A Blended Vitamin Supplement Improves Spatial Cognitive and Short-Term Memory in Aged Mice.

Although many types of antioxidant supplements are available, the effect is greater if multiple types are taken simultaneously rather than one type. However, it is difficult to know which type and how much to take, as it is possible to take too many of some vitamins. As it is difficult for general consumers to make this choice, it is important to provide information based on scientific evidence. This study investigated the various effects of continuous administration of a blended supplement to aging mice. In 18-month-old C57BL/6 mice given a blended supplement ad libitum for 1 month, spatial cognition and short-term memory in the Morris water maze and Y-maze improved compared with the normal aged mice (spontaneous alternative ratio, normal aged mice, 49.5%, supplement-treated mice, 68.67%, p < 0.01). No significant differences in brain levels of secreted neurotrophic factors, such as nerve growth factor and brain-derived neurotrophic factor, were observed between these two groups. In treadmill durability tests before and after administration, the rate of increase in running distance after administration was significantly higher than that of the untreated group (increase rate, normal aged mice, 91.17%, supplement-treated aged mice, 111.4%, p < 0.04). However, training had no reinforcing effect, and post-mortem serum tests showed a significant decrease in aspartate aminotransferase, alanine aminotransferase, and total cholesterol values. These results suggest continuous intake of a blended supplement may improve cognitive function and suppress age-related muscle decline.

A mixed antioxidant supplement improves cognitive function, and coordination in aged mice.

Accumulation of oxidative damage increases the risk of several disorders. To prevent these diseases, people consume supplements. However, there is little evidence of the impact of supplement intake on cognitive function. Recently, frailty and sarcopenia have become serious issues, and these phenomena include a risk of mild cognitive impairment. In this study, aged mice were fed the combination supplement and cognitive and motor functions were measured. Following 1 month of treatment with the supplement, significant improvements in cognitive function and neuromuscular coordination were observed. Following 2 weeks of treadmill training, treatment with the supplement dramatically increased running distance compared to that in untreated normal aged mice. Serum indices such as triglyceride and total cholesterol were significantly decreased in the supplement-treated aged mice compared to untreated aged mice. These results indicate that the combination supplement may play a role in maintaining cognitive function, coordination ability and improving lipid metabolism.

Endoscopic endonasal transmaxillary-pterygoid approach for skull-base non-vestibular schwannomas in 10 consecutive patients.

PURPOSE: Non-vestibular schwannomas (NVSs) of the skull base occur in several sites, and few previous studies have evaluated the usefulness of the endoscopic endonasal transmaxillary-pterygoid approach (EETMPA) to resect these lesions. We aimed to evaluate the characteristics and clinical outcomes of patients who underwent EETMPA for skull-base NVSs and to investigate the efficacy, safety, and indications for the procedure. METHODS: We retrospectively reviewed the clinical data of 10 consecutive patients (mean age, 45 ± 17) who underwent EETMPA for skull-base NVSs at the University of Tsukuba hospital between 2013 and 2020. We also calculated the total tumor volume and the size of the corridor to the tumor for EEA (SCEEA) in nine patients who underwent EEA for NVSs adjacent to the Meckel's cave or cavernous sinus. RESULTS: Nine patients (9/10), including five women (5/10), underwent primary surgery. Gross total resection and subtotal resection were achieved in five patients each (5/10). Postoperatively, one patient showed a new and mild cranial nerve V sensory deficit and one patient showed slight worsening of abducens nerve palsy. The greater palatine nerve was amputated in two patients; however, permanent perception loss in the soft palate was observed in one patient. The Vidian nerve was sacrificed in four patients, and new dry eye occurred in one patient. None of the patients experienced postoperative tumor recurrence or regrowth during the follow-up period of 40 ± 28 months. CONCLUSION: EETMPA is safe and effective for excising skull-base NVSs which are not eligible for radiosurgery leading to a high rate of successful resection and a high rate of but mild neurological sequela. The EEA is appropriate when the tumor extends to the paranasal sinus with sufficient SCEEA.

