FOXO1 reduces tumorsphere formation capacity and has crosstalk with LGR5 signaling in gastric cancer cells.

Gastric cancer (GC) is a major of cause of cancer-related death and is characterized by its heterogeneity and molecular complexity. FOXO1 is a transcription factor that plays a key role in GC growth and metastasis. However, the implication of FOXO1 in GC cell stemness has been elusive. This study, for the first time, demonstrates that FOXO1 regulates GC cell stemness in association with LGR5. FOXO1 expression was significantly lower in GC tumorsphere cells than in adherent GC cells. FOXO1 silencing and overexpression promoted and inhibited the tumorsphere formation capacity of GC cells, respectively. Additionally, there was an inverse correlation between FOXO1 and GC stem cell marker LGR5 in human GC specimens. Further in vitro and in vivo experiments showed that negative crosstalk between these two molecules exists and that LGR5 silencing reversed the FOXO1 shRNA-induced tumorsphere formation even without FOXO1 restoration. Taken together, our results suggest that FOXO1 inhibits the self-renewal capacity of GC cells through interaction with LGR5. Thus, FOXO1/LGR5 signaling pathway may provide a novel targeted therapy for GC.

Fascaplysin Exerts Anti-Cancer Effects through the Downregulation of Survivin and HIF-1α and Inhibition of VEGFR2 and TRKA.

Fascaplysin has been reported to exert anti-cancer effects by inhibiting cyclin-dependent kinase 4 (CDK4); however, the precise mode of action by which fascaplysin suppresses tumor growth is not clear. Here, we found that fascaplysin has stronger anti-cancer effects than other CDK4 inhibitors, including PD0332991 and LY2835219, on lung cancer cells that are wild-type or null for retinoblastoma (RB), indicating that unknown target molecules might be involved in the inhibition of tumor growth by fascaplysin. Fascaplysin treatment significantly decreased tumor angiogenesis and increased cleaved-caspase-3 in xenografted tumor tissues. In addition, survivin and HIF-1α were downregulated in vitro and in vivo by suppressing 4EBP1-p70S6K1 axis-mediated de novo protein synthesis. Kinase screening assays and drug-protein docking simulation studies demonstrated that fascaplysin strongly inhibited vascular endothelial growth factor receptor 2 (VEGFR2) and tropomyosin-related kinase A (TRKA) via DFG-out non-competitive inhibition. Overall, these results suggest that fascaplysin inhibits TRKA and VEGFR2 and downregulates survivin and HIF-1α, resulting in suppression of tumor growth. Fascaplysin, therefore, represents a potential therapeutic approach for the treatment of multiple types of solid cancer.

c-Jun N-terminal kinase activation has a prognostic implication and is negatively associated with FOXO1 activation in gastric cancer.

BACKGROUND: Since the biological function of c-Jun N-terminal kinase (JNK) in gastric cancer remains unclear, we investigated the clinical significance of JNK activation and its association with FOXO1 activation. METHODS: Immunohistochemical tissue array analysis of 483 human gastric cancer specimens was performed, and the results of the immunostaining were quantified. The correlation between JNK activation (nuclear staining for pJNK) and clinicopathological features, the proliferation index, prognosis or FOXO1 inactivation (cytoplasmic staining for pFOXO1) was analyzed. The SNU-638 gastric cancer cell line was used for in vitro analysis. RESULTS: Nuclear staining of pJNK was found in 38 % of the gastric carcinomas and was higher in the early stages of pTNM (P < 0.001). pJNK staining negatively correlated with lymphatic invasion (P = 0.034) and positively correlated with intestinal type by Lauren's classification (P = 0.037), Ki-67-labeling index (P < 0.001), cyclin D1 (P = 0.045), cyclin E (P < 0.001) and pFOXO1 (P < 0.001). JNK activation correlated with a longer patients survival (P =0.008) and patients with a JNK-active and FOXO1-inactive tumor had a higher survival rate than the remainder of the population (P = 0.004). In vitro analysis showed that JNK inhibition by SP600125 in SNU-638 cells decreased cyclin D1 protein expression and increased FOXO1 activation. Further, JNK inhibition markedly suppressed colony formation, which was partially restored by FOXO1 shRNA expression. CONCLUSIONS: Our results indicate that JNK activation may serve as a valuable prognostic factor in gastric cancer, and that it is implicated in gastric tumorigenesis, at least in part, through FOXO1 inhibition.

