Machine learning-based detection of sleep-disordered breathing in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is often concomitant with sleep-disordered breathing (SDB), which can cause adverse cardiovascular events. Although an appropriate approach to SDB prevents cardiac remodelling, detection of concomitant SDB in patients with HCM remains suboptimal. Thus, we aimed to develop a machine learning-based discriminant model for SDB in HCM. METHODS: In the present multicentre study, we consecutively registered patients with HCM and performed nocturnal oximetry. The outcome was a high Oxygen Desaturation Index (ODI), defined as 3% ODI >10, which significantly correlated with the presence of moderate or severe SDB. We randomly divided the whole participants into a training set (80%) and a test set (20%). With data from the training set, we developed a random forest discriminant model for high ODI based on clinical parameters. We tested the ability of the discriminant model on the test set and compared it with a previous logistic regression model for distinguishing SDB in patients with HCM. RESULTS: Among 369 patients with HCM, 228 (61.8%) had high ODI. In the test set, the area under the receiver operating characteristic curve of the discriminant model was 0.86 (95% CI 0.77 to 0.94). The sensitivity was 0.91 (95% CI 0.79 to 0.98) and specificity was 0.68 (95% CI 0.48 to 0.84). When the test set was divided into low-probability and high-probability groups, the high-probability group had a higher prevalence of high ODI than the low-probability group (82.4% vs 17.4%, OR 20.9 (95% CI 5.3 to 105.8), Fisher's exact test p<0.001). The discriminant model significantly outperformed the previous logistic regression model (DeLong test p=0.03). CONCLUSIONS: Our study serves as the first to develop a machine learning-based discriminant model for the concomitance of SDB in patients with HCM. The discriminant model may facilitate cost-effective screening tests and treatments for SDB in the population with HCM.

Antiproliferative effects of D-allose associated with reduced cell division frequency in glioblastoma.

Recent studies have shown that D-allose, a rare sugar, elicits antitumor effects on different types of solid cancers, such as hepatocellular carcinoma, non-small-cell lung cancer, and squamous cell carcinoma of the head and neck. In this study, we examined the effects of D-allose on the proliferation of human glioblastoma (GBM) cell lines (i.e., U251MG and U87MG) in vitro and in vivo and the underlying mechanisms. D-allose treatment inhibited the proliferation of U251MG and U87MG cells in a dose-dependent manner (3-50 mM). However, D-allose treatment did not affect cell cycles or apoptosis in these cells but significantly decreased the cell division frequency in both GBM cell lines. In a subcutaneous U87MG cell xenograft model, intraperitoneal injection of D-allose (100 mg/kg/day) significantly reduced the tumor volume in 28 days. These data indicate that D-allose-induced reduction in cell proliferation is associated with a subsequent decrease in the number of cell divisions, independent of cell-cycle arrest and apoptosis. Thus, D-allose could be an attractive additive to therapeutic strategies for GBM.

Effects of a monoclonal antibody against (pro)renin receptor on gliomagenesis.

Glioblastoma is characterized by a strong self-renewal potential and poor differentiated state. We have reported previously that the (pro)renin receptor [(P)RR] is a potential target for glioma therapy by silencing the (P)RR gene. Here, we have examined the effects of a monoclonal antibody against (P)RR on gliomagenesis. Human glioma cell lines (U251MG and U87MG) and a glioma stem cell line (MGG23) were used for the in vitro study. The expressions of the Wnt/ß-catenin signaling pathway (Wnt signaling pathway) components and stemness markers were measured by Western blotting. The effects of the (P)RR antibody on cell proliferation, sphere formation, apoptosis and migration were also examined. Subcutaneous xenografts were also examined in nude mice. Treatment with the (P)RR antibody reduced expression of Wnt signaling pathway components and stemness markers. Furthermore, the (P)RR antibody reduced cell proliferation and decreased sphere formation significantly. The treatment also suppressed migration and induced apoptosis. In a subcutaneous xenograft model, systemic administration of the (P)RR antibody reduced tumor volume significantly. These data show that treatment with the (P)RR antibody is a potential therapeutic strategy for treating glioblastoma.

Subclinical and latent cardiac dysfunction in obstructive sleep apnea and effectiveness of continuous positive airway pressure.