The transsylvian corridor through minimally invasive transcranial approaches: a comparative anatomical study.

Minimally invasive transcranial approaches (MITAs) continue to expand in popularity in neurosurgery. Only few MITAs allow sufficient sylvian exposure to enable wide use of the transsylvian corridor. In this study, we aim to compare the transsylvian corridor in two MITAs: the minipterional (MPTa) and the extended supraorbital eyebrow approaches (XSEa). Eight cadaver heads were used to quantify the surgical exposure and maneuverability along the sylvian fissure and the insular lobe provided by the MPTa and the XSEa. Surgical exposure was calculated by means of the exposed length of the sylvian fissure and by the area framed within three extreme points in the insular lobe. Maneuverability was assessed by means of the surgical freedom along the sylvian cistern. XSEa provides twice the frontal exposure and half of the temporal exposure in comparison to the MPTa (p < 0.001 and p = 0.02, respectively). No significant differences were found between the two craniotomies in the length of the exposure of the sylvian fissure, area of insular exposure, or surgical freedom. Both the MPTa and the XSEa afford sufficient grades of exposure along the sylvian fissure and the insular lobe, although the viewing angle is significantly different between the two approaches. Such properties allow either to be used for microsurgery deep within the sylvian cistern. The use of additional corridors, such as the subfrontal route (XSEa) and pretemporal route (MPTa), may influence selection of either the minipterional or the extended supraorbital approaches according to the origin of the surgical pathology addressed.

Human parechovirus-3 infection in nine neonates and infants presenting symptoms of hemophagocytic lymphohistiocytosis.

Human parechovirus-3 (HPeV-3) has been reported to cause a sepsis-like illness in neonates and young infants. We experienced the occurrence of HPeV-3 infection in nine neonates and young infants (eight boys, one girl; aged 14-52 days, median 31 days). They were admitted to our hospital with the chief complaints of fever persisting for 3-5 days (median 4 days) and lethargy. Five infants presented with abdominal distension and six had a rash (including acral reddening), as was previously reported with this viral infection. Abdominal distension with navel protrusion and acral reddening during the course were characteristic. Laboratory data were characterized by elevated values for serum AST, LDH, FDP, D-dimer, ferritin, soluble IL-2 receptor, triglyceride, choline esterase, and urinary ß(2)-microglobulin. Two of our nine patients presented with a hemophagocytic lymphohistiocytosis (HLH)-like illness and required specific therapy. These data suggest that HPeV-3 is an important virus that can cause hypercytokinemia, which sometimes leads to HLH, and systemic inflammatory response syndrome in neonates and young infants.

Risk Factors for Postoperative Cerebrospinal Fluid Leak after Graded Multilayer Cranial Base Repair with Suturing via the Endoscopic Endonasal Approach.

This study analyzed risk factors for postoperative cerebrospinal fluid (CSF) leak after graded multilayer cranial base repair method with dural suturing. We performed surgery via the endoscopic endonasal approach (EEA) from 2012.6 to 2018.4, and those consecutive clinical data were prospectively accumulated and retrospectively analyzed. We tailored the repair method according to the intraoperative CSF leak grade. Among 388 surgeries via the EEA, there were 10 (2.6%) cases of postoperative CSF leak after graded repair with suturing. Postoperative CSF leak occurred in two of the 150 cases without intraoperative CSF leak (grade 0), one of the 104 cases with small (grade 1) intraoperative CSF leak, two of the 60 cases with moderate (grade 2) leak, and five of the 74 cases with large (grade 3) leak. Univariate analysis indicated that chordoma (P = 0.023), estimated tumor volume ≥ 7400 mm3 (P = 0.003), and maximum tumor diameter ≥ 32.5 mm (P = 0.001) were significant risk factors for postoperative CSF leak. Additionally, among cases with intraoperative grade 3 CSF leak, chordoma (P = 0.021), estimated tumor volume ≥ 23000 mm3 (P = 0.003), and maximum tumor diameter ≥ 45.5 mm (P = 0.001) were significant risk factors for postoperative CSF leak. Maximum tumor diameter, estimated tumor volume, and chordoma tumor pathology are related to a higher risk of postoperative CSF leak.