Loss of FOXO1 promotes gastric tumour growth and metastasis through upregulation of human epidermal growth factor receptor 2/neu expression.

BACKGROUND: The biological significance of FOXO1, a member of the forkhead box O transcription factor family, in gastric cancer (GC) remains unclear. The present study provides direct evidence of the role of FOXO1 in tumour growth and metastasis of GC in relation to human epidermal growth factor receptor 2 (HER2). METHODS: The expressions of FOXO1 and HER2 were modulated in GC cell lines (SNU-638, MKN45, SNU-216 and NCI-N87) by stable transfections. The effects of transfection on GC phenotypes were evaluated in vitro and in animal models. In addition, the relationship between FOXO1 and HER2 was analysed using GC clinical specimens, cell lines and xenografts. RESULTS: FOXO1 silencing in GC cells increased colony formation and mesenchymal transition in vitro, as well as tumour growth and metastasis in nude mice, whereas HER2 silencing induced the opposite results.. Furthermore, an inverse relationship between FOXO1 and HER2 was found in clinical specimens of GC, GC cells and GC xenograft tumours. Although a negative crosstalk between these two molecules was shown, double knockdown of both FOXO1 and HER2 in GC cells revealed that HER2 silencing reversed the FOXO1 shRNA-induced migration and invasion even without the FOXO1 restoration. CONCLUSIONS: Our results indicate that loss of FOXO1 promotes GC growth and metastasis by upregulating HER2 expression and that the HER2 expression is more critical to the induction of GC cell metastasis. The present study provides evidence that the FOXO1/HER2 pathway may regulate GC progression in a subgroup of GC patients.

The forkhead transcription factor FOXO1 mediates cisplatin resistance in gastric cancer cells by activating phosphoinositide 3-kinase/Akt pathway.

BACKGROUND: Cisplatin (CDDP) is one of the most important chemotherapeutic agents in the treatment of advanced gastric cancer, but its efficacy is limited by CDDP resistance. Because the transcription factor FOXO1 is related to chemoresistance in various cancer cells, we investigated the function of FOXO1 in CDDP resistance in human gastric cancer cells. METHODS: Human gastric cancer cell lines MKN45 and SNU-601 were used. FOXO1 activation was modulated by transfection of FOXO1 AAA mutant gene or FOXO1 shRNA. The effects of FOXO1 on cell growth and CDDP cytotoxicity were assessed by crystal violet assay. Protein expressions of FOXO1, p110α, pAkt, and Akt were analyzed by Western blotting, and FOXO1 mRNA expression was evaluated by semiquantitative reverse transcription-polymerase chain reaction. FOXO1 activity was determined by luciferase reporter assay, and cell apoptosis was assessed by DAPI staining and Western blotting for PARP cleavage. RESULTS: Cisplatin treatment induced FOXO1 expression and activation in both gastric cancer cell lines. FOXO1 overexpression increased the CDDP resistance without changes in cell growth, whereas FOXO1 silencing enhanced CDDP cytotoxicity along with apoptotic characteristics. Both constitutive and CDDP-induced FOXO1 activations were accompanied by an increase in p110α and pAkt expression. Furthermore, Akt inhibition by LY294002 treatment restored the CDDP cytotoxicity that was suppressed by FOXO1 overexpression. CONCLUSION: FOXO1 inhibits CDDP-induced apoptosis in gastric cancer cells via activating PI3K/Akt pathway. Thus, FOXO1 may be an useful pharmacological indicator to predict CDDP efficacy in gastric cancer treatment.

Trends in degenerative lumbar spinal surgery during the early COVID-19 pandemic in Republic of Korea: A national study utilizing the national health insurance database.