PURPOSE: Obstructive sleep apnea (OSA) is associated with various cardiovascular disorders. This study aimed to investigate the effects of OSA on left ventricular (LV) function in patients with OSA who were at risk for heart failure but who had not yet developed structural heart changes. The study also sought to determine the effects of continuous positive airway pressure (CPAP) in these patients. METHODS: In a retrospective study, consecutive patients with polysomnographic OSA (apnea-hypopnea index [AHI] >5) were categorized into mild (AHI < 15), moderate (15 ≤ AHI < 30), and severe OSA (AHI ≥ 30) groups. The subjects were patients with OSA and at risk for heart failure who had not yet developed structural heart changes. All study participants underwent echocardiography and two-dimensional speckle tracking analysis, and their global longitudinal strain (GLS) was calculated. RESULTS: Of 275 patients, there were 31 with mild, 92 with moderate, and 152 with severe OSA. Of patients with moderate to severe OSA (AHI ≥ 20), 206 started CPAP and 92 patients underwent follow-up echocardiogram and speckle tracking echo analysis (median period of CPAP use: 283 days [258 to 391]). GLS was significantly reduced in patients with moderate and severe OSA compared with mild OSA (-17.8±3.1 vs. -18.0±2.6 vs. -19.3±2.8%, p=0.038). The proportion of patients with GLS ≥ -18% was significantly higher among the patients with moderate to severe OSA than among those with mild OSA. GLS improved after CPAP therapy in patients with moderate to severe OSA (GLS: -18.1±2.7% to -19.0±2.8%, p=0.004). Significant improvement in GLS was confirmed, particularly among patients with good CPAP adherence. CONCLUSION: Moderate to severe OSA is associated with LV dysfunction and can be significantly improved by CPAP therapy.

Acute Myocardial Infarction Due to Coronary Artery Embolism during Chemotherapy with mFOLFOX-6 Plus Bevacizumab for Metastatic Colon Cancer.

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, may be associated with arterial embolisms. We herein report a case of acute myocardial infarction caused by coronary embolism during combination chemotherapy with mFOLFOX-6 and bevacizumab in a patient with metastatic colon cancer. Thromboembolism occurred only in the distal right posterolateral branch without stenotic lesions or plaque rupture in the proximal branch of the right coronary artery. Sole thromboaspiration was successfully performed; the final angiogram demonstrated no stenosis in the right coronary artery. Bevacizumab may be associated with acute coronary syndrome in patients with coronary risk factors, despite no significant coronary narrowing.

Emergency Transcatheter Aortic Valve Implantation in a Surgical Aortic Bioprosthetic Valve for Acute Decompensated Heart Failure Caused by Sudden Progression of Structural Valve Deterioration.

Bioprosthetic aortic valves have limited durability. We herein report sudden progression of structural valve deterioration (SVD) and a successful case of emergency transcatheter aortic valve (TAV) implantation for acute decompensated heart failure (ADHF) caused by SVD. A 79-year-old man who had undergone a Bentall operation 11 years prior was diagnosed with ADHF due to suddenly progressive SVD. Emergency TAV implantation in the surgical bioprosthetic valve was selected based on the surgical risk. Ours and previous case reports suggest that SVD can progress suddenly, even after months of stability, and that emergency TAV implantation is effective.

Difficulty Diagnosing Retrograde Type A Aortic Dissection with Intramural Hematoma and Risk of Re-dissection and Rupture: A Report of Two Cases.

Acute type A aortic dissection is a potentially fatal disease, and emergency surgery should be considered when it is diagnosed. We herein report two cases of retrograde type A aortic dissection with intramural hematoma, followed by re-dissection, rupture, and cardiac tamponade. The diagnoses in these cases had to be made carefully, as the false lumen of the ascending aorta was sometimes unclear on contrast-enhanced computed tomography.

Primary Central Nervous System Methotrexate-associated Lymphoproliferative Disorder in a Patient with Rheumatoid Arthritis: Case Report and Review of Literature.

