Surgical treatment of a giant paraophthalmic aneurysm postfailed flow diversion through endoscopic endonasal approach: Technical nuances and review of the literature.

Background: Giant internal carotid artery (ICA) aneurysms are usually treated through flow diversion, coiling, or a combination of both. However, certain cases that fail the endovascular treatment pose a technical challenge. Case Description: A 68-year-old male presented with gradual visual changes affecting his right eye and was found to have a giant unruptured right paraophthalmic aneurysm. The aneurysm showed growth, and the patient's symptoms worsened despite coiling and flow diversion. Due to the location of this aneurysm and persistent compression of the optic chiasm by the coil mass, his right ICA was sacrificed, and an expanded endoscopic endonasal approach was successfully used to clip the residual aneurysm, remove the coil mass, and thus, decompress the optic chiasm. The patient's visual symptoms improved after that, and post clipping imaging demonstrated adequate occlusion of his right paraophthalmic aneurysm. Conclusion: Recognizing the option of an endoscopic endonasal approach for clipping giant internal carotid aneurysms is of great importance. This approach can be safe and technically successful for the treatment of paraophthalmic aneurysms that fail the typical endovascular treatment.

Tumor Suppressor MicroRNAs in Clinical and Preclinical Trials for Neurological Disorders.

Cancers and neurological disorders are two major types of diseases in humans. We developed the concept called the "Aberrant Cell Cycle Disease (ACCD)" due to the accumulating evidence that shows that two different diseases share the common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncoprotein activation and tumor suppressor (TS) inactivation, which are associated with both tumor growth in cancers and neuronal death in neurological disorders. Therefore, some cancer therapies (e.g., kinase/oncogene inhibition and TS elevation) can be leveraged for neurological treatments. MicroRNA (miR/miRNA) provides a new style of drug-target binding. For example, a single tumor suppressor miRNA (TS-miR/miRNA) can bind to and decrease tens of target kinases/oncogenes, producing much more robust efficacy to block cell cycle re-entry than inhibiting a single kinase/oncogene. In this review, we summarize the miRNAs that are altered in both cancers and neurological disorders, with an emphasis on miRNA drugs that have entered into clinical trials for neurological treatment.

Can hospitalists improve COVID-19 vaccination rates?

Three years after the start of the SARS-CoV-2 virus (COVID-19) pandemic, its effects continue to affect society and COVID-19 vaccination campaigns continue to be a topic of controversy and inconsistent practice. After experiencing spikes in COVID-19 cases, our University of California Davis Health Division of Hospital Medicine sought to understand the reasons underlying the low COVID-19 vaccination rates in our county and find approaches to improve the number of vaccinations among adults admitted to the inpatient setting. This quality improvement project aimed to increase COVID-19 primary and booster vaccine efforts through a multi-pronged approach of increased collaboration with specialised staff and optimisation of use of our electronic health record system.Our key interventions focused on developing a visual reminder of COVID-19 vaccine status using the functionality of our electronic medical record (EMR), standardising documentation of COVID-19 vaccine status and enhancing team-based vaccination discussions through team huddles and partnering with inpatient care coordinators. While our grassroots approach enhanced COVID-19 vaccination rates in the inpatient setting and had additional benefits such as increased collaboration among teams, system-level efforts often made a greater impact at our healthcare centre. For other institutions interested in increasing COVID-19 vaccination rates, our top three recommendations include integrating vaccination into pre-existing workflows, optimising EMR functionality and increasing vaccine accessibility in the inpatient setting.

The Lipidomic Signature of Glioblastoma: A Promising Frontier in Cancer Research.

Glioblastoma is the most aggressive primary brain malignancy in adults, and has a survival duration of approximately 15 months. First line treatment involves surgical resection, chemotherapy, and radiation, but despite the multi-pronged approach and advances in cancer research, glioblastoma remains devastating with a high mortality rate. Lipidomics is an emerging discipline that studies lipid pathways and characteristics, and is a promising field to understand biochemical mechanisms. In glioblastoma, disrupted lipid homeostasis has been reported in the literature. A thorough understanding of serum lipidomics may offer ways to better understand glioblastoma biomarkers, prognosis, and treatment options. Here, we review the literature, offering future directions for lipidomics research in glioblastomas.

Promising response to vemurafenib and cobimetinib treatment for BRAF V600E mutated craniopharyngioma: a case report and literature review.