HIV-1-encoded antisense RNA suppresses viral replication for a prolonged period.

BACKGROUND: Recent evidence proposes a novel concept that mammalian natural antisense RNAs play important roles in cellular homeostasis by regulating the expression of several genes. Identification and characterization of retroviral antisense RNA would provide new insights into mechanisms of replication and pathogenesis. HIV-1 encoded-antisense RNAs have been reported, although their structures and functions remain to be studied. We have tried to identify and characterize antisense RNAs of HIV-1 and their function in viral infection. RESULTS: Characterization of transcripts of HEK293T cells that were transiently transfected with an expression plasmid with HIV-1NL4-3 DNA in the antisense orientation showed that various antisense transcripts can be expressed. By screening and characterizing antisense RNAs in HIV-1NL4-3-infected cells, we defined the primary structure of a major form of HIV-1 antisense RNAs, which corresponds to a variant of previously reported ASP mRNA. This 2.6 kb RNA was transcribed from the U3 region of the 3' LTR and terminated at the env region in acutely or chronically infected cell lines and acutely infected human peripheral blood mononuclear cells. Reporter assays clearly demonstrated that the HIV-1 LTR harbours promoter activity in the reverse orientation. Mutation analyses suggested the involvement of NF-κΒ binding sites in the regulation of antisense transcription. The antisense RNA was localized in the nuclei of the infected cells. The expression of this antisense RNA suppressed HIV-1 replication for more than one month. Furthermore, the specific knockdown of this antisense RNA enhanced HIV-1 gene expression and replication. CONCLUSIONS: The results of the present study identified an accurate structure of the major form of antisense RNAs expressed from the HIV-1NL4-3 provirus and demonstrated its nuclear localization. Functional studies collectively demonstrated a new role of the antisense RNA in viral replication. Thus, we suggest a novel viral mechanism that self-limits HIV-1 replication and provides new insight into the viral life cycle.

Tuberculous meningitis with good outcome following appropriate timing of ventriculoperitoneal shunting for hydrocephalus.

BACKGROUND: Tuberculous meningitis is often associated with hydrocephalus. However, the appropriate timing for shunt placement to treat hydrocephalus remains controversial. CASE PRESENTATION: A 43-year-old man presented with high fever and disturbance of consciousness. Cerebrospinal fluid (CSF) findings showed pleocytosis, increased protein levels, and hypoglycemia with an elevated pressure of 30 cm H2O. Brain magnetic resonance imaging revealed cerebral infarctions and hydrocephalus resulting in suspicion of tuberculous meningitis. A few days after admission, external ventricular drainage was carried out for acute hydrocephalus. Four antitubercular drugs (isoniazid, rifampicin, pyrazinamide, and ethambutol) as well as dexamethasone sodium phosphate were given. The CSF polymerase chain reaction test for tuberculosis was found to be positive 2 weeks later. Once CSF protein levels improved, a ventriculoperitoneal shunting operation was undertaken. CONCLUSIONS: When tuberculous meningitis is suspected, treatment with antitubercular drugs should be initiated prior to definitive diagnosis, and a shunt surgery should be carried out in a timely manner.

Intraosseous schwannoma in the clivus mimicking chordoma treated with endoscopic endonasal surgery: A case report.