Methotrexate (MTX) is an immunosuppressor that is widely used to treat autoimmune diseases, including rheumatoid arthritis (RA). However, it can have serious adverse effects including a lymphoma: MTX-associated lymphoproliferative disorder (MTX-LPD). Extranodal lesions are common in MTX-LPD patients. However, MTX-LPD in the central nervous system (CNS) is extremely rare with few reported cases. Here, we describe a case of primary CNS MTX-LPD in a patient with RA, with a review of the literature. A 68-year-old woman who had received MTX for her RA for more than 10 years was referred to our hospital. Head magnetic resonance imaging (MRI) showed multiple lesions with heterogeneous contrast enhancement scattered throughout both hemispheres. As immunosuppression caused by MTX was suspected, MTX was discontinued, based on a working diagnosis of MTX-LPD. We performed an open biopsy of her right temporal lesion. Histopathologic examination showed atypical CD20+ lymphoid cells, leading to a definitive diagnosis of diffuse large B-cell lymphoma (DLBCL). In situ hybridization of an Epstein-Barr virus-encoded small RNA (EBER) was positive. Sanger sequencing confirmed that both MYD88 L265 and CD79B Y196 mutations were absent. The LPD regressed after stopping MTX. Follow-up head MRI at 8 months after surgery showed no evidence of recurrence. Although primary CNS MTX-LPD is extremely rare, it should be included in the differential diagnosis when a patient receiving MTX develops CNS lesions. Diagnosis by biopsy and MTX discontinuation are required as soon as possible.

A Case of Nonconsecutive Multiple-level Lumbar Spondylolysis Successfully Treated with Single-level Repair of the Pars Interarticularis.

Lumbar spondylolysis is commonly recognized at a single-level of the lumbar spine and frequently affects the L5 pars interarticularis unilaterally or bilaterally. Some reports have described multiple-level spondylolysis, most cases of which occur at consecutive lumbar segments. We herein present a rare case of lumbar spondylolysis involving nonconsecutive multiple-level segments; only eight such cases have been reported previously. A 38-year-old man presented with a 10-month history of chronic severe low back pain. Lumbar flexion-extension radiographs and computed tomography revealed spondylolysis at the level of L3 and L5, whereas no spondylolisthesis was present and the intervertebral disc spaces were maintained at all levels. Because 6 months of conservative management failed and repeated diagnostic blocks confirmed that the fracture of the L3 pars interarticularis was generating pain, repair of the bilateral L3 pars interarticularis with the smiley face rod method was performed. At the last follow-up 1 year after surgery, the patient had resumed normal life as a laborer and reported no back pain.

Delayed Occurrence of C3 Vertebra Anterior Subluxation Diagnosed after Surgery for Epidural Hematoma.

A case of delayed occurrence of C3 vertebra anterior subluxation diagnosed 10 days after surgery for epidural hematoma is herein described. A 56-year-old man underwent surgery for right epidural hematoma. No spinal fracture was identified on the cervical-spinal computed tomography (CT) on arrival. The patient developed neck pain after the craniotomy, and cervical magnetic resonance imaging 5 days postoperatively revealed a disruption of the C3-C4 posterior ligament complex. The patient was conservatively treated with immobilization. Cervical CT 10 days postoperatively revealed C3 vertebra anterior subluxation. Posterior fixation surgery was performed 21 days after admission, and the postoperative course was uneventful. This case suggests that awareness of delayed occurrence of cervical dislocation after traumatic intracranial hemorrhage should be increased among neurosurgeons.

Repair of damaged cortical artery by direct micro-suture in surgical treatment of acute subdural hematoma: technical note.

BACKGROUND: In surgical treatment of acute subdural hematoma (ASDH), neurosurgeons frequently encounter bleeding from cortical arteries, which is usually controlled with bipolar coagulation. However, bipolar coagulation is associated with a risk of sacrificing the cortical artery, which may affect the prognosis of neurological symptoms when these cortical arteries supply critical areas. In this article, we describe microsurgical repair of damaged cortical arteries using a 10-0 nylon micro-suture in patients with arterial-origin ASDH. METHODS: After removal of the subdural hematoma, the exact bleeding point of the cortical artery was identified, and the 10-0 nylon suture stitches were placed on the arterial tear under a microscope. After completion of the micro-suture, vascular patency was confirmed by indocyanine green (ICG) videoangiography. RESULTS: From June 2015 through February 2017, microsurgical repair was performed for seven cortical arteries in six patients. All damaged arteries were located near the Sylvian fissure, and all tears were pinhole tears. The average blood flow occlusion time was 8 min (range, 0-15 min). The patency of all seven repaired arteries was successfully confirmed by ICG videoangiography. Postoperative cerebral infarction was not observed except in one patient with cerebral contusion and a history of severe head trauma. CONCLUSIONS: The present report demonstrates that repair of a cortical artery by the 10-0 nylon micro-suture is a simple and safe method with a low risk of sacrificing the artery. This technique may be a good option in the surgical treatment of arterial-origin ASDH, especially when the accompanying cerebral contusion is minimal.