Craniopharyngiomas are tumors that arise from the remnants of Rathke's pouch along the nasopharynx to the diencephalon. Current standard of care includes maximal surgical resection versus adjuvant radiation if a maximal resection is unfeasible. Pharmacological therapy with MAPK targeted agents is an emerging therapeutic option for tumors with BRAF V600E mutations. We report a 45-year-old male with a strictly third ventricle papillary craniopharyngioma with a BRAF V600E mutation. After initial surgery with subtotal resection, the patient demonstrated durable response to targeted BRAF and MEK inhibitor therapy with vemurafenib and cobimetinib. Our report suggests that targeted therapy may reduce the need for radiation and impact surgical interventions in select cases.

Cosmetic Outcomes of Supraorbital Keyhole Craniotomy Via Eyebrow Incision: A Systematic Review and Meta-Analysis.

Background Supraorbital eyebrow craniotomy is a minimally invasive alternative to a frontotemporal craniotomy and is often used for tumor and vascular pathologies. The purpose of this study was to investigate how patient cosmetic outcomes are affected by technique variations of this approach. Methods PubMed, Embase, and Scopus databases were systematically searched, and results were reported according to PRISMA guidelines. For the meta-analysis portion, the DerSimonian-Laird random effects model was used, and the primary end points were patient satisfaction and percentage of permanent cosmetic complications. Results A total of 2,629 manuscripts were identified. Of those, 124 studies (8,241 surgical cases) met the inclusion criteria. Overall, 93.04 ± 11.93% of patients reported favorable cosmetic outcome following supraorbital craniotomy, and mean number of cases with permanent cosmetic complications was 6.62 ± 12.53%. We found that vascular cases are associated with more favorable cosmetic outcomes than tumor cases ( p = 0.0001). Addition of orbital osteotomy or use of a drain is associated with adverse cosmetic outcomes ( p = 0.001 and p = 0.0001, respectively). The location of incision, size of craniotomy, utilization of an endoscope, method of cranial reconstruction, skin closure, use of antibiotics, and addition of pressure dressing did not significantly impact cosmetic outcomes ( p > 0.05 for all). Conclusions Supraorbital craniotomy is a minimally invasive technique associated with generally high favorable cosmetic outcomes. While certain techniques used in supraorbital keyhole approach do not pose significant cosmetic risks, utilization of an orbital osteotomy and the addition of a drain correlate with unfavorable cosmetic outcomes.

Trends in successfully matched neurosurgery residency applicants.

OBJECTIVE: The United States Medical Licensing Examination (USMLE) Step 1 recently transitioned to a pass/fail outcome, renewing interest in how programs select neurosurgical residents. This study investigates the association between match status and key academic metrics over time. METHODS: Data are from the National Resident Matching Program from 2009 to 2022 for matched and unmatched US allopathic (MD) seniors. Investigated metrics included the mean number of contiguous ranks; mean number of distinct specialties ranked; mean USMLE Step 1 and Step 2 Clinical Knowledge (CK) scores; mean number of abstracts, presentations, and publications; mean number of research, work, and volunteer experiences; Alpha Omega Alpha status; attendance at a top 40 NIH-funded institution; PhD degree; and other degree. Multiple linear regression without an interaction term was used to evaluate how these have varied between the two groups during the study period and whether there is a difference between unmatched and matched MD seniors applying for a neurosurgical residency. Multiple linear regression with an interaction term was then used to test whether the difference in variables between the two groups changed over time. RESULTS: Regardless of match status, MD senior neurosurgical residency applicants exhibited an increase in USMLE Step 1 and 2 scores; average research experiences; abstracts, presentations, and publications; and work and volunteer experiences (p < 0.001). The percentage of applicants from a top 40 NIH-funded school decreased (p = 0.018), and the percentage who held an additional degree increased (p = 0.007). Between groups, there were significant differences in all categories except work experiences and other degree obtained. Over time, the difference between USMLE Step 2 scores between matched and unmatched seniors diminished (p = 0.027); in contrast, the difference in abstracts, presentations, and publications between the two groups increased over time (p < 0.001). CONCLUSIONS: From 2009 to 2022, neurosurgical residency applicants grew in their achievements across many metrics. In the advent of Step 1 becoming pass/fail, this study suggests that Step 2 is not viewed by programs as an adequate replacement. However, the Step 1 grading transition may serve as an opportunity for other factors to be considered that may better predict success in neurosurgical residency.

External carotid artery-radial artery-vertebral artery bypass for surgical treatment of radiculopathy caused by an extracranial vertebral artery aneurysm: A case report and review of the literature.