Background: Intraosseous schwannomas are extremely rare and they have not yet been reported to occur in the clivus. We report a schwannoma in the clivus mimicking chordoma and review intraosseous schwannomas of the skull. Case Description: A 62-year-old man presented with gradually worsening hoarseness with dysphagia and atrophy of the left tongue, trapezius muscle, and sternocleidomastoid muscle. Magnetic resonance imaging showed that the tumor was mainly located in the clivus, and a computed tomography (CT) scan revealed an osteolytic lesion with expansion of the clivus and preservation of the bony cortex. Endoscopic endonasal surgery was performed to diagnose and treat symptoms. The tumor was subtotally removed without any complications. The histopathological findings revealed typical schwannoma, which showed Antoni A and Antoni B patterns positive for S100 protein. Based on the preoperative imaging, intraoperative and histopathological findings, the tumor was considered to be an intraosseous schwannoma in the clivus, and no recurrence was observed after 1 year of postoperative follow-up. Conclusion: Even though the intraosseous schwannoma in the clivus is uncommon, it should be considered as a differential diagnosis if an expansive lesion without destruction of the cortical bone is shown on CT as well as iso-hyperintensity on T2-weighted magnetic resonance imaging.

Morphometric comparison of Fisch type A and endoscopic endonasal far-medial supracondylar approaches to the jugular foramen.

OBJECTIVE: The jugular foramen (JF) is one of the most complex and challenging skull base regions to approach surgically. The extreme medial approach to access the JF provides the approach angle from an anterior direction and does not require dissection and sacrifice of the jugular bulb (JB) to reach the pars nervosa. The authors compared the Fisch type A approach to the extreme medial approach to access the JF and evaluated the usefulness of the extreme medial approach. METHODS: This study was performed at the Anatomical Laboratory for Visuospatial Innovations in Otolaryngology and Neurosurgery of The Ohio State University. For the comparison of surgical maneuverability and visualization, two angles were measured: 1) the angle of attack (AoA), defined as the widest angle of movement achieved with a straight dissector; and 2) the angle of endoscopic exposure (AoEE), defined as the widest angle of movement in the nasal cavity. The differences in eustachian tube (ET) management, approach angle, surgical maneuverability, and surgical application of the Fisch type A approach to the extreme medial approach were compared. RESULTS: There was no difference between ET mobilization and transection regarding cranial-caudal (CC) or medial-lateral (ML) AoA (p = 0.646). The CC-AoA of the Fisch type A approach was significantly wider than the CC-AoA of the extreme medial approach (p = 0.001), and the CC-AoEE was significantly wider than the CC-AoA of the extreme medial approach (p < 0.001). There was no significant difference between the CC-AoA of the Fisch type A approach and the CC-AoEE. The ML-AoA of the Fisch type A approach was significantly wider than the ML-AoA of the extreme medial approach (p = 0.033), and the ML-AoEE was significantly wider than ML-AoA in the extreme medial approach (p < 0.001). The ML-AoEE was significantly wider than the ML-AoA in the Fisch type A approach (p = 0.033). CONCLUSIONS: The surgical maneuverability of the extreme medial approach was not inferior to that of the Fisch type A approach. The extreme medial approach can provide excellent surgical field visualization, while preserving the JB. Select cases of chordomas, chondrosarcomas, and JF schwannomas should be considered for an extreme medial approach. These two approaches are complementary, and a case-by-case detailed analysis should be conducted to decide the best approach.

Inducing substances for chondrogenic differentiation of dental pulp stem cells in the conditioned medium of a novel chordoma cell line.

We successfully established a chordoma cell line, designated TSK-CHO1, derived from the clival chordoma. Currently, there is only one skull base chordoma cell line, UM-chor1, freely available to researchers. The established TSK-CHO1 cells were neoplastic, exhibited pleomorphic features, and secreted brachyury, as revealed by immunocytochemical staining or ELISA of conditioned medium (CM). Cells also secreted SOX9, which enhanced brachyury production. The CM of TSK-CHO1 cells promoted the production of hyaluronic acid and type II collagen during differentiation of human dental pulp stem cells (DPSCs) into fibrocartilage cells. Culture of DPSC pellets in a growth medium supplemented with 10% CM of TSK-CHO1 cells for 2 weeks resulted in the induction of fibrocartilage tissue under normoxic conditions. Brachyury produced by TSK-CHO1 cells promoted the production of collagen type II, peculiar to cartilage, in a dose-dependent manner. The newly established skull base chordoma cell line, TSK-CHO1, is expected to be used for elucidating the pathogenesis of skull base chordoma and for investigating the mechanism underlying the production of fibrocartilage.