A Case of Posterior Circulation Ischemic Stroke Caused by Heparin-Induced Thrombocytopenia after Detaining Hepatic Arterial Infusion Catheter.

In Japan, hepatic arterial infusion chemotherapy (HAIC) using reservoir system is recommended for patients with hepatocellular carcinoma (HCC) whose hepatic spare ability is favorable. Arterial infusion catheter is commonly detained in hepatic artery via femoral or brachial artery. In our hospital, catheter is often inserted by puncturing the left subclavian or brachial artery considering the patient's activities of daily living (ADL) during long-term detaining. However, it rarely causes posterior circulation ischemic stroke because of the left vertebral artery branches on the path of catheter. We herein report a case of posterior circulation ischemic stroke caused by heparin-induced thrombosis (HIT) after detaining hepatic arterial infusion catheter. A 63-year-old man who is under HAIC treatment for HCC was introduced to the department of neurological surgery because of vertigo and vomiting. Magnetic resonance imaging revealed sporadic fresh cerebral infarction in the bilateral cerebellar hemisphere. Carotid ultrasonography detected a floating thrombus around the part of the left vertebral subclavian artery bifurcation. Detained catheter was removed and continuous heparin administration was started immediately. However, thrombocytopenia occurred 5 days after the injection. Because 4T's score was 6 points, HIT was strongly suspected. We stopped heparin injection immediately and observed the patient's physical status strictly. After that, platelet value improved naturally. At the late date, antibodies specific for platelet factor 4/heparin complexes were positive and he was diagnosed with HIT.

The Diagnosis of Spontaneous Coronary Artery Dissection by Optical Coherence Tomography.

Spontaneous coronary artery dissection (SCAD) is rare, but it frequently presents as acute myocardial infarction. It is frequently fatal and most cases are diagnosed at autopsy. We herein present the case of a 65-year-old woman with ST-elevation and myocardial infarction due to SCAD. Optical coherence tomography (OCT) helped us to confirm the diagnosis. The information on the intravascular morphology provided by OCT imaging is much more detailed in comparison to that provided by coronary angiography (CAG) and intravascular ultrasound (IVUS).

Ischemic Tolerance of the Brain and Spinal Cord: A Review.

Ischemic tolerance is an endogenous neuroprotective phenomenon induced by sublethal ischemia. Ischemic preconditioning (IPC), the first discovered form of ischemic tolerance, is widely seen in many species and in various organs including the brain and the spinal cord. Ischemic tolerance of the spinal cord is less familiar among neurosurgeons, although it has been reported from the viewpoint of preventing ischemic spinal cord injury during aortic surgery. It is important for neurosurgeons to have opportunities to see patients with spinal cord ischemia, and to understand ischemic tolerance of the spinal cord as well as the brain. IPC has a strong neuroprotective effect in animal models of ischemia; however, clinical application of IPC for ischemic brain and spinal diseases is difficult because they cannot be predicted. In addition, one drawback of preconditioning stimuli is that they are also capable of producing injury with only minor changes to their intensity or duration. Numerous methods to induce ischemic tolerance have been discovered that vary in their timing and the site at which short-term ischemia occurs. These methods include ischemic postconditioning (IPoC), remote ischemic preconditioning (RIPC), remote ischemic perconditioning (RIPerC) and remote ischemic postconditioning (RIPoC), which has had a great impact on clinical approaches to treatment of ischemic brain and spinal cord injury. Especially RIPerC and RIPoC to induce spinal cord tolerance are considered clinically useful, however the evidence supporting these methods is currently insufficient; further experimental or clinical research in this area is thus necessary.

Loss of Fourth Electron-Transferring Tryptophan in Animal (6-4) Photolyase Impairs DNA Repair Activity in Bacterial Cells.

