Rehabilitation facilitates functional improvement following intravenous infusion of mesenchymal stem cells in the chronic phase of cerebral ischemia in rats.

The primary objective of this study was to investigate the potential facilitating effects of daily rehabilitation for chronic cerebral ischemia following the intravenous infusion of mesenchymal stem cells (MSC) in rats. The middle cerebral artery (MCA) was occluded by intraluminal occlusion using a microfilament (MCAO). Eight weeks after MCAO induction, the rats were used as a chronic cerebral ischemia model. Four experimental groups were studied: Vehicle group (medium only, no cells); Rehab group (vehicle + rehabilitation), MSC group (MSC only); and Combined group (MSC + rehabilitation). Rat MSCs were intravenously infused eight weeks after MCAO induction, and the rats received daily rehabilitation through treadmill exercise for 20 min. Behavioral testing, lesion volume assessment using magnetic resonance imaging (MRI), and histological analysis were performed during the observation period until 16 weeks after MCAO induction. All treated animals showed functional improvement compared with the Vehicle group; however, the therapeutic efficacy was greatest in the Combined group. The combination therapy is associated with enhanced neural plasticity shown with histological analysis and MRI diffusion tensor imaging. These findings provide behavioral evidence for enhanced recovery by combined therapy with rehabilitation and intravenous infusion of MSCs, and may form the basis for the development of clinical protocols in the future.

Triglyceride-glucose index predicts future chronic kidney disease development in all populations, including normotensive and isolated diastolic hypertension.

Hypertension and insulin resistance are established risk factors for chronic kidney disease. However, the association between chronic kidney disease and insulin resistance in detailed hypertension pattern groups such as isolated diastolic hypertension remains unclear. Triglyceride-glucose index has been noted as an indicator of insulin resistance. This study investigated the association between the triglyceride-glucose index and chronic kidney disease in four blood pressure groups: isolated diastolic hypertension, isolated systolic hypertension, systolic diastolic hypertension, and normotension. Using a database of 41,811 middle-aged men who had two or more annual health checkups from 2007 to 2019, those with chronic kidney disease at the first visit, antihypertensive/diabetes/dyslipidemia medication users, and incomplete data were excluded. Four groups were categorized using the 140/90 mmHg threshold. A COX proportional hazards model was used to assess the triglyceride-glucose index with incident chronic kidney disease. Participants were divided: isolated diastolic hypertension: 2207 (6.72%), isolated systolic hypertension: 2316 (7.06%), systolic-diastolic hypertension: 3299 (10.05%), normal: 24,996 (76.17%). The follow-up period was 6.78 years. Adjusted hazard ratios (HRs) and 95% CIs per unit increase in triglyceride-glucose index: isolated diastolic hypertension (HR = 1.31, 95% CI (1.06-1.62)), isolated systolic hypertension (HR = 1.36, 95% CI (1.12-1.64)), systolic-diastolic hypertension (HR = 1.40, 95% CI (1.19-1.64)), normal (HR = 1.18, 95% CI (1.09-1.28)). Triglyceride-glucose index is relevant for predicting chronic kidney disease development in all subtypes of hypertension. The results may lead to early prediction and prevention of the development of chronic kidney disease.

Predictors of procedural complications in balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is an effective treatment for inoperable chronic thromboembolic pulmonary hypertension, with good results reported for residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). However, BPA is associated with complications, such as pulmonary artery perforation and vascular injury, which can lead to critical pulmonary hemorrhage requiring embolization and mechanical ventilation. Furthermore, the risk factors for occurrence of complications in BPA are unclear; therefore, this study aimed to evaluate predictors of procedural complications in BPA. METHODS: In this retrospective study, we collected clinical data (patient characteristics, details of medical therapy, hemodynamic parameters, and details of the BPA procedure) from 321 consecutive sessions involving 81 patients who underwent BPA. Procedural complications were evaluated as endpoints. RESULTS: BPA for residual PH after PEA was performed in 141 sessions (43.9 %), which involved 37 patients. Procedural complications were observed in 79 sessions (24.6 %), including severe pulmonary hemorrhage requiring embolization in 29 sessions (9.0 % of all sessions). No patients experienced severe complications requiring intubation with mechanical ventilation or extracorporeal membrane oxygenation. Age ≥ 75 years and mean pulmonary artery pressure ≥ 30 mmHg were independent predictors of procedural complications. Residual PH after PEA was a significant predictor of severe pulmonary hemorrhage requiring embolization (adjusted odds ratio, 3.048; 95 % confidence interval, 1.042-8.914, p = 0.042). CONCLUSIONS: Older age, high pulmonary artery pressure, and residual PH after PEA increase the risk of severe pulmonary hemorrhage requiring embolization in BPA.