Perioperative Deep Vein Thrombosis and D-dimer Measurement in Patients with Brain Tumor.

We investigated the appropriate D-dimer cutoff value for each brain tumor type for acute or subacute deep vein thrombosis (DVT) following transcranial brain tumor surgery.In this single-center retrospective study, a cumulative total of 128 patients who underwent transcranial brain tumor surgery were enrolled and classified into the glioma group, the other intracranial malignant tumor group, and the intracranial benign tumor group. Venous ultrasonography was performed if the D-dimer plasma levels were positive (≥1 µg/mL) before surgery and on postoperative day (POD) 3 or 7.Of the 128 cases, DVT developed in 32 (25.0%). Among those, acute or subacute DVT was diagnosed in 22 cases on POD 3 and in 8 cases on POD 7. Compared with DVT-negative cases on POD 3, acute or subacute DVT-positive cases on POD 3 revealed a significant increase in the D-dimer level in all groups combined and in the benign tumor group but not in the glioma group. With regard to DVT on POD 3 in all groups, the receiver operating characteristic curve for the D-dimer level on POD 3 demonstrated a cutoff value of 3.3 µg/mL (sensitivity [0.636] and specificity [0.750]). However, if this cutoff value was used in practice, eight cases would be false-negative with a minimum D-dimer level of 1.5 µg/mL.The D-dimer cutoff value for acute or subacute DVT on POD 3 could be set to 3.3 µg/mL; however, the setting resulted in several false-negative cases. Practically, 1.5 µg/mL of the D-dimer cutoff value on POD 3 might be appropriate to avoid false-negative results.

Association of HLA-A*02:06 and HLA-DRB1*04:05 with clinical subtypes of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the genetic background of JIA may also be heterogeneous. The aim of this study was to investigate associations between human leukocyte antigen (HLA) and susceptibility to JIA and/or uveitis, which is one of the most devastating complications of JIA. A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1 by PCR-sequence-specific oligonucleotide probe methodology. HLA-A(*)02:06 was the risk factor for JIA accompanied by uveitis after adjustment for clinical factors (corrected P-value < 0.001, odds ratio (OR) 11.7, 95% confidence interval (CI) 3.2-43.0). On the other hand, HLA-DRB1(*)04:05 was associated with polyarticular JIA (corrected P-value < 0.001, OR 2.9, 95% CI 1.7-4.8). We found an association of HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, which might be considered a separate clinical JIA entity. We also found an association between HLA-DRB1(*)04:05 and polyarticular JIA. Thus, clinical subtypes of JIA can be classified by the presence of the specific HLA alleles, HLA-A(*)02:06 and DRB1(*)04:05.

Influence of polymorphisms within the methotrexate pathway genes on the toxicity and efficacy of methotrexate in patients with juvenile idiopathic arthritis.

AIMS: We investigated whether several polymorphisms within the methotrexate (MTX) pathway genes were related to the toxicity and efficacy of MTX in 92 Japanese patients with articular-type juvenile idiopathic arthritis (JIA). METHODS: Eight gene polymorphisms within the MTX pathway genes, namely, RFC, BCRP, MTHFR (two), FPGS, γ-glutamyl hydrolase (GGH; two) and ATIC, were genotyped using TaqMan assays. Liver dysfunction was defined as an increase in alanine transaminase to five times the normal upper limit. Non-responders to MTX were defined as patients refractory to MTX and were therefore treated with biologics. RESULTS: The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction (P=0.028, odds ratio=6.90, 95% confidence interval 1.38-34.5), even after adjustment for the duration of MTX treatment. A longer interval from disease onset to treatment (8.5 and 21.3 months, P=0.029) and rheumatoid factor positivity (P=0.026, odds ratio=2.87, 95% confidence interval 1.11-7.39) were associated with lower efficacy of MTX. CONCLUSIONS: The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction, presumably because the C allele of GGH C16T may reduce the activity of GGH. The time interval before MTX treatment and rheumatoid factor positivity were associated with the efficacy of MTX treatment. The pharmacogenetics of the MTX pathway genes affects the toxicity and efficacy of MTX in Japanese JIA patients.