Background: Vertebral artery (VA) aneurysm is a rare etiology of cervical radiculopathy and there is a paucity of case reports described in the literature. Case Description: We describe a case of a patient with no history of trauma presenting with a large right VA aneurysm at the C5-C6 level compressing the C6 nerve root and causing a painful radiculopathy. The patient underwent successful external carotid artery-radial artery-VA bypass followed by trapping of the aneurysm and decompression of the C6 nerve root. Conclusion: VA bypass is an effective tool for treatment of symptomatic large extracranial VA aneurysms and a rare cause of radiculopathy.

H3G34-mutant diffuse hemispheric glioma with osseous metastases: a case report and literature review.

Aim: H3G34 diffuse hemispheric glioma is a CNS tumor that is difficult to diagnose and treat and accompanied with poor prognosis. It is becoming clear that extra CNS metastasis may present in a subset of patients with H3G34 gliomas, further complicating diagnosis and treatment. Materials & methods: We present a case of a 19-year-old female with a H3G34 mutant diffuse hemispheric glioma with osseous metastases. We then provide a literature review of the most recent understanding of H3G34 mutant malignancies. Conclusion: Given the stress that patients with H3G34 can experience and the poor prognosis, it is imperative to expand our knowledge and ascertain accurate diagnostic methodologies and targeted therapeutic approaches.

Metabolomics in High Grade Gliomas.

Gliomas are central nervous system (CNS) cancers that are challenging to treat due to their high proliferation and mutation rates. High grade gliomas include grade 3 and grade 4 tumors, which characteristically have a poor prognosis despite advancements in diagnostic methods and therapeutic options. Advances in metabolomics are resulting in more insight as to how cancer modifies the metabolism of the cell and surrounding tissue. Hence, this avenue of research may also emerge as a way to precisely target metabolites unique to gliomas. These biomarkers may provide opportunities for glioma diagnosis, prognosis and future therapeutic intervention. In this review, we harvest the literature that highlights notable biomolecules in high grade gliomas and promising therapeutic targets and interventions.

High systemic immune-inflammation index represents an unfavorable prognosis of malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) represents a fatal disease with high aggressiveness, and limited biomarkers have yet been identified for MPM. The present study aims to explore potential serum prognostic factors of MPM. Materials and methods: A retrospective analysis of 97 pathologically diagnosed MPM was performed. The optimal cutoff value of pretreatment systemic immune-inflammation index (SII) was determined by receiver operating characteristic curve. Kaplan-Meier curves and Cox regression analysis were performed to assess the potential prognostic roles of parameters. Results: A total of 59.8% (n=58) patients are male, with a median age of 56.0 years (range 18-77). The optimal cutoff value of SII was 988.6×109/L. High and low SII were found in 44 (45.4%) and 53 (54.6%) patients, respectively. Median survival time for total 97 cases was 18.5 months. The median overall survival for patients with low and high SII was 47.0 and 13.0 months, respectively. The 1-, 2- and 3-year survival rates for patients with low SII were 85.8%, 57.8% and 52.0% compared to that of 53.9%, 23.6% and 13.8% in patients with high SII. On univariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS)<2 points, low SII and adjuvant treatment (P<0.05) were found to be closely correlated with a better prognosis of MPM. Only ECOG PS (P=0.036) and SII (P=0.009) held statistical significance on multivariate analysis. Conclusion: Pretreatment SII is easy to access to, and it represents an efficiency and noninvasive biomarker of MPM. High SII represents an unfavorable independent prognostic factor of MPM, and this needs to be validated in further studies.

Magnetoencephalographic Imaging of Auditory and Somatosensory Cortical Responses in Children with Autism and Sensory Processing Dysfunction.

This study compared magnetoencephalographic (MEG) imaging-derived indices of auditory and somatosensory cortical processing in children aged 8-12 years with autism spectrum disorder (ASD; N = 18), those with sensory processing dysfunction (SPD; N = 13) who do not meet ASD criteria, and typically developing control (TDC; N = 19) participants. The magnitude of responses to both auditory and tactile stimulation was comparable across all three groups; however, the M200 latency response from the left auditory cortex was significantly delayed in the ASD group relative to both the TDC and SPD groups, whereas the somatosensory response of the ASD group was only delayed relative to TDC participants. The SPD group did not significantly differ from either group in terms of somatosensory latency, suggesting that participants with SPD may have an intermediate phenotype between ASD and TDC with regard to somatosensory processing. For the ASD group, correlation analyses indicated that the left M200 latency delay was significantly associated with performance on the WISC-IV Verbal Comprehension Index as well as the DSTP Acoustic-Linguistic index. Further, these cortical auditory response delays were not associated with somatosensory cortical response delays or cognitive processing speed in the ASD group, suggesting that auditory delays in ASD are domain specific rather than associated with generalized processing delays. The specificity of these auditory delays to the ASD group, in addition to their correlation with verbal abilities, suggests that auditory sensory dysfunction may be implicated in communication symptoms in ASD, motivating further research aimed at understanding the impact of sensory dysfunction on the developing brain.

