Fatal convexity and interhemispheric acute subdural hematoma from a falx meningioma: A case report.

Background: Hemorrhagic meningiomas are rare. We report a rare case of nontraumatic convexity and interhemispheric acute subdural hematoma (ASDH) caused by a falx meningioma. Case Description: An 84-year-old woman with a history of atrial fibrillation and hypertension who was taking warfarin presented to our emergency department with a sudden disorder of consciousness. The patient had no traumatic events associated with her symptoms. Computed tomography (CT) revealed right convexity and interhemispheric ASDH, mass lesions in the left frontal lobes, and brain herniation. Contrast-enhanced CT revealed vascular structures within the mass lesion. CT angiography (CTA) revealed no aneurysm or arteriovenous malformation, and the venous phase revealed occlusion in the anterior portion of the superior sagittal sinus. The patient had her right convexity and interhemispheric ASDH removed endoscopically. A mass lesion located on the falx, which was easily bleeding, soft, and suctionable, was immediately detected. Histopathological examination revealed fibrous meningioma, a benign meningioma of the World Health Organization grade 1. Despite undergoing aggressive treatment, the patient's general condition deteriorated. Conclusion: Hemorrhagic meningiomas can easily be missed with plain CT, and the enhancement effect of CTA and tumor shadow on digital subtraction angiography may not be observed during the acute phase. Surgery for nontraumatic ASDH should be performed considering the possibility that a meningioma causes it.

Immediate Effects, Detailed Clinical Outcomes, and Prognostic Factors of Chemonucleolysis Using Condoliase for Lumbar Disc Herniation.

Chemonucleolysis utilizing condoliase is a minimally invasive treatment for lumbar disc herniation (LDH) aimed at reducing intervertebral disc pressure and enhancing symptoms. In this study, lower limb pain was measured using the numeric rating scale (NRS) the day after treatment and 1 and 3 months after treatment. Prognostic factors were assessed, categorizing participants into an improvement group (I-group) for NRS lower limb pain scores of ≥3.5 and a non-improvement group (N-group) for scores of <3.5. This study included a total of 225 patients treated between April 2020 and March 2023. The mean age was 46.5 ± 16.5 years, with 151 males. The mean duration of illness was 6.2 ± 8.52 months. As of the day after treatment, 60 cases were classified into the I-group, 118 cases at 1 month after surgery, and 152 cases at 3 months after surgery. The disease duration before treatment was significantly shorter in the I-group at 1 (8.19 ± 8.74 [I-group] vs. 5.17 ± 8.04 [N-group] months) and 3 months (8.51 [I-group] ± 7.35 vs. 5.69 ± 8.87[N-group] months) after treatment. The comparison of baseline leg pain NRS shows a difference in leg pain NRS in the I-group when compared on the day after treatment (6.02 ± 2.64 [I-group] vs. 7.50 ± 1.79 [N-group]), 1 (5.13 ± 2.69 [I-group] vs. 7.58 ± 1.66 [N-group]), and 3 months (4.42 ± 2.70 [I-group] vs. 7.34 ± 1.77 [N-group]). Chemonucleolysis using condoliase for LDH can improve symptoms the day after treatment and can be a minimally invasive treatment to avoid surgery.

Usefulness of non-slip element percutaneous transluminal angioplasty scoring balloons in treating severe calcified lesions of the carotid artery for carotid artery stenting: A case report.

Background: Treatment of calcified lesions with conventional angioplasty balloons can be difficult due to insufficient lumen expansion, high dissection rates, and repeated revascularization. We report a case in which a scoring balloon was used in lesions resistant to angioplasty with a semi-compliant balloon. Case Description: A 72-year-old man presented with severe stenosis and a highly calcified lesion in the right cervical internal carotid artery. Right carotid artery stenting (CAS) was planned to prevent future ischemic stroke events. Conventional semi-compliant balloon angioplasty was unsuccessful. Three inflations of a non-slip element (NSE) percutaneous transluminal angioplasty (PTA) scoring balloon (Nipro, Osaka, Japan) successfully achieved CAS without complications. Conclusion: This is the first report to describe the use of this scoring balloon in de novo carotid artery disease. NSE PTA scoring balloon catheters can be a useful option for refractory, highly calcified stenosis.

Clonal origin and genomic diversity in Lynch syndrome-associated endometrial cancer with multiple synchronous tumors: Identification of the pathogenicity of MLH1 p.L582H.