During the first year of the COVID-19 pandemic, the Republic of Korea (ROK) experienced three epidemic waves in February, August, and November 2020. These waves, combined with the overarching pandemic, significantly influenced trends in spinal surgery. This study aimed to investigate the trends in degenerative lumbar spinal surgery in ROK during the early COVID-19 pandemic, especially in relation to specific epidemic waves. Using the National Health Information Database in ROK, we identified all patients who underwent surgery for degenerative lumbar spinal diseases between January 1, 2019 and December 31, 2020. A joinpoint regression was used to assess temporal trends in spinal surgeries over the first year of the COVID-19 pandemic. The number of surgeries decreased following the first and second epidemic waves (p<0.01 and p = 0.34, respectively), but these were offset by compensatory increases later on (p<0.01 and p = 0.05, respectively). However, the third epidemic wave did not lead to a decrease in surgical volume, and the total number of surgeries remained comparable to the period before the pandemic. When compared to the pre-COVID-19 period, average LOH was reduced by 1 day during the COVID-19 period (p<0.01), while mean hospital costs increased significantly from 3,511 to 4,061 USD (p<0.01). Additionally, the transfer rate and the 30-day readmission rate significantly decreased (both p<0.01), while the reoperation rate remained stable (p = 0.36). Despite the impact of epidemic waves on monthly surgery numbers, a subsequent compensatory increase was observed, indicating that surgical care has adapted to the challenges of the pandemic. This adaptability, along with the stable total number of operations, highlights the potential for healthcare systems to continue elective spine surgery during public health crises with strategic resource allocation and patient triage. Policies should ensure that surgeries for degenerative spinal diseases, particularly those not requiring urgent care but crucial for patient quality of life, are not unnecessarily halted.

The efficacy of therapeutic hypothermia in patients with poor-grade aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

BACKGROUND: This study evaluates the effectiveness of Therapeutic Hypothermia (TH) in treating poor-grade aneurysmal subarachnoid hemorrhage (SAH), focusing on functional outcomes, mortality, and complications such as vasospasm, delayed cerebral ischemia (DCI), and hydrocephalus. METHODS: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a comprehensive literature search was conducted across multiple databases, including Medline, Embase, and Cochrane Central, up to November 2023. Nine studies involving 368 patients were selected based on eligibility criteria focusing on TH in poor-grade SAH patients. Data extraction, bias assessment, and evidence certainty were systematically performed. RESULTS: The primary analysis of unfavorable outcomes in 271 participants showed no significant difference between the TH and standard care groups (risk ratio [RR], 0.87). However, a significant reduction in vasospasm was observed in the TH group (RR, 0.63) among 174 participants. No significant differences were found in DCI, hydrocephalus, and mortality rates in the respective participant groups. CONCLUSIONS: TH did not significantly improve primary unfavorable outcomes in poor-grade SAH patients. However, the reduction in vasospasm rates indicates potential specific benefits. The absence of significant findings in other secondary outcomes and mortality highlights the need for further research to better understand TH's role in treating this patient population.

A synergistic interaction between transcription factors nuclear factor-κB and signal transducers and activators of transcription 3 promotes gastric cancer cell migration and invasion.

BACKGROUND: The transcription factor nuclear factor-κB (NF-κB) has been implicated in gastric cancer metastasis, but the underlying molecular mechanisms remain unclear. We investigated the role of the interaction between NF-κB and signal transducers and activators of transcription 3 (STAT3) in controlling metastatic potential of gastric cancer cells. METHODS: Immunohistochemistry for NF-κB p65 (RelA), phospho-Tyr705-STAT3 (pSTAT3), or matrix metalloproteinase 9 (MMP9) was performed on tissue array slides containing 255 gastric carcinoma specimens. NF-κB inhibition in SNU-638 and MKN1 gastric cancer cell lines were performed by transduction with a retroviral vector containing NF-κB repressor mutant of IκBα, and STAT3 was silenced by RNA interference. We also did luciferase reporter assay, double immunofluorescence staining and immunoblotting. Cell migration and invasion were determined by wound-healing assay and invasion assay, respectively. RESULTS: NF-κB and STAT3 were constitutively activated and were positively correlated (P=0.038) in gastric cancer tissue specimens. In cell culture experiments, NF-κB inhibition reduced STAT3 expression and activation, whereas STAT3 silencing did not affect NF-κB activation. Moreover, both NF-κB inhibition and STAT3 silencing decreased gastric cancer cell migration and invasion in a synergistic manner. In addition, both NF-κB activation and STAT3 activation were positively correlated with MMP9 in gastric cancer tissues (P=0.001 and P=0.022, respectively), decreased E-cadherin expression and increased Snail and MMP9 expressions in cultured cells. CONCLUSION: NF-κB and STAT3 are positively associated and synergistically contribute to the metastatic potential of gastric cancer cells. Thus, dual use of NF-κB and STAT3 inhibitors may enhance the efficacy of the anti-metastatic treatment of gastric cancer.