Over-Expression of TBL1XR1 Indicates Poor Prognosis of Serous Epithelial Ovarian Cancer.

Transducin (ß)-like 1 X-linked receptor 1 (TBL1XR1) is a core component of the NCoR/SMRT transcription co-repressor complex, and its role in regulating cancer progression has been reported. Serous epithelial ovarian cancer (EOC) is the most common histological type of EOC. Here we explored the significance of TBL1XR1 expression in predicting outcomes of patients with serous EOC. Real-time quantitative PCR analysis showed that the expression level of TBL1XR1 mRNA was significantly higher in EOC tissues compared with adjacent non-tumorous tissues. The protein levels of TBL1XR1 in EOC tissues were assessed by immunohistochemistry, and the patients were classified into low-expression group (n = 62) and high-expression group (n = 54) according to the immunoreactivity. Prognostic significance of TBL1XR1 was evaluated by univariate and multivariate analyses, showing that over-expression of TBL1XR1 was correlated with poor prognosis. In addition, TBL1XR1 was positively associated with the lymph node metastasis of EOC. Because vascular endothelial growth factor (VEGF)-C is known as a critical mediator of lymph node metastasis, we measured the expression level of VEGF-C mRNA in EOC tissues and thus identified a positive correlation between TBL1XR1 and VEGF-C mRNA levels. Subsequently, using human EOC cell lines, we showed that silencing of TBL1XR1 decreased VEGF-C expression, suggesting that TBL1XR1 may function as an upstream regulator of VEGF-C in EOC. Furthermore, the proliferation and invasion of EOC cells were inhibited by TBL1XR1 silencing. In conclusion, TBL1XR1 overexpression may be an unfavorable prognostic factor for EOC. We also suggest that the TBL1XR1-VEGF-C axis may determine the EOC progression.

Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells.

Nitidine chloride (NC) exhibits anti-tumor properties in various types of tumor. However, to the best of our knowledge there is no previous evidence of NC involvement in the apoptosis or proliferation of ovarian cancer cells and the underlying molecular mechanisms. The present study aimed to investigate the influence of NC on the viability and apoptosis of ovarian cancer cells and the synergistic effect NC and doxorubicin (DOX) may have on ovarian cancer cells. The viability and proliferation of ovarian cancer cells were examined using a methyl thiazolyl tetrazolium assay and 3H-thymidine incorporation assay. The apoptotic rate of ovarian cancer cells was detected by flow cytometry. The expression of apoptosis­associated proteins and Akt serine/threonine kinase 1 (Akt) were determined by western blot analysis following NC treatment. The inhibitory effect of NC on the proliferation of ovarian cancer cells was demonstrated in a time and dose­dependent manner. The pro-apoptotic effect of NC on ovarian cancer cells was also observed. It was determined that NC significantly downregulated the protein expression levels of B­cell CLL/lymphoma 2 (Bcl-2) and upregulated the expression of Bcl­2­associated X protein, p53, caspase­3 and ­9. NC suppressed Akt phosphorylation. Additionally, the present study demonstrated that the effect of NC on the proliferation and apoptosis of ovarian cancer cells was Akt­dependent by using the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt signaling pathway inhibitor, LY294002. NC exhibited a synergistic inhibitory effect on the viability of ovarian cancer cells when combined with DOX. The current study demonstrated that NC inhibited the proliferation and induced the apoptosis of ovarian cancer cells via the Akt signaling pathway and highlighted its potential clinical application for the treatment of ovarian cancer.

Ubiquitin-specific protease 7 expression is a prognostic factor in epithelial ovarian cancer and correlates with lymph node metastasis.