Lynch syndrome-associated endometrial cancer patients often present multiple synchronous tumors and this assessment can affect treatment strategies. We present a case of a 27-year-old woman with tumors in the uterine corpus, cervix, and ovaries who was diagnosed with endometrial cancer and exhibited cervical invasion and ovarian metastasis. Her family history suggested Lynch syndrome, and genetic testing identified a variant of uncertain significance, MLH1 p.L582H. We conducted immunohistochemical staining, microsatellite instability analysis, and Sanger sequencing for Lynch syndrome-associated cancers in three generations of the family and identified consistent MLH1 loss. Whole-exome sequencing for the corpus, cervical, and ovarian tumors of the proband identified a copy-neutral loss of heterozygosity (LOH) occurring at the MLH1 position in all tumors. This indicated that the germline variant and the copy-neutral LOH led to biallelic loss of MLH1 and was the cause of cancer initiation. All tumors shared a portion of somatic mutations with high mutant allele frequencies, suggesting a common clonal origin. There were no mutations shared only between the cervix and ovary samples. The profiles of mutant allele frequencies shared between the corpus and cervix or ovary indicated that two different subclones originating from the corpus independently metastasized to the cervix or ovary. Additionally, all tumors presented unique mutations in endometrial cancer-associated genes such as ARID1A and PIK3CA. In conclusion, we demonstrated clonal origin and genomic diversity in a Lynch syndrome-associated endometrial cancer, suggesting the importance of evaluating multiple sites in Lynch syndrome patients with synchronous tumors.

Subarachnoid iodine leakage on dual-energy computed tomography after mechanical thrombectomy is associated with malignant brain edema.

BACKGROUND: Dual-energy computed tomography (DE-CT) can differentiate between hemorrhage and iodine contrast medium leakage following mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We determined whether subarachnoid hemorrhage (SAH) and subarachnoid iodine leakage (SAIL) on DE-CT following MT were associated with malignant brain edema (MBE). METHODS: We analyzed the medical records of 81 consecutive anterior circulation AIS patients who underwent MT. SAH or SAIL was diagnosed via DE-CT performed immediately after MT. We compared the procedural data, infarct volumes, MBE, and modified Rankin scale 0-2 at 90 days between patients with and without SAH and between patients with and without SAIL. Furthermore, we evaluated the association between patient characteristics and MBE. RESULTS: A total of 20 (25%) patients had SAH and 51 (63%) had SAIL. No difference in diffusion-weighted imaging (DWI)-infarct volume before MT was observed between patients with and without SAH or patients with and without SAIL. However, patients with SAIL had larger DWI-infarct volumes 1 day following MT than patients without SAIL (95 mL vs 29 mL; p=0.003). MBE occurred in 12 of 81 patients (15%); more patients with SAIL had MBE than patients without SAIL (22% vs 3%; p=0.027). Severe SAIL was significantly associated with MBE (OR, 12.5; 95% CI, 1.20-131; p=0.006), whereas SAH was not associated with MBE. CONCLUSION: This study demonstrated that SAIL on DE-CT immediately after MT was associated with infarct volume expansion and MBE.

Prevalence of Double Incontinence and Lower Urinary Tract Symptoms in Patients with Fecal Incontinence: A Single-center Observational Study.

Objectives: Double incontinence (DI), which is the co-occurrence of fecal incontinence (FI) and urinary incontinence (UI), increases with age and has a greater negative impact on the quality of life (QOL) than either incontinence alone. We aimed to assess lower urinary tract symptoms (LUTS) in patients with FI to elucidate the prevalence and characteristics of DI. Methods: This study enrolled consecutive patients who visited our hospital with FI symptoms. FI was evaluated using the Cleveland Clinic Florida Fecal Incontinence Score (CCFIS). LUTS were assessed using the International Prostate Symptom Score (IPSS), QOL score (IPSS-QOL) and Overactive Bladder Symptom Score (OABSS). Results: This study evaluated 140 patients (96 women [mean age: 70.7 years] and 44 men [mean age: 74.4 years]). The mean IPSS was significantly higher in men than in women (12.0 vs. 7.5, p = 0.003). A positive correlation was found between IPSS and CCFIS in women (r = 0.256, p = 0.012) but not in men. For both sexes, the older group (aged ≥70 years) had higher OABSS scores and more urge UI instances than the younger group (aged ≤69 years). Of the 140 patients with FI, 78 (55.7%) had DI, and DI was more common in women than in men (63.5% vs. 38.6%, p = 0.006). Conclusions: The characteristics of LUTS and UI in patients with FI were comparable to those in the general population for both sexes; however, the prevalence of DI was much higher among patients with FI than that in the general population.

Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial.

Importance: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke. Objective: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset. Design, Setting, and Participants: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022. Exposure: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset. Main Outcomes and Measures: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test. Results: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups. Conclusions and Relevance: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study. Trial Registration: ClinicalTrials.gov Identifier: NCT02961504.

Three-Dimensional (3D) Microcatheter Shaping Using Touch Screen Devices for Cerebral Aneurysm Coil Embolization.

OBJECTIVE: In cerebral aneurysm coil embolization, proper microcatheter shaping is crucial to reduce complications and achieve sufficient embolization. Shaping a microcatheter in 3 dimensions (3D) is often required but can be challenging. We assessed the usefulness of a novel shaping on screen (SOS) method that displays real-size 3D rotational angiography (RA) images on a touch screen device during cerebral aneurysm embolization to facilitate 3D microcatheter shaping. METHODS: In this study, 18 patients with cerebral aneurysm treated with this technique were included. Real-size 3D-RA images obtained during the embolization procedure were displayed on the touch screen device, which allowed for real-time manipulation. The shape of the microcatheter was adjusted to conform to the curvature of the vessel by swiping the touch screen device and bending the mandrel accordingly. We assessed the clinical and angiographic results, along with the accuracy and stability of the microcatheter. RESULTS: No procedure-related complications were observed. The mean packing density was 41% ± 12%. In all but 1 case, microcatheters were inserted into the aneurysms without guidewire assistance. After coiling, all microcatheter forms were stable. CONCLUSIONS: Three-dimensional (3D) microcatheter shaping using touch screen devices during cerebral aneurysm coil embolization may be simple and safe and can achieve high packing density of aneurysms.

Hypoxia-Induced Biosynthesis of the Extracellular Matrix Molecules, Perlecan and Fibronectin, Promotes the Growth of Pleomorphic Adenoma Cells In Vitro Models.

Salivary pleomorphic adenoma is histopathologically characterized by its colorful stroma with myxoid, chondroid, and hyaline appearances, due to enhanced biosynthesis of extracellular matrix (ECM) molecules and poor vascularity. Thus, pleomorphic adenoma cells embedded in the stroma typically survive under hypoxic conditions. We determined the expression kinetics of ECM molecules, such as perlecan and fibronectin (FN), under hypoxia in SM-AP1 cells which are duct epithelial differentiated cells, and in SM-AP4 cells, which are myoepithelial differentiated cells, cloned from pleomorphic adenoma of the parotid gland. We investigated hypoxia-inducible factor-1α (HIF-1α)-inducing pathways through a variety of ECM molecules in association with their cellular proliferation and migration. We observed that hypoxic conditions with elevated HIF-1α protein levels induced increased expression of perlecan and FN in SM-AP cells than in controls. Moreover, perlecan and FN knockdown reduced the proliferation of SM-AP1 and SM-AP4 cells under hypoxia. Further, SM-AP1 cell migration was enhanced by both perlecan and FN knockdown, whereas SM-AP4 cell migration was increased by perlecan knockdown and inhibited by fibronectin knockdown. The results indicated that pleomorphic adenoma cells can survive under hypoxic conditions by promoting cell proliferation via enhanced synthesis of ECM molecules. Overall, ECM molecules may be a new anti-tumor target under hypoxic conditions.

Long-term Efficacy and Safety of Controlled Manual Anal Dilatation in the Treatment of Chronic Anal Fissures: A Single-center Observational Study.

Objectives: Conventional anal dilatation for anal fissures has long been abandoned because of the high incidence of anal incontinence. However, less invasive and more precise dilation techniques have been developed that have shown high healing and low incontinence rates. This study aimed to evaluate the efficacy and safety of controlled anal dilatation (CAD) using a standardized maximum anal diameter. Methods: This study included 523 patients who underwent CAD for chronic anal fissures between January 2010 and December 2014. CAD was performed under sacral epidural anesthesia. The index fingers of both hands were placed in the anus and dilated evenly in various directions. CAD was completed when the anus was dilated to the sixth scale (35 mm in diameter) using a caliber ruler. Results: The mean anal scale size expanded from 3.1 to 5.8 (p<0.001). Non-healing was observed in nine patients (1.7%) at 1 month postoperatively, six of whom underwent additional CAD. The mean maximal anal resting pressure (mmHg) decreased from 90.2 to 79.7 at three months postoperatively (p<0.001). Postoperative complications were observed in 11 (2.1%) patients, of whom three patients with thrombosed hemorrhoids underwent resection. None of the patients complained of anal incontinence during the mean follow-up period of 16.6 months. The cumulative recurrence-free rates at three and five years were 87.9% and 69.2%, respectively. Conclusions: CAD is technically simple and safe and can achieve reasonable long-term outcomes. Thus, CAD appears to be the preferred procedure for patients with chronic anal fissures who do not respond to conservative treatments.