Balloon pulmonary angioplasty followed by pulmonary endarterectomy: Combination treatment for high-surgical-risk patients with chronic thromboembolic pulmonary hypertension.

OBJECTIVES: Our goal was to evaluate the combined effects of balloon pulmonary angioplasty (BPA) followed by pulmonary endarterectomy (PEA) to treat high-surgical-risk patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: This study included 58 patients with CTEPH who had pulmonary vascular resistance of ≥1000 dyn·s/cm5, mean pulmonary arterial pressure (mPAP) of ≥45 mmHg or mPAP of 38-44 mmHg with comorbidities. Of these, 21 patients underwent the combined therapy of BPA followed by PEA (BPA group) and 37 underwent direct PEA (non-BPA group). Preoperative and postoperative results were compared between the 2 groups. An early postoperative composite event comprised the postoperative use of extracorporeal membrane oxygenation or intra-aortic balloon pump, in-hospital death, rescue BPA, prolonged ventilation, tracheostomy, prolonged stay in the intensive care unit, deep sternal wound infection and cerebral infarction. RESULTS: Before the first intervention (before BPA or direct PEA), patients in the BPA group had a higher mPAP than those in the non-BPA group. After undergoing BPA before PEA, the BPA group demonstrated significantly decreased mPAP and pulmonary vascular resistance (43 vs 52 mmHg, P < 0.001; 636 vs 965 dyn·s/cm5, P = 0.003, respectively) and significantly increased cardiac output (4.1 vs 3.5 l/min, P = 0.041). Notably, the number of patients with the early postoperative composite event was significantly lower in the BPA group than in the non-BPA group (4.8% vs 35.1%, P = 0.011). CONCLUSIONS: Compared with direct PEA, the combination therapy of BPA followed by PEA can be a feasible and effective risk-reduction strategy for high-surgical-risk patients with CTEPH.

Association of the severity of vascular damage with discordance between the fractional flow reserve and non-hyperemic pressure ratios.

BACKGROUND: While there is a discordance between fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) in some cases, the mechanisms underlying these discordances have not yet been fully clarified. We examined whether vascular damage as assessed by measurement of the brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, or ankle brachial pressure index (ABI), a marker of atherosclerotic arterial stenosis, might be associated with their discordances. METHODS: FFR and NHPRs were measured in 283 consecutive patients (69 ±â€¯10 years old). Based on previously established cut-off values of the two markers (i.e. +/- = FFR ≤/> 0.80 or =NHPRs ≤/> 0.89), the study participants were divided into four groups (the + and - signs denoting "predictive of significant stenosis" and "not predictive of significant stenosis," respectively): the FFR+/NHPRs+ group (n = 124), FFR-/NHPRs+ group (n = 16), FFR+/NHPRs- group(n = 65), and FFR-/NHPRs- group (n = 78). The baPWV and ABI were also measured in all the participants, and values of <2000 cm/s and ≥1.00 of the baPWV and ABI, respectively, were considered as representing relatively less advanced atherosclerotic systemic vascular damage. RESULTS: The prevalence of subjects with ABI ≥1.00 was higher in the FFR+/NHPRs- group than in the FFR-/NHPRs- group (p < 0.05). When the study subjects were divided into 2 groups, namely, the FFR+/NHPRs- group and the combined group, the prevalence of ABI ≥1.00 and that of baPWV <2000 cm/s were higher in the FFR+/NHPRs- group as compared with those in the combined group (p < 0.05). The results of binary logistic regression analysis demonstrated that ABI ≥1.00 was associated with a significant odds ratio (2.34, p < 0.05) for the FFR+/NHPRs- discordance. CONCLUSION: The FFR+/NHPRs- discordance appears to be observed in patients with relatively less advanced atherosclerotic systemic vascular damage. Thus, ABI ≥1.00 may be a marker of the presence of the FFR+/NHPRs- discordance.

Diagnostic performance of intraoperative cone beam computed tomography compared with postoperative magnetic resonance imaging for detecting hemorrhagic transformation after endovascular treatment following large vessel occlusion.