Iatrogenic mixed pial and dural arteriovenous fistula after pterional approach for surgical clipping of aneurysm: A case report.

Craniotomy is known as a cause of iatrogenic dural cerebral arteriovenous fistula (AVF). However, mixed pial and dural AVFs after craniotomy are extremely rare and require accurate diagnosis and prompt treatment due to their aggressiveness. We present a case of an iatrogenic mixed pial and dural AVF diagnosed 2 years after pterional craniotomy for surgical clipping of a ruptured anterior choroidal aneurysm. The lesion was successfully treated using single endovascular procedure of transvenous coil embolization through the engorged vein of Labbe and the superficial middle cerebral vein. The possibility of the AVF formation after the pterional approach should always be kept in mind because it usually occurs at the middle cranial fossa, which frequently has an aggressive nature owing to direct cortical venous or leptomeningeal drainage patterns. This complication is believed to be caused by angiogenetic conditions due to coagulation, retraction, and microinjuries of the perisylvian vessels, and can be prevented by performing careful sylvian dissection according to patient-specific perisylvian venous anatomy.

Predictive Factors of Recurrence after Endovascular Treatment of Unruptured Vertebrobasilar Fusiform Aneurysms.

PURPOSE: This study aimed to investigate the predictive factors of recurrence after endovascular treatment (EVT) for unruptured vertebrobasilar fusiform aneurysms (VBFA). METHODS: This single-center retrospective study evaluated 36 patients who underwent EVT of unruptured VBFA between 2008 and 2020. Variables influencing recurrence, such as size, type, thrombus, preoperative symptoms, and treatment methods, were analyzed. All patients were followed up using vessel imaging. RESULTS: In total, 7 of 36 patients (19.4%) developed recurrence. The mean time from EVT to recurrence was 9.2 months (range 2-26.9 months). Maximum aneurysmal diameter on magnetic resonance imaging was decreased, increased, and remained unchanged in 1, 7, and 28 patients, respectively. Transitional type VBFA, brain compression symptoms, large aneurysmal diameter and length, preoperative modified Rankin Scale (mRS) score ≥ 2, sole stenting technique, and intra-aneurysmal thrombus significantly influenced the risk of recurrence. Post-EVT, 7 (19.4%) patients showed complete occlusion of the aneurysm on the immediate postoperative angiogram, and 22 (61.1%) patients showed complete occlusion on the 1­year follow-up imaging. Good outcomes were observed in 32 patients (88.9%) at the last follow-up, with a mRS score of 0-1 after EVT. CONCLUSION: EVT achieves good outcomes in unruptured VBFA. Transitional type VBFA, brain compression symptoms, large aneurysmal diameter and length, preoperative mRS score ≥ 2, sole stenting technique, and intra-aneurysmal thrombus are risk factors for aneurysm recurrence after EVT.

Efficacy of 3D-printed simulation models of unruptured intracranial aneurysms in patient education and surgical simulation.