Suction mask device: a simple, inexpensive, and effective method of reducing spread of aerosolized particles during endoscopic endonasal surgery in the era of COVID-19.

OBJECTIVE: Aerosol-generating procedures, including endoscopic endonasal surgery (EES), are a major risk for physicians during the COVID-19 pandemic. Techniques for reducing aerosolization and risk of transmission of COVID-19 during these procedures would be valuable to the neurosurgical community. The authors aimed to simulate the generation of small-particle aerosols during EES and craniectomy in order to develop methods to reduce the spread of aerosolized particles, and to test the effectiveness of these methods. METHODS: This study was performed at the Anatomical Laboratory for Visuospatial Innovations in Otolaryngology and Neurosurgery at The Ohio State University. The following two scenarios were used to measure three different particle sizes (0.3, 2.5, and 10 µm) generated: 1) drilling frontotemporal bone, simulating a craniectomy; and 2) drilling sphenoid bone, simulating an endonasal approach. A suction mask device was created with the aim of reducing particle release. The presence of particles was measured without suction, with a single Frazier tip suction in the field, and with the suction mask device in addition to the Frazier suction tip. Particles were measured 12 cm from the craniectomy or endonasal drilling region. RESULTS: In the absence of any aerosol-reducing devices, the number of particles measured during craniectomy was significantly higher than that generated by endonasal drilling. This was true regardless of the particle size measured (0.3 µm, p < 0.001; 2.5 µm, p < 0.001; and 10 µm, p < 0.001). The suction mask device reduced the release of particles of all sizes measured in the craniectomy simulation (0.3 µm, p < 0.001; 2.5 µm, p < 0.001; and 10 µm, p < 0.001) and particles of 0.3 µm and 2.5 µm in the single Frazier suction simulation (0.3 µm, p = 0.031; and 2.5 µm, p = 0.026). The suction mask device further reduced the release of particles of all sizes during EES simulation (0.3 µm, p < 0.001; and 2.5 µm, p < 0.001) and particles of 0.3 µm and 2.5 µm in the single Frazier suction simulation (0.3 µm, p = 0.033; and 2.5 µm, p = 0.048). Large particles (10 µm) were not detected during EES. CONCLUSIONS: The suction mask device is a simple and effective means of reducing aerosol release during EES, and it could potentially be used during mastoidectomies. This could be a valuable tool to reduce the risk of procedure-associated viral transmission during the COVID-19 pandemic.

Combined simultaneous endoscopic endonasal and microscopic transventricular surgery using a port retractor system for giant pituitary adenoma: A technical case report.

BACKGROUND: We report a case of a giant pituitary adenoma with marked extension into the third ventricle that was successfully removed using combined simultaneous endoscopic endonasal surgery (EES) and microscopic transventricular port surgery. CASE DESCRIPTION: A 47-year-old woman, who complained of memory disturbance, had a giant pituitary adenoma with marked extension into the third ventricle that was causing obstructive hydrocephalus. She underwent combined EES and microscopic transventricular surgery using a port retractor system. Most of the tumor was resected from the EES side with assistance from the transcranial side with minimum cortical trajectory damage. The tumor was completely excised without any complications. CONCLUSION: For giant pituitary adenoma with marked extension into the third ventricle, combined simultaneous EES and transventricular surgery using a port retractor system is effective to maximize the extent of tumor resection while also preventing complications. Using port surgery on the transcranial side, microscopic secure dissection is possible with minimum additional cortical damage.