OBJECTIVES: Early detection of hemorrhagic transformation (HT) in patients with large vessel occlusion (LVO) after endovascular treatment is important for postoperative patient management. We investigated the diagnostic performance of intraoperative cone beam computed tomography (CBCT) with reference standard magnetic resonance imaging (MRI) for detecting HT. MATERIALS AND METHODS: Consecutive patients with LVO treated by endovascular treatment who underwent intraoperative CBCT and postoperative MRI were included. Two observers evaluated all images for the presence of HT. Sensitivity and specificity for detecting HT were calculated with MRI as reference standard. The observers classified HT according to the European Cooperative Acute Stroke Study (ECASS). Inter-method and inter-rater agreement for the detection of HT and for the ECASS classification were assessed using kappa or weighted Brennan-Prediger (wBP) statistics. RESULTS: Images of 106 procedures (94 for anterior circulation) were analyzed. The sensitivity and specificity for detecting HT on CBCT were 0.77 and 0.83, respectively, for all procedures and 0.83 and 0.8, respectively, for anterior circulation. The inter-method agreement for HT detection (κ = 0.63 overall, κ = 0.69 anterior circulation) and ECASS classification (wBP = 0.67 overall, wBP = 0.77 anterior circulation) were substantial. The inter-rater agreement for HT detection (κ = 0.87 overall, κ = 0.85 anterior circulation) and for ECASS classification (wBP = 0.95 overall, wBP = 0.92 anterior circulation) were almost perfect. CONCLUSIONS: The diagnostic performance of CBCT for the detection of HT in stroke patients treated for LVO was acceptable with excellent inter-rater agreement. Intraoperative CBCT may be useful to trigger early interventions if HT is detected, although detailed classifications of HT may be difficult.

Subclavian Artery Flow Dynamics Evaluated by Analytical Intraoperative Indocyanine Green Videoangiography During Surgical Treatment of Thoracic Outlet Syndrome: A Case Series.

BACKGROUND: Indocyanine green (ICG) videoangiography is rarely used during the surgical treatment of thoracic outlet syndrome (TOS). OBJECTIVE: To evaluate subclavian artery (SA) flow dynamics using the analytical ICG videoangiography during TOS surgeries. METHODS: We examined patients with neurogenic TOS who received surgical treatment and whose SA blood flow at the interscalene space was evaluated using ICG videoangiography equipped with an analytical function (FLOW800). Anterior scalenectomy with or without middle scalenectomy and first rib resection were conducted for decompression of the brachial plexus. ICG videoangiography was performed before and after decompression of the brachial plexus. After acquisition of grayscale and color-coded maps, a region of interest was placed in the SA to obtain time-intensity diagrams. Maximum intensity (MI), rise time (RT), and blood flow index (BFi) were calculated from the diagram, in arbitrary intensity (AI) units. We compared values before and after decompression. Comparisons of the three parameters before and after decompression were assessed statistically using the paired t-tests and Wilcoxon signed-rank test. RESULTS: We evaluated nine procedures in consecutively presenting patients. The observed mean values of MI, RT, and BFi before decompression were 174.1 ± 61.5 AI, 5.2 ± 1.1 s, and 35.2 ± 13.5 AI/s, respectively, and the observed mean values of MI, RT, and BFi after decompression were 299.3 ± 167.4 AI, 6.6 ± 0.8 s, and 44.6 ± 28.3 AI/s, respectively. These parameters showed higher values after decompression than before decompression, and the increase in MI and RT was statistically significant (P < .05). CONCLUSION: ICG videoangiography allows semiquantitative evaluation of hemodynamic changes during TOS surgery. A marked decrease in the velocity of SA flow was observed after decompression.

Multimodal treatment including lumbar facet joint denervation for severe low back pain in patients with neuromuscular disorders.

BACKGROUND: Severe low back pain (LBP) is an occasional complaint in patients with neuromuscular disorders (NMDs). Accurate diagnosis and treatment are required to manage LBP; however, the precise pathophysiology differs for each patient. This study aimed to evaluate the efficacy of lumbar facet joint denervation (FJD) and adjunctive modalities in the treatment of LBP in patients with NMD-associated kyphoscoliosis. METHODS: A total of 16 patients (22 sites) with NMD (bilateral, n = 6; unilateral, n = 10) and LBP treated with lumbar FJD were evaluated. The patients were divided into two groups: those treated with FJD alone (group 1) and those treated with multimodal treatment, including FJD along with radiofrequency ablation for sacroiliac joint pain, piriform muscle block, botulinum toxin injection into the paraspinal muscles, spinal cord stimulation, or any of their combinations (group 2). All patients were followed up for 48 weeks postoperatively. The two groups were compared with respect to the duration required for improvements in LBP by more than 50% (numerical rating scale ≤ 5). RESULTS: There was no significant difference between the groups regarding the age, duration since the onset of Parkinson's syndrome, and radiographic analysis. The effective period of improved pain was greater in group 2 than in group 1 (30.7 vs. 8.4 weeks, P < 0.01). CONCLUSIONS: Multimodal treatment including FJD is safe and relatively effective in patients with NMD-associated kyphoscoliosis. Hence, it is a potential substitute for conventional spinal fixation surgery, which has a higher risk of complications.

Association of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 With Angiotensin II Type 1 Receptor Impacts Mitochondrial Quality Control, Offering Promise for the Treatment of Vascular Senescence.