OBJECTIVE: Ubiquitin-specific protease 7 (USP7) is a common target of herpesviruses and is important in the DNA damage response, which is also upregulated in several cancers, including prostate, colon, liver, and lung cancers. However, less is known about its expression in ovarian cancer tissues. The role of USP7 in epithelial ovarian cancer (EOC) has not yet been investigated. MATERIALS AND METHODS: We recruited 141 patients from Linyi People's Hospital between June 1999 and June 2013, all pathologically diagnosed with primary EOC. Their clinical data were collected, and the expression of USP7 in the tumor tissues was determined using immunohistochemistry. The correlations between USP7 expression and the clinicopathological variables of patients with EOC were assessed using Spearman's rank correlation test. Kaplan-Meier analysis and Cox regression analysis were used to identify the prognosis value of USP7. The function of USP7 in the EOC cells was also detected in vitro. RESULTS: Among the 141 cases, USP7 expression was high in 59 EOC samples (41.8%), and was significantly correlated with lymphatic invasion; USP7 can act as independent prognostic indicator for the overall survival (OS) of EOC, and its high expression was associated with poor OS rate. The RNA inteference and overexpression assays indicated that USP7 can positively regulate the ovarian cell vitality and invasion process. CONCLUSION: Patients with EOC expressing high level of USP7 have worse OS compared with those with low USP7 expression. USP7 may be involved in the proliferation and invasion of EOC cells, and USP7 expression can serve as an independent predictor of EOC.

Verifying the markers of ovarian cancer using RNA-seq data.

Markers associated with diagnosis, presentation and potential therapeutic targets have received widespread attention in ovarian cancer research in the past few years. However, the majority of these markers have been investigated individually, and the changes in expression and the association between them are rarely documented. Next­generation sequencing, also termed RNA-seq when the sequencing targets are cDNAs, can provide a whole blueprint of the transcriptome of a specific tissue. In the present study, RNA-seq data of human ovarian cancer samples were used to verify the expression of known markers and to identify the association between them. A total of 563 markers associated with ovarian cancer were retrieved from the database of the National Center of Biotechnology Information, and used as the target markers. The transcriptome of the ovarian tissue of four different tumors, containing tumor presentation and recurrence stages, were sequenced using the Illumina GAII platform. Approximately 85.97% markers were expressed of the total 563 markers, and the majority of them were involved in pathways associated with cancer, signaling and infection. In total, 85 markers were found to be aberrantly expressed in tumor cells from patients with ovarian cancer who had recurrences, including 33 upregulated markers at the recurrence stage. Therefore, they may have roles ovarian tumor due to their aberrant expression. Differentially expressed markers and the associations between them can be assessed by examining the RNA-seq data. These findings may provide novel information for further studies on ovarian cancer.

Ampelopsin reduces the migration and invasion of ovarian cancer cells via inhibition of epithelial-to-mesenchymal transition.

Ampelopsin has displayed anticancer activity in several types of cancers. However, no evidence has been reported for the direct effect of ampelopsin on ovarian cancer cell migration and invasion, and the underling mechanisms have not yet been clearly established. The aim of the present study was to investigate the influence of ampelopsin on the migration and invasion of ovarian cancer. Proliferation and viability of the ovarian cancer cells were detected by MTT assay. Migration and invasion of the cells were detected, respectively, by scratch wound healing assay and Transwell assay. The expression levels of epithelial-to-mesenchymal transition (EMT) markers were detected at the protein level after stimulation with ampelopsin. Then, the expression levels of NF-κB and p-IκBα were detected with western blot analysis. Meanwhile, an inhibitor of NF-κB was used to investigate the effect of ampelopsin. Finally, the expression of Snail was also detected. Proliferation, migration and invasion of the A2780 cells were all inhibited following the application of ampelopsin. Ampelopsin upregulated E-cadherin and downregulated N-cadherin and vimentin in a concentration- and time-dependent manner. Ampelopsin also exerted its ability to suppress the nuclear translocation of the NF-κB pathway. Administration of the inhibitor BAY11-7082 confirmed the roles of NF-κB in the expression of EMT markers and its transcription factor. These results demonstrated that ampelopsin inhibited EMT and reduced the invasion of ovarian cancer cells via the NF-κB/Snail pathway.

"Blooming too soon": A case of precocious puberty / Philippine Journal of Obstetrics and Gynecology

Precocious puberty is the onset of pubertal development at an earlier age than is expected based upon established normal standards. The cause of precocious puberty may range from a variant of normal development (eg. premature adrenarche or isolated premature thelarche) to pathologic conditions with significant risk of morbidity and even death (eg. malignant germ-cell tumor or astrocytoma). A case of an 18 month old female presenting with vaginal bleeding following a previously noted breast enlargement was described. Initial assessment based on the patient's history and physical examination is suggestive of precocious puberty. Hormonal studies indicated normal levels of FSH and LH, with an elevation in estradiol. Radiographic analysis showed a normal bone age. Cranial MRI revealed no abnormal masses. Sonographic evaluation showed bilateral cystic masses in the ovaries. A diagnosis of peripheral precocious puberty associated with functional ovarian cysts was made, and the patient was monitored for progression of pubertal development.