Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Purpose: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and Methods: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. Results: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Forkhead box P3-positive (Foxp3 + )-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1–mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1–mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1–mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF–mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has affected all medical fields, including neurosurgery. Particularly, performing preoperative screening tests has become mandatory, potentially extending the time from admission to the emergency room and operating room, thus possibly affecting patients’ prognosis. This study aimed to determine the influence of COVID-19 screening time on patients’ postoperative prognosis. Methods: From September 10, 2020, to May 31, 2021, we retrospectively evaluated 54 patients with cerebral hemorrhage who underwent emergency surgery in the emergency room after the screening test. The control group included 89 patients with cerebral hemorrhage who underwent emergency surgery between January 2019 and March 2020, i.e., the period before the COVID-19 pandemic. Prognosis was measured using the Glasgow Coma Scale scores, which were obtained preoperatively, postoperatively, and at discharge, and the modified Rankin Scale (mRS). Additionally, unfavorable outcomes (mRS score 3–6) and in-hospital mortality rates were investigated for postoperative prognostic assessments. Results: No remarkable differences were observed in the time to surgical intervention and prognostic evaluation scores between patients with cerebral hemorrhage who underwent COVID-19 screening tests and subjects in the control group. Conclusion This study confirmed that patient treatment and prognosis were not significantly affected by additional preoperative screening testing times during the pandemic. We believe that our results are informative for the evaluation and performance of emergency neurosurgery during the pandemic.

The duplicated middle cerebral artery (DMCA) is an anatomic variation that arises from the distal internal carotid artery (ICA) and supplies blood to the middle cerebral artery (MCA) territory. Aneurysms of the DMCA have been reported in 36 cases in 2020. We also report a case of a 3.7 mm saccular aneurysm originating from the DMCA. A 52-year-old woman visited our hospital with worsening headache. She had no neurological abnormalities. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) revealed a right distal ICA aneurysm at the anterior choroidal artery. Cerebral angiography was performed to confirm the shape and the size of the aneurysm. Cerebral angiography revealed that the vessel that was originally identified as the anterior choroidal artery by the MRA was actually the duplicated MCA that was originating from the aneurysm neck and was supplying the MCA territory. The patient’s aneurysm was clipped using a transsylvian approach and she recovered without any neurological symptoms. DMCAs are rare and often associated with aneurysms and require preoperative evaluation to confirm the vascular status, aneurysm characteristics, and the shape of the parent artery.

The duplicated middle cerebral artery (DMCA) is an anatomic variation that arises from the distal internal carotid artery (ICA) and supplies blood to the middle cerebral artery (MCA) territory. Aneurysms of the DMCA have been reported in 36 cases in 2020. We also report a case of a 3.7 mm saccular aneurysm originating from the DMCA. A 52-year-old woman visited our hospital with worsening headache. She had no neurological abnormalities. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) revealed a right distal ICA aneurysm at the anterior choroidal artery. Cerebral angiography was performed to confirm the shape and the size of the aneurysm. Cerebral angiography revealed that the vessel that was originally identified as the anterior choroidal artery by the MRA was actually the duplicated MCA that was originating from the aneurysm neck and was supplying the MCA territory. The patient’s aneurysm was clipped using a transsylvian approach and she recovered without any neurological symptoms. DMCAs are rare and often associated with aneurysms and require preoperative evaluation to confirm the vascular status, aneurysm characteristics, and the shape of the parent artery.

Objective: : Vertebral artery dissecting aneurysm (VADA) is a very rare subtype of intracranial aneurysms; when ruptured, it is associated with significantly high rates of morbidity and mortality. Despite several discussions and debates, the optimal treatment for VADA has not yet been established. In the last 10 years, flow diverter devices (FDD) have emerged as a challenging and new treatment method, and various clinical and radiological results have been reported about their safety and effectiveness. The aim of our study was to evaluate the clinical and radiological results with the use of FDD in the treatment of unruptured VADA. Methods: : We retrospectively evaluated the data of all patients with unruptured VADA treated with FDD between January 2018 and February 2021 at our hybrid operating room. Nine patients with unruptured VADA, deemed hemodynamically unstable, were treated with FDD. Among other parameters, the technical feasibility of the procedure, procedure-related complications, angiographic results, and clinical outcomes were evaluated. Results: : Successful FDD deployment was achieved in all cases, and the immediate follow-up angiography showed intra-aneurysmal contrast stasis with parent artery preservation. A temporary episode of facial numbness and palsy was noted in one patient; however, the symptoms had completely disappeared when followed up at the outpatient clinic 2 weeks after the procedure. The 3–6 months follow-up angiography (n=9) demonstrated completeear-complete obliteration of the aneurysm in seven patients, and partial obliteration and segmental occlusion in one patient each. In the patient who achieved only partial obliteration, there was a sac 13 mm in size, and there was no change in the 1-year follow-up angiography. In the patient with segmental occlusion, the cause could not be determined. The clinical outcome was modified Rankin Scale 0 in all patients. Conclusion : Our preliminary study using FDD to treat hemodynamically unstable unruptured VADA showed that FDD is safe and effective. Our study has limitations in that the number of cases is small, and it is not a prospective study. However, we believe that the study contributes to evidence regarding the safety and effectiveness of FDD in the treatment of unruptured VADA.