Hormonal remission was higher in patients who had not received DA preoperatively than in those who had received preoperative DA treatment. Smaller tumor size (<1 cm), no invasion into the cavernous sinus, and female sex were predictors of good surgical outcomes. CONCLUSION: Although DAs remain the first-line standard treatment for prolactinomas, surgery can be an excellent option and should be considered as an alternative primary treatment modality when patients are predicted to achieve a good surgical outcome.

Ulmus davidiana 60% edible ethanolic extract for prevention of pericyte apoptosis in diabetic retinopathy.

Diabetic retinopathy (DR) is a disease that causes visual deficiency owing to vascular leakage or abnormal angiogenesis. Pericyte apoptosis is considered one of the main causes of vascular leakage in diabetic retina, but there are few known therapeutic agents that prevent it. Ulmus davidiana is a safe natural product that has been used in traditional medicine and is attracting attention as a potential treatment for various diseases, but its effect on pericyte loss or vascular leakage in DR is not known at all. In the present study, we investigated on the effects of 60% edible ethanolic extract of U. davidiana (U60E) and catechin 7-O-ß-D-apiofuranoside (C7A), a compound of U. davidiana, on pericyte survival and endothelial permeability. U60E and C7A prevented pericyte apoptosis by inhibiting the activation of p38 and JNK induced by increased glucose and tumor necrosis factor alpha (TNF-α) levels in diabetic retina. Moreover, U60E and C7A reduced endothelial permeability by preventing pericyte apoptosis in co-cultures of pericytes and endothelial cells. These results suggest that U60E and C7A could be a potential therapeutic agent for reducing vascular leakage by preventing pericyte apoptosis in DR.

Fat graft survival requires metabolic reprogramming toward the glycolytic pathway.

BACKGROUND: Fat grafts are widely used as natural fillers in reconstructive and cosmetic surgery. However, the mechanisms underlying fat graft survival are poorly understood. Here, we performed an unbiased transcriptomic analysis in a mouse fat graft model to determine the molecular mechanism underlying free fat graft survival. METHODS: We conducted RNA-sequencing (RNA-seq) analysis in a mouse free subcutaneous fat graft model on days 3 and 7 following grafting (n = 5). High-throughput sequencing was performed on paired-end reads using NovaSeq6000. The calculated transcripts per million (TPM) values were processed for principal component analysis (PCA), unsupervised hierarchically clustered heatmap generation, and gene set enrichment analysis. RESULTS: PCA and heatmap data revealed global differences in the transcriptomes of the fat graft model and the non-grafted control. The top meaningful upregulated gene sets in the fat graft model were related to the epithelial-mesenchymal transition, hypoxia on day 3, and angiogenesis on day 7. Mechanistically, the glycolytic pathway was upregulated in the fat graft model at days 3 (FDR q = 0.012) and 7 (FDR q = 0.084). In subsequent experiments, pharmacological inhibition of the glycolytic pathway in mouse fat grafts with 2-deoxy-D-glucose (2-DG) significantly suppressed fat graft retention rates, both grossly and microscopically (n = 5). CONCLUSIONS: Free adipose tissue grafts undergo metabolic reprogramming toward the glycolytic pathway. Future studies should examine whether targeting this pathway can enhance the graft survival rate.

A High-Fat Diet in the Absence of Obesity Increases Lymphangiogenesis by Inducing VEGF-C in a Murine Lymphedema Model.

BACKGROUND: Many researchers have attempted to induce lymphangiogenesis for the treatment of lymphedema. However, most previous studies had limited clinical usefulness. A high-fat diet (HFD) increases serum ß-hydroxybutyrate (ß-OHB) levels, which can stimulate lymphangiogenesis. The authors hypothesized that an HFD will ameliorate lymphedema through enhanced lymphangiogenesis. METHODS: The effects of ß-OHB on the lymphangiogenic process in human dermal lymphatic endothelial cells were analyzed. A mouse tail lymphedema model was used to evaluate the effects of an HFD on lymphedema. Experimental mice were fed an HFD (45% kcal as fat, 20% as protein, and 35% as carbohydrates) for 4 weeks. Tail volume was measured using the truncated cone formula. Biopsy specimens were taken 6 weeks after surgical induction of lymphedema. RESULTS: In human dermal lymphatic endothelial cells, treatment with 20 mM of ß-OHB increased cell viability ( P = 0.008), cell migration ( P = 0.011), tube formation ( P = 0.005), and VEGF-C mRNA and protein expression ( P < 0.001) compared with controls. HFD feeding decreased tail volume by 14.3% and fibrosis by 15.8% ( P = 0.027), and increased the lymphatic vessel density ( P = 0.022) and VEGF-C protein expression ( P = 0.005) compared with those of operated, standard chow diet-fed mice. CONCLUSIONS: The authors' findings demonstrated that ß-OHB promoted lymphatic endothelial cell function and increased VEGF-C mRNA and protein expression. When mice with tail lymphedema were fed an HFD, volume and fibrosis of the tail decreased. Therefore, the authors' findings suggest that an HFD can be a successful novel dietary approach to treating lymphedema. CLINICAL RELEVANCE STATEMENT: Lymphatic regeneration after vascularized lymph node transfer can be augmented when a high-fat diet is used in conjunction with vascularized lymph node transfer.