Combined Endoscopic Endonasal and Bilateral Subfrontal Approach for a Nonfunctioning Pituitary Adenoma Associated with an Internal Carotid Artery-Superior Hypophyseal Artery Aneurysm.

BACKGROUND: An aneurysm embedded in a pituitary adenoma is rare, and treatment for both the aneurysm and pituitary adenoma is complex and controversial. CASE DESCRIPTION: A 53-year-old woman presented with a visual field defect. Magnetic resonance imaging showed a pituitary adenoma and coexistence of an aneurysm located at the orifice of the superior hypophyseal artery (SHA) from the internal carotid artery (ICA). The aneurysm was embedded in the pituitary adenoma; therefore, obliteration of the aneurysm was needed prior to tumor removal to prevent intraoperative rupture of the aneurysm. Although endovascular coil embolization was tried first, it was not successful. A combined endoscopic endonasal approach and transcranial approach was performed for simultaneous tumor removal and aneurysm clipping. A bilateral subfrontal approach was selected for aneurysm clipping because, using this approach, the parent artery was safely controlled from the ipsilateral trajectory, whereas exposure and clipping of the aneurysm were easily done from the contralateral trajectory. Additionally, the supine head position without rotation is comfortable for endoscopic endonasal surgery. The tumor was totally removed, and the aneurysm was safely and completely obliterated with a clip. The patient's postoperative course was uneventful, and her visual disturbance improved. CONCLUSIONS: A combined endoscopic endonasal and bilateral subfrontal approach is effective for a pituitary adenoma associated with an ICA-SHA aneurysm.

Endoscopic endonasal cyst fenestration into the sphenoid sinus using the mucosa coupling method for symptomatic Rathke's cleft cyst: a novel method for maintaining cyst drainage to prevent recurrence.

OBJECTIVE: Rathke's cleft cyst (RCC) is a benign cystic lesion with a relatively high incidence of local recurrence that occasionally requires repeat surgery. To prevent recurrence, simple cyst fenestration and drainage of the cyst contents to the sphenoid sinus is recommended, but it occasionally recurs. The authors postulated that obstruction of fenestration is a main cause of recurrence, and they developed a method, named the "mucosa coupling method (MC method)," that maintains persistent drainage. In this method, the RCC epithelium and the mucosa of the sphenoid sinus are connected, which promotes re-epithelialization between the two epithelia, maintaining persistent drainage. The outcome of this method was compared with that of conventional cyst fenestration. METHODS: In a consecutive series of 40 patients with RCC, the surgical strategy was changed during the study period: from December 2009 to September 2014 (the conventional period), 24 patients were scheduled to be treated using the conventional fenestration method, whereas from September 2014 to September 2017 (the MC period), 16 patients were scheduled to be treated using the MC method. However, because of an intraoperative CSF leak, the fenestration was closed during surgery in 3 patients in the conventional period and 2 in the MC period; therefore, these 5 patients were excluded from the analysis. Twenty-one patients treated with the conventional fenestration method (conventional group) and 14 patients treated with the MC method (MC group) were analyzed. All patients regularly underwent MRI after surgery to detect reaccumulation of cyst contents. The rate of reaccumulation with and without reoperation, visual outcomes, endocrinological outcomes, and postoperative complications were compared between these two groups. RESULTS: The median follow-up period in all 35 patients was 48.0 months (range 1-96 months), 54.0 months (range 1-96 months) in the conventional group and 35.5 months (range 12-51 months) in the MC group. No reaccumulation was detected on MRI in the 14 patients in the MC group, whereas it was noted in 9 (42.9%) of 21 patients in the conventional group, and 2 of these 9 patients required repeat surgery. There were no significant differences in visual and endocrinological outcomes and complications between these two groups. CONCLUSIONS: The MC method for RCC is effective for preventing obstruction of cyst fenestration, which contributes to preventing cyst reaccumulation. Furthermore, this method is equivalent to the conventional fenestration method in terms of visual and endocrinological outcomes and the complication rate.