(6-4) photolyases [(6-4)PLs] are flavoproteins that use blue light to repair the ultraviolet-induced pyrimidine(6-4)pyrimidone photoproduct in DNA. Their flavin adenine dinucleotide (FAD) cofactor can be reduced to its repair-active FADH- form by a photoinduced electron transfer reaction. In animal (6-4)PLs, a chain of four Trp residues was suggested to be involved in a stepwise transfer of an oxidation hole from the flavin to the surface of the protein. Here, we investigated the effect of mutation of the fourth Trp on the DNA photorepair activity of Xenopus laevis (6-4)PL (Xl64) in bacterial cells. The photoreduction and photorepair properties of this mutant protein were independently characterized in vitro. Our results demonstrate that the mutation of the fourth Trp in Xl64 drastically impairs the DNA repair activity in cells and that this effect is due to the inhibition of the photoreduction process. We thereby show that the photoreductive formation of FADH- through the Trp tetrad is essential for the biological function of the animal (6-4)PL. The role of the Trp cascade, and of the fourth Trp in particular, is discussed.

[A Case of Central-Type Disc Herniation at the C7/T1 Level Presenting with Myelopathy].

In contrast to other levels of upper disc spaces, the Luschka joints are usually absent at the C7/T1 disc space. Therefore, it has been reported that the C7/T1 disc herniation is prone to herniate laterally rather than centrally. In this manuscript, we describe an extremely rare central-type disc herniation at the C7/T1 level presented with myelopathy. A 76-year-old man presented with a 20-day history of progressive gait disturbance. Physical examination revealed bilateral lower extremity hyperreflexia and mild foot numbness with no upper extremity motor weakness or sensory disturbance. Cervical magnetic resonance imaging(MRI)revealed severe spinal cord compression at the C7/T1 level caused by a central-type disc herniation. We removed the herniated disc and performed anterior fusion with a titanium box cage. Lower extremity numbness and weakness diminished rapidly. Three weeks later, cervical MRI showed a well-decompressed spinal cord and almost normal gait. We reevaluated the preoperative computed tomography of this patient and confirmed the absence of Luschka joints at the C7/T1 level. Although the condition is rare, clinicians should consider the possibility of C7/T1 disc herniation in patients with leg weakness or numbness but no or few hand-related symptoms.

Importance of Recognizing Carpal Tunnel Syndrome for Neurosurgeons: A Review.

Idiopathic carpal tunnel syndrome (CTS) is a common complaint, reflecting entrapment neuropathy of the upper extremity. CTS produces symptoms similar to those of other conditions, such as cervical spondylosis or ischemic or neoplastic intracranial disease. Because of these overlaps, patients with CTS are often referred to a neurosurgeon. Surgical treatment of CTS was started recently in our department. Through this experience, we realized that neurosurgeons should have an increased awareness of this condition so they can knowledgeably assess patients with a differential diagnosis that includes CTS and cervical spinal and cerebral disease. We conducted a literature review to gain the information needed to summarize current knowledge on the clinical, pathogenetic, and therapeutic aspects of CTS. Because the optimal diagnostic criteria for this disease are still undetermined, its diagnosis is based on the patient's history and physical examination, which should be confirmed by nerve conduction studies and imaging modalities such as magnetic resonance imaging and ultrasonography. Treatment methods include observation, medication, splinting, steroid injections, and surgical intervention. Understanding the clinical features and pathogenesis of CTS, as well as the therapeutic options available to treat it, is important for neurosurgeons if they are to provide the correct management of patients with this disease.

Acute Cerebral Artery Occlusion by a Calcified Embolus with False Patency Sign on Computed Tomographic Angiography.

Computed tomographic angiography (CTA) is a quick and accurate method in triage to determine recanalization therapies for acute ischemic stroke. To minimize delay in the start of recanalization therapies, performance of CTA immediately after unenhanced brain computed tomography (CT) is recommended as the minimum standard. However, there are some pitfalls related to image interpretation of CTA in acute stroke, such as false patency sign. We describe the case of a 66-year-old man who presented with acute middle cerebral artery (MCA) occlusion by a calcified embolus with false patency sign on CTA after coronary angiography. We misinterpreted the CTA image as a patent MCA, and unnecessary brain magnetic resonance imaging caused delay in the start of endovascular thrombectomy. Our findings suggest that calcified cerebral emboli can present with false patency sign on CTA. To avoid misinterpretation of the CTA image and start recanalization therapy as soon as possible, physicians should be aware of false patency sign, especially when unenhanced CT shows hyperdense emboli and CTA findings do not correspond with patients' symptoms in acute ischemic stroke.