Pituitary adenoma presenting as isolated oculomotor nerve palsy.

Background: Isolated oculomotor nerve palsy is a relatively uncommon symptom of pituitary adenoma that usually occurs in association with pituitary apoplexy or cavernous sinus (CS) invasion. Case Description: We report two cases of relatively small pituitary adenomas with neither apoplexy nor CS invasion presenting as isolated oculomotor nerve palsy. Both patients presented with gradually worsening diplopia, without headache or visual field defects. Magnetic resonance imaging (MRI) showed a pituitary tumor with no evidence of intratumoral hemorrhage. Computed tomography revealed a lateroposterior extension of the tumor with the erosion of the posterior clinoid process. Constructive interference in steady-state MRI revealed compression of the oculomotor nerve by the tumor at the oculomotor triangle. The patients underwent endoscopic transsphenoidal surgery, and the intraoperative findings showed that the tumors did not invade the CS. The tumors were completely resected, and the oculomotor palsies resolved fully. Conclusion: These cases illustrate the need to consider isolated oculomotor nerve palsy as an initial manifestation of a relatively small pituitary adenoma with neither apoplexy nor CS invasion. Based on the characteristic radiological findings, early surgical treatment is recommended to preserve oculomotor function.

Are There Sex Differences in Defecation Patterns in Patients with Defecation Disorders? - A Single-center Observational Study.

Objectives: Defecation disorders (DD) are characterized by impaired rectal evacuation due to inadequate defecatory propulsion and/or dyssynergic defecation. DD are assessed by rectal and anal pressures during attempted defecation using anorectal manometry (ARM). Thus far, at least four types of dyssynergic patterns have been recognized on ARM. This study aimed to compare the manometric parameters and dyssynergic patterns between men and women with DD. Methods: This study enrolled consecutive patients undergoing anorectal tests for symptoms of DD. Anorectal pressure was measured using a waveform ARM system. DD were diagnosed based on the results of ARM, balloon expulsion tests, and barium defecography. Dyssynergic patterns were defined as a paradoxical increase in anal pressure with (type I) or without (type II) an adequate increase in rectal pressure and failure of a reduction in anal pressure with (type III) or without (type IV) an adequate increase in rectal pressure. Results: This study evaluated 324 women and 234 men. Based on anorectal tests, 73.1% men and 54.6% women were diagnosed with DD. Rectal and anal pressures during attempted defecation in patients with DD were significantly higher in men than in women. Type I patterns were more common in men (64.9%) than in women (28.2%). Conversely, type II (42.9% vs. 24.0%) and IV (20.9% vs. 5.8%) patterns were observed more frequently in women than in men. Conclusions: Men were more likely to experience dyssynergic defecation whereas women were more likely to experience inadequate defecatory propulsion. However, future studies are warranted to confirm these results.

Effects of Age and Sex on the Anorectal Sensory Threshold to Electrical Stimulation: A Single-center Observational Study.

Objectives: Anorectal sensation is an essential component for maintaining normal defecation and continence. This study aimed to investigate changes in anorectal sensation with age and sex using the anorectal sensory threshold to electrical stimulation in a large population with a broad age spectrum. Methods: This study enrolled consecutive adult patients (20-89 years old) who underwent anorectal physiology tests to screen for functional or organic anorectal disease. Anorectal sensitivity was measured using an endoanal electrode with a 45-mm long bipolar needle. A constant electrical current was delivered to the lower end of the rectum and the anal canal. The minimum current in milliamperes at which the initial sensation was felt was defined as the sensory threshold. Results: Overall, 888 patients were included in this study. The most frequent comorbidities were constipation and hemorrhoids. The median sensory threshold for all patients was 0.5 (interquartile range, 0.2-1.5) mA, and the overall sensory threshold was significantly higher in men than in women. The 95% confidence interval of the sensory threshold for men and women were 0.1-6.8 and 0.1-5.1 mA, respectively. The sensory threshold increased significantly with age in both sexes (men, r = 0.384; women, r = 0.410). There was no sex difference in the sensory threshold between ages 20 and 40 years; however, between ages 50 and 70 years, men had a higher sensory threshold than women. Conclusions: The anorectal sensory threshold to electrical stimulation increased with age, and the influence of aging was more significant in men than in women.

Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma.

Cholesterol plays an important role in cancer progression, as it is utilized in membrane biogenesis and cell signaling. Cholesterol-lowering drugs have exhibited tumor-suppressive effects in oral squamous cell carcinoma (OSCC), suggesting that cholesterol is also essential in OSCC pathogenesis. However, the direct effects of cholesterol on OSCC cells remain unclear. Here, we investigated the role of cholesterol in OSCC with respect to caveolin-1 (CAV1), a cholesterol-binding protein involved in intracellular cholesterol transport. Cholesterol levels in OSCC cell lines were depleted using methyl-ß-cyclodextrin and increased using the methyl-ß-cyclodextrin-cholesterol complex. Functional analysis was performed using timelapse imaging, and CAV1 expression in cholesterol-manipulated cells was investigated using immunofluorescence and immunoblotting assays. CAV1 immunohistochemistry was performed on surgical OSCC samples. We observed that cholesterol addition induced polarized cell morphology, along with CAV1 localization at the trailing edge, and promoted cell migration. Moreover, CAV1 was upregulated in the lipid rafts and formed aggregates in the plasma membrane in cholesterol-added cells. High membranous CAV1 expression in tissue specimens was associated with OSCC recurrence. Therefore, cholesterol promotes the migration of OSCC cells by regulating cell polarity and CAV1 localization to the lipid raft. Furthermore, membranous CAV1 expression is a potential prognostic marker for OSCC patients.

Clinicopathologic analysis of pineal parenchymal tumors of intermediate differentiation: a multi-institutional cohort study by the Kyushu Neuro-Oncology Study Group.

PURPOSE: Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor. METHODS: At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort. RESULTS: PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49 years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation. CONCLUSIONS: Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.

Hypertension, cerebral Amyloid, aGe Associated Known neuroimaging markers of cerebral small vessel disease Undertaken with stroke REgistry (HAGAKURE) prospective cohort study: Baseline characteristics and association of cerebral small vessel disease with prognosis in an ischemic stroke cohort.

Introduction: Cerebral small vessel disease (SVD) is one of the leading causes of stroke; each neuroimaging marker of SVD is correlated with vascular risk factors and associated with poor prognosis after stroke. However, longitudinal studies investigating the association between comprehensive SVD burden scoring system, "total SVD score" - which encompasses the established neuroimaging markers of lacunae, cerebral microbleeds (CMBs), white matter hyperintensities (WMH) including periventricular hyperintensities, and perivascular spaces in basal ganglia- and clinical outcomes are limited. The aim of this study is to determine the association between SVD burden and long-term prognosis in patients with ischemic stroke. Methods and design: This prospective, single-center, observational study enrolled patients with acute ischemic stroke, including cerebral infarction and transient ischemic attack. Magnetic resonance imaging scans were performed, and then total SVD score (range, 0-4) was calculated. We recorded baseline characteristics and evaluated the relationships of long-term outcomes to SVD neuroimaging markers and total SVD score. Stroke recurrence was thought as primary outcome. Hazard ratios (HRs) of events during follow-up were calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and smoking. Cumulative event rates were estimated using the Kaplan-Meier method. Results: Consecutive 564 acute ischemic stroke patients were enrolled according to inclusion and exclusion criteria. A total of 467 participants with first-ever ischemic stroke were analyzed (median age 75.0 [interquartile range, 64.0-83.0] years, 59.3% male). Total SVD score was 0 point in 47 individuals (12.0%), 1 point in 83 (21.2%), 2 points in 103 (26.3%), 3 points in 85 (21.7%), and 4 points in 73 (18.7%). Twenty-eight recurrent stroke events were identified during follow-up. Total SVD score ≥ 2, presence of CMBs, and moderate-to-severe WMH were associated with increased risk of recurrent stroke events (HR 9.31, 95% confidence interval [CI] 2.33-64.23; HR 2.81, 95% CI 1.08-7.30; HR 2.90, 95% CI 1.22-6.88, respectively). Conclusion: The accumulation of SVD biomarkers as determined by total SVD score offered a reliable predictor of stroke recurrence. This study established a firm understanding of SVD prognosis in clinical settings.