Effect of Adalimumab on Refractory Arthritis in Juvenile Idiopathic Inflammatory Myopathy with Anti-MDA5 Autoantibody.

A 10-year-old girl manifested persistent fever, skin rash, leg pain, fatigue, and joint pain. Based on muscle weakness, elevated muscle-derived enzymes, magnetic resonance imaging, and skin biopsy results, the diagnosis was juvenile idiopathic inflammatory myopathies (JIIM). Chest CT was normal; the anti-melanoma differentiation-associated protein-5 (anti-MDA5) autoantibody was positive. Initial manifestations subsided after prednisolone (PSL) and methotrexate treatment. After the PSL dosage was decreased, the patient presented with metacarpophalangeal (MCP) joint pain and swelling in both index fingers, synovial fluid, and signals on power Doppler ultrasound. The arthritis was refractory to cyclosporine and tacrolimus. Radiography showed progressive MCP joint space narrowing and joint erosion. Adalimumab was initiated 14 months after disease onset. There was a mildly increased matrix metalloproteinase-3 (MMP3) level, an erythrocyte sedimentation ratio (ESR), and a normal CRP level. Adalimumab resulted in decreased MCP joint pain and swelling. PSL was discontinued 10 months after adalimumab initiation; after 9 more months of adalimumab, there were no significant ultrasonography findings. MMP3 and ESR levels normalized during treatment. Radiography after 2 years of adalimumab showed further progressive MCP joint space narrowing restricting dorsiflexion. This report clarified that anti-MDA5-positive JIIM joint manifestations were due to active synovitis and that adalimumab is required for severe cases. Further experience is needed to determine the pathology, severity, and prognosis of this type of arthritis.

Clinical and biological significance of adamantinomatous craniopharyngioma with CTNNB1 mutation.

OBJECTIVE: The Wnt/ß-catenin signaling pathway is strongly implicated in the pathogenesis of adamantinomatous craniopharyngioma (adaCP). However, there is no evidence that the CTNNB1 mutation activates the target gene of Wnt/ß-catenin signaling, and it is unknown whether it affects the tumorigenesis of adaCP. To assess the effect of the CTNNB1 mutation of adaCP, the authors analyzed the correlation between the mutation and clinical, radiological, pathological, and biological findings. METHODS: Between 2003 and 2015, 42 patients (24 male and 18 female, median age 42 years) with either papillary craniopharyngioma (papCP) or adaCP underwent tumor resection at the authors' institution. BRAF V600E and CTNNB1 in papCP and adaCP samples were sequenced by next-generation sequencing and the Sanger method, and mRNA expression levels of Axin2 and BMP4 were evaluated by RT-PCR. Axin2, BMP4, ß-catenin, and BRAF expression were evaluated by immunohistochemistry. Other data were collected from clinical reports. RESULTS: The BRAF V600E mutation was detected in all 10 cases of papCP (100%). CTNNB1 exon 3 mutations were detected in 21 of 31 (68%) cases of adaCP, excluding 1 case for which there were no available sequence data. The mRNA expression level of Axin2 was significantly higher in adaCPs with a CTNNB1 mutation than in those without (p < 0.05). The immunohistochemical findings of Axin2 and BMP4 did not correlate with CTNNB1 mutation positivity. When patients who received adjuvant radiation therapy were excluded, progression-free survival was shorter in the mutation-positive group than in the mutation-negative group (log-rank test, p = 0.031). Examination of clinical characteristics and immunohistochemical findings of adaCPs showed that there was no significant correlation between CTNNB1 mutation positivity and age, sex, tumor volume, gross-total resection, optic tract edema, calcification, or T1 signal intensity of cyst fluid on MRI, ß-catenin, and MIB-1 index. CONCLUSIONS: These results raise the possibility that the CTNNB1 mutation in adaCP may be associated with disease recurrence, and genes related to the Wnt/ß-catenin signaling pathway might represent a therapeutic target.