OBJECTIVE: The purpose of this study was to determine the efficacy of a 3D-printed aneurysm simulation model (3DPM) in educating patients and improving physicians' comprehension and performance. METHODS: This prospective study involved 40 patients who were diagnosed with unruptured intracranial aneurysms (UIAs) and scheduled for surgical clipping or endovascular coiling and randomly divided into two groups (the 3DPM group and the non-3DPM group). The 3DPM was used in preoperative consultation with patients and intraoperatively referenced by surgeons. The patients, 7 neurosurgical residents, and 10 surgeons completed questionnaires (5-point Likert scale) to determine the usefulness of the 3DPM. RESULTS: Patients in the 3DPM group had significantly higher scores in terms of their understanding of the disease (mean 4.85 vs. 3.95, p<0.001) and the treatment plan (mean 4.85 vs. 4.20, p=0.005) and reported higher satisfaction during consultation (5.0 vs. 4.60, p=0.036) than patients in the non-3DPM group. During patient consultation, 3DPMs were most useful in improving doctor-patient communication (mean 4.57, range 4-5). During clipping surgery, the models were most useful in assessing adjacent arteries (mean 4.9, range 4-5); during endovascular coiling, they were especially helpful in microcatheter shaping (mean 4.7, range 4-5). CONCLUSIONS: In general, 3DPMs are beneficial in educating patients and improving the physician's performance in terms of surgical clipping and endovascular coiling of UIAs.

Breast Cancer to Meningioma: A Rare Case of Tumor-to-Tumor Metastasis.

Tumor-to-tumor metastasis (TTM) is defined as the hematogenous metastasis within a primary host tumor from a donor neoplasm. Since there is insufficient evidence regarding the pathophysiology, clinical course, and management of TTM, there are no precise guidelines for its management. A 73-year-old female patient diagnosed with breast cancer was found to have convexity meningioma. Since the size of tumor and peritumoral brain edema increased during follow-up period, the meningioma was treated with surgical resection. Postoperatively, histopathologic examination confirmed metastasis of invasive ductal carcinoma within a secretory meningioma. The final diagnosis was TTM of breast cancer in meningioma. Here, we report a rare case of intra-meningioma metastasis and a review of literature to provide a better understanding of this rare phenomenon.

The significance of evaluating sphenoid sinus fluid by postmortem computed tomography in cases of drowning.

PURPOSE: In cases of drowning, the presence of sphenoid sinus fluid is a non-specific autopsy finding. However, studies have reported that fluid accumulation in the paranasal sinuses is more commonly observed in drowning victims. Furthermore, some laboratory tests, such as diatom and electrolyte analysis, can serve as supplementary diagnostic tools for diagnosing drowning. Therefore, accurate sphenoid sinus fluid sampling is an important aspect of an autopsy in suspected drowning cases. The aim of this study was to identify the significance of evaluating sphenoid sinus fluid by PMCT images in cases of drowning. METHODS: We retrospectively reviewed 54 drowning victims who underwent PMCT and forensic autopsy. Fluid volume in the sphenoid sinus was measured using a graduated syringe during autopsy and a three-dimensional (3D) workstation based on PMCT images was used for the purpose of comparison. The Mann-Whitney U test and Spearman's rank correlation coefficient was used to evaluate statistically significant differences and correlations. Additionally, a Bland-Altman plot was employed to assess the agreement between PMCT and autopsy. RESULTS: The median volume was 1.65 (range 0.00-12.4) ml and 1.55 (range 0.00-7.00) ml in the PMCT and autopsy, respectively, showing a statistically insignificant difference (p = 0.294) and a significant correlation (Rs = 0.896). In 35 cases, the PMCT overestimated the fluid volume more than the autopsy, whereas in 14 cases, the PMCT underestimated the fluid volume. No fluid was identified in seven cases during the autopsy, whereas in five patients, no fluid was found in both PMCT and autopsy. By analyzing the Bland-Altman plot, a bias of 0.73 ± 1.4 ml and limits of agreement ranging from -2.04 to 3.51 ml were observed for sphenoid sinus fluid volume measurements. CONCLUSIONS: Based on the limitations of traditional fluid volume measurement in the sphenoid sinus during autopsy, we propose the utilization of PMCT volumetric analysis prior to autopsy as a means to enhance the detection of sphenoid sinus fluid in cases of drowning.

Fusion Assessment of Oblique Lumbar Interbody Fusion Using Demineralized Bone Matrix: A 2-Year Prospective Study.