Lectin-like oxidized low-density lipoprotein (ox-LDL) causes vascular senescence and atherosclerosis. It has been reported that ox-LDL scavenger receptor-1 (LOX-1) is associated with the angiotensin II type 1 receptor (AT1R). While mitochondria play a crucial role in the development of vascular senescence and atherosclerosis, they also undergo quality control through mitochondrial dynamics and autophagy. The aim of this study was to investigate (1) whether LOX-1 associates with AT1R, (2) if this regulates mitochondrial quality control, and (3) whether AT1R inhibition using Candesartan might ameliorate ox-LDL-induced vascular senescence. We performed in vitro and in vivo experiments using vascular smooth muscle cells (VSMCs), and C57BL/6 and apolipoprotein E-deficient (ApoE KO) mice. Administration of oxidized low-density lipoprotein (ox-LDL) to VSMCs induced mitochondrial dysfunction and cellular senescence accompanied by excessive mitochondrial fission, due to the activation of fission factor Drp1, which was derived from the activation of the Raf/MEK/ERK pathway. Administration of either Drp1 inhibitor, mdivi-1, or AT1R blocker candesartan attenuated these alterations. Electron microscopy and immunohistochemistry of the co-localization of LAMP2 with TOMM20 signal showed that AT1R inhibition also increased mitochondrial autophagy, but this was not affected by Atg7 deficiency. Conversely, AT1R inhibition increased the co-localization of LAMP2 with Rab9 signal. Moreover, AT1R inhibition-induced mitochondrial autophagy was abolished by Rab9 deficiency, suggesting that AT1R signaling modulated mitochondrial autophagy derived from Rab9-dependent alternative autophagy. Inhibition of the Raf/MEK/ERK pathway also decreased the excessive mitochondrial fission, and Rab9-dependent mitochondrial autophagy, suggesting that AT1R signaling followed the Raf/MEK/ERK axis modulated both mitochondrial dynamics and autophagy. The degree of mitochondrial dysfunction, reactive oxygen species production, vascular senescence, atherosclerosis, and the number of fragmented mitochondria accompanied by Drp1 activation were all higher in ApoE KO mice than in C57BL/6 mice. These detrimental alterations were successfully restored, and mitochondrial autophagy was upregulated with the administration of candesartan to ApoE KO mice. The association of LOX-1 with AT1R was found to play a crucial role in regulating mitochondrial quality control, as cellular/vascular senescence is induced by ox-LDL, and AT1R inhibition improves the adverse effects of ox-LDL.

Efficacy and safety of balloon pulmonary angioplasty for residual pulmonary hypertension after pulmonary endarterectomy.

BACKGROUND: Pulmonary endarterectomy (PEA) is the standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH), although some patients may experience residual pulmonary hypertension (PH). It is unclear whether balloon pulmonary angioplasty (BPA) is effective for residual PH after PEA. This study aimed to compare the BPA outcomes between patients with residual PH after PEA and those with inoperable CTEPH. METHODS: This retrospective study compared BPA for residual PH after PEA (25 patients, 101 BPA sessions) and BPA alone for inoperable CTEPH (21 patients, 89 BPA sessions). All patients underwent right heart catheterisation and functional and laboratory tests before PEA or before and after BPA. RESULTS: There was no difference in the number of BPA sessions per patient (4.0 ± 1.9 vs. 4.2 ± 1.9, p = 0.671). No significant differences were observed with respect to the mean pulmonary artery pressure (23.6 ± 9.1 vs. 21.9 ± 5.7 mmHg, p = 0.44), pulmonary vascular resistance (3.7 ± 0.5 vs. 2.8 ± 1.2 Wood units, p = 0.14), 6-min walking distance (392.1 ± 117.7 vs. 452.4 ± 90.1 m, p = 0.096), and World Health Organization functional class (I/II/III/IV: 14/11/0/0 vs. 9/12/0/0, p = 0.375). Severe haemoptysis requiring embolisation was more common in the PH after PEA group (16.0% vs. 5.4%, p = 0.018). However, no patients required mechanical ventilation or extracorporeal membrane oxygenation, and there were no procedural deaths. CONCLUSION: Although BPA might be effective for residual PH after PEA, it was associated with a high rate of haemoptysis.

Estrogen Plays a Crucial Role in Rab9-Dependent Mitochondrial Autophagy, Delaying Arterial Senescence.

Background The risk of cardiovascular disease is known to increase after menopause. Mitochondria, which undergo quality control via mitochondrial autophagy, play a crucial role in the regulation of cellular senescence. The aim of this study was to investigate whether the effect of estrogen-mediated protection from senescence on arteries is attributed to the induction of mitochondrial autophagy. Methods and Results We used human