Liquid-based cytology for differentiating two cases of pemphigus vulgaris from oral squamous cell carcinoma.

Pemphigus vulgaris (PV) is a rare autoimmune disease characterized by blisters on the skin and mucous membrane. Since it often appears in the oral mucosa first, it may be diagnosed by oral mucosal cytology. Although the cytologic finding is characterized by acantholytic cells, that is, Tzanck cells, it is important to distinguish PV from neoplastic lesions of the oral mucosal epithelium, including differentiation from atypical parabasal/basal cells, which appear in squamous cell carcinoma (SCC). In this study, we examined the cellular findings in two cases of PV and a case of well-differentiated SCC with loss of epithelial cell cohesion. The samples were prepared using liquid-based cytology, which showed small round-shaped and deeply stained atypical, orangeophilic keratinocytes not only in SCC but also in PV, which made differentiation between the two difficult. However, Tzanck cells found in PV differ from the deep atypical parabasal/basal cells of SCC, suggesting that the cell outline is indistinct and small protrusions and brush-like structures are observed. This feature of Tzanck cells may be useful in cytological judgment.

A multicenter, randomized, placebo-controlled phase IIb trial of an autologous formalin-fixed tumor vaccine for newly diagnosed glioblastomas.

OBJECTIVE: An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. METHODS: Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. RESULTS: Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. CONCLUSIONS: The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry).

Efficacy and safety of anal encirclement combining the Leeds-Keio artificial ligament with injection sclerotherapy using aluminum potassium sulfate and tannic acid in the management of rectal prolapse: a single-center observational study.

PURPOSE: Perineal procedures are an important surgical option for frail and high-risk patients with rectal prolapse. This study aimed to evaluate the efficacy and safety of combined therapy using injection sclerotherapy, with aluminum potassium sulfate and tannic acid (ALTA), and the Thiersch procedure, using the Leeds-Keio ligament (ALTA-Thiersch). METHODS: This study included 106 consecutive patients (mean age, 81.2 years) who underwent ALTA-Thiersch for rectal prolapse. The procedure was performed under caudal epidural anesthesia. ALTA was injected into the submucosa from the tip of the prolapsed rectum down to the dentate line, circumferentially, at 20 to 40 locations. The ligament tape was placed outside the external sphincter muscle and at an approximate depth of 2 cm into the middle anal canal. RESULTS: Of 106 patients, rectal prolapse was cured shortly after surgery in 105 patients. An additional tape was inserted in 1 patient who had persistent prolapse. Postoperative complications were observed in 27 patients (25.5%). Fecal impaction occurred in 12 patients; however, since it was temporary, no tape removal was required. Of the 12 cases in which the tape was infected or exposed, 11 required tape removal. There were 18 cases of recurrence at a mean follow-up of 22.1 months. Cumulative recurrence rates at 3 and 5 years were 21.3% and 38.6%, respectively. CONCLUSION: ALTA-Thiersch is a simple and safe procedure for rectal prolapse, having reasonable outcomes. The use of the Leeds-Keio ligament for anal encircling can help compensate for the disadvantages of the Thiersch operation.

Efficacy and Safety of Fig (Ficus carica L.) Leaf Tea in Adults with Mild Atopic Dermatitis: A Double-Blind, Randomized, Placebo-Controlled Preliminary Trial.

Atopic dermatitis (AD) is a chronic, recurrent pruritic skin disease with repeated remissions and exacerbations. Various factors, such as allergies, skin conditions and lifestyle, combine to cause AD, making it difficult to cure completely. Although AD symptoms are suppressed with medications, this is a long-term effort and burden on patients. Thus, safer drugs and alternatives are needed. We previously found that consumption of tea prepared from fig (Ficus carica L.) leaves alleviated allergy and AD symptoms in cultured cells and animals. Therefore, here, we conducted a double-blind, randomized, controlled study in patients with mild AD to evaluate the safety and AD-relieving effects of prolonged consumption of fig leaf tea. Positive effects of fig leaf tea consumption were confirmed in 14 of 15 participants. Eczema Area and Severity Index values were significantly lowered in the fig leaf tea-treated group than in the placebo-treated group. The effect weakened 4 weeks after the end of the intervention, suggesting that continued intake of fig leaf tea was effective. Further assessments confirmed the safety of fig leaf tea consumption and revealed no variations that might pose a health hazard. Therefore, we postulate that fig leaf tea is a natural and safe therapeutic option for AD.