OBJECTIVE: Although several studies have reported successful fusion rates after oblique lumbar interbody fusion (OLIF) using allografts or dimerized bone matrix (DBM) instead of autografts, whether OLIF can achieve satisfactory solid fusion without the use of autografts remains unclear. This study investigated the real fusion rates after OLIF using allografts and DBM, which were evaluated using both dynamic radiographs and computed tomography scans. METHODS: We enrolled 79 consecutive patients who underwent minimally invasive OLIF followed by percutaneous pedicle screw fixation. All patients were treated with OLIF between L2 and L5 and underwent radiographic and clinical follow-ups at 12, 18, and 24 months after surgery. Radiographic assessment of fusion was performed using the modified BrantigaSteffee-Fraser (mBSF) scale, which was categorized as follows: grades I (radiographic pseudoarthrosis), II (indeterminate fusion), and III (solid radiographic fusion). Other radiologic and clinical outcomes were evaluated using the following parameters: vertebral slippage distance, disc height, subsidence, Oswestry Disability Index (ODI), and visual analogue scale (VAS). RESULTS: Clinical outcomes demonstrated significant improvements in the VAS scores for back pain, leg pain, and ODI after surgery. Subsidence was present in 34 cases (35.4%) at 12 months postoperatively, which increased to 47.9% and reached 50.0% at 1.5 years and 2 years after surgery, respectively. The solid fusion rate after OLIF was 32.3% at 1 year, increased to 58.3% at 1.5 years, and reached 72.9% at 2 years. Radiographic pseudoarthrosis was 24.0% at 1 year, which decreased to 6.3% at 1.5 years and 3.1% at 2 years. CONCLUSION: OLIF is a safe and effective surgical procedure for the treatment of degenerative lumbar diseases. The mBSF scale, which simultaneously evaluates both dynamic angles and bone bridge formation, offers great reliability for the radiological assessment of fusion. Moreover, OLIF using allografts and DBM, which is performed on one or 2 levels at L2-5, can achieve satisfactory fusion rates within 2 years after surgery.

Does the Surgical Approach Matter in Treating Odontoid Fractures? A Comparison of Mechanical Complication Rates Between Anterior Versus Posterior Surgical Approaches: A Meta-Analysis and Systematic Review.

Objective: Odontoid fractures are treated surgically through the anterior or posterior approach. Each surgical approach has its advantages and disadvantages, so the preferred approach remains debatable. There are few meta-analyses or systemic reviews on the mechanical complications of surgical treatment for odontoid fractures. This meta-analysis aimed to compare the operation-related morbidity, including mechanical complications, and mortality of patients with odontoid fractures, treated via the anterior or posterior approach. Methods: A systematic search was performed on PubMed/Medline, Embase, and the Cochrane Library for the studies up to October 2023 on the complication rate of the surgical treatment of odontoid fractures, related to the surgical approach. The risk ratios (RR) with the 95% confidence intervals (CIs) were pooled to assess the mechanical complication rates, other complications, revision surgery, and mortality, depending on the surgical approach. Results: A total of 1,519 studies were retrieved using the search strategy, and 782 patients from 15 articles were included in this meta-analysis. Mechanical complications were significantly more frequent in the anterior surgical group with low heterogeneity. The incidences of fracture nonunion and revision surgery were also higher in the anterior surgery group. However, there was no significant difference in systemic complications and mortality rates between the two groups. Conclusion: The posterior approach was more advantageous than the anterior approach in terms of mechanical complications, fusion rates, and incidence of revision surgery. However, further studies, should be performed to strengthen these results.

Surgical treatment of spondylolisthesis by oblique lumbar interbody fusion and transpedicular screw fixation: Comparison between conventional double position versus navigation-assisted single lateral position.

BACKGROUND AND OBJECTIVES: Oblique lumbar interbody fusion (OLIF) procedures involve anterior insertion of interbody cage in lateral position. Following OLIF, insertion of pedicle screws and rod system is performed in a prone position (OLIF-con). The location of the cage is important for restoration of lumbar lordosis and indirect decompression. However, inserting the cage at the desired location is difficult without reduction of spondylolisthesis, and reduction after insertion of interbody cage may limit the amount of reduction. Recent introduction of spinal navigation enabled both surgical procedures in one lateral position (OLIF-one). Therefore, reduction of spondylolisthesis can be performed prior to insertion of interbody cage. The objective of this study was to compare the reduction of spondylolisthesis and the placement of cage between OLIF-one and OLIF-con. METHODS: We retrospectively reviewed 72 consecutive patients with spondylolisthesis for this study; 30 patients underwent OLIF-one and 42 underwent OLIF-con. Spinal navigation system was used for OLIF-one. In OLIF-one, the interbody cage was inserted after reducing spondylolisthesis, whereas in OLIF-con, the cage was inserted before reduction. The following parameters were measured on X-rays: pre- and postoperative spondylolisthesis slippage, reduction degree, and the location of the cage in the disc space. RESULTS: Both groups showed significant improvement in back and leg pains (p < .05). Transient motor or sensory changes occurred in three patients after OLIF-con and in two patients after OLIF-one. Pre- and postoperative slips were 26.3±7.7% and 6.6±6.2% in OLIF-one, and 23.1±7.0% and 7.4±5.8% in OLIF-con. The reduction of slippage was 74.4±6.3% after OLIF-one and 65.4±5.7% after OLIF-con, with a significant difference between the two groups (p = .04). The cage was located at 34.2±8.9% after OLIF-one and at 42.8±10.3% after OLIF-con, with a significant difference between the two groups (p = .004). CONCLUSION: Switching the sequence of surgical procedures with OLIF-one facilitated both the reduction of spondylolisthesis and the placement of the cage at the desired location.

Roles of NF-κB activation in benign prostatic hyperplasia and association between NF-κB and HIF-1α.

OBJECTIVE: The aim of this study was to elucidate the role of NF-κB activation in benign prostatic hyperplasia (BPH) using immunohistochemistry. METHODS: Immunohistochemical staining for NF-κB was performed and evaluated, dividing into glands and stroma in 101 human BPH tissues. To evaluate the impacts of NF-κB activation on BPH progression, correlations between NF-κB expression and clinical findings, hormone receptors, and HIF-1α were evaluated. RESULTS: NF-κB expression was found in 37.6% and 30.7% in glands and stroma of BPH, respectively. Total and T-zone volumes in transrectal ultrasonography were significantly higher in patients with NF-κB activation than those without NF-κB activation in the stroma. However, NF-κB activation of stroma was not correlated with HIF-1α expression and microvessel density. In subgroup analysis based on NF-κB activation, androgen and progesterone receptors of stroma were highly expressed in HIF-1α negative cases than in HIF-1α positive cases. In cases without NF-κB activation, patients with HIF-1α positivity showed a high frequency of diffuse fibrosis than those with HIF-1α negativity (P = 0.001). CONCLUSION: Taken together, our result showed that NF-κB activation of stroma was significantly correlated with low total and T-zone volumes in transrectal ultrasonography. Diffuse fibrosis was frequently found in patients with NF-κB inactivation and HIF-1α positivity.

Evaluation of Stent Apposition in the LVIS Blue Stent-Assisted Coiling of Distal Internal Carotid Artery Aneurysms : Correlation with Clinical and Angiographic Outcomes.

OBJECTIVE: To evaluate the stent apposition of a low-profile visualized intraluminal support (LVIS) device in distal internal carotid artery (ICA) aneurysms, examine its correlation with clinical and angiographic outcomes, and determine the predictive factors of ischemic adverse events (IAEs) related to stent-assisted coiling. METHODS: We retrospectively analyzed a prospectively maintained database of 183 patients between January 2017 and February 2020. The carotid siphon from the cavernous ICA to the ICA terminus was divided into posterior, anterior, and superior bends. The anterior bends were categorized into angled (V) and non-angled (C, U, and S) types depending on the morphology and measured angles. Complete stent apposition (CSA) and incomplete stent apposition (ISA) were evaluated using unsubtracted angiography and flat-panel detector computed tomography. Dual antiplatelet therapy with aspirin 200 mg and clopidogrel 75 mg was administered. Clopidogrel resistance was defined as fewer responders (≥10%, <40%) and non-responders (<10%) based on the percent inhibition (%INH) of the VerifyNow system. These were counteracted by a dose escalation to 150 mg for fewer responders or substitution with cilostazol 200 mg for non-responders. IAEs included intraoperative in-stent thrombosis, transient ischemic attack, cerebral infarction, and delayed in-stent stenosis. A multivariate logistic regression analysis was used to determine the predictive factors for ISA and IAEs. RESULTS: There were 33 ISAs (18.0%) and 27 IAEs (14.8%). The anterior bend angle was narrower in ISA (-4.16°±25.18°) than in CSA (23.52°±23.13°) (p<0.001). The V- and S-types were independently correlated with the ISA (p<0.001). However, treatment outcomes, including IAEs (15.3% vs. 12.1%), aneurysmal complete occlusion (91.3% vs. 88.6%), and recanalization (none of them), did not differ between CSA and ISA (p>0.05). The %INH of 27 IAEs (13.78%±14.78%) was significantly lower than that of 156 non-IAEs (26.82%±20.23%) (p<0.001). Non-responders to clopidogrel were the only significant predictive factor for IAEs (p=0.001). CONCLUSION: The angled and tortuous anatomical peculiarity of the carotid siphon caused ISA of the LVIS device; however, it did not affect clinical and angiographic outcomes, while the non-responders to clopidogrel affected the IAEs related to stent-assisted coiling.

The Modified 11-Item Frailty Index and Postoperative Outcomes in Patients Undergoing Lateral Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to analyze postoperative complications and recovery patterns in different modified 11-item frailty index (mFI-11) groups after lateral lumbar interbody fusion (LLIF) surgery. SUMMARY OF BACKGROUND DATA: The relationship between the mFI-11 score and LLIF surgery has not been previously reported. METHODS: A single-center, consecutive series of patients who underwent LLIF with at least two years of follow-up were retrospectively reviewed. Complications after LLIF surgery were recorded. Clinical outcomes, including the visual analog scale (VAS) for back/leg pain and the Oswestry Disability Index (ODI), were evaluated preoperatively and at 1 and 2 years postoperatively. The proportions of patients who achieved substantial clinical benefit (SCB) for the VAS-B, VAS-L, and ODI were also analyzed. RESULTS: One hundred fifty-two patients included in the present study were grouped according to their mFI-11 score: 0 (n = 39), 0.09 (n = 69), 0.18 (n = 31), and ≥0.27 (n = 13). An mFI-11 score ≥0.27 was a significant predictor of urinary complications (adjusted odds ratio: 3.829, P = 0.013). At 2 years postoperatively, patients in all frailty categories experienced improvements in the VAS for back pain, VAS for leg pain, and ODI, without significant differences between the four groups (p = 0.182, 0.121, and 0.804, respectively). There were also no significant differences in the proportions of patients achieving SCB for back/leg pain and the ODI between the four groups (P = 0.843, 0.957, and 0.915, respectively). CONCLUSION: An mFI-11 score was found to be independently associated with urologic complications in patients who underwent LLIF. Patients in all frailty categories experienced significant improvements in back pain, leg pain, and the ODI at 1 year and 2 years postoperatively. LLIF surgery may be useful for patients with high frailty index.Level of Evidence: 4.

Rapid-Growing Intracranial Immature Teratoma Presenting Obstructive Hydrocephalus and Abducens Nerve Palsy: A Case Report and Literature Review.

Intracranial immature teratoma is an extremely rare disease with poor prognosis and requires complicated treatment. Owing to the deep midline location of the tumor, total surgical resection of the tumor is challenging. We present our experience with a fast-growing pineal gland immature teratoma in a 4-year-old boy, who presented with obstructive hydrocephalus and abducens nerve palsy, which was treated with total surgical resection of the tumor. In addition, we aimed to determine the appropriate treatment modality for intracranial immature teratomas by reviewing the literature and investigating the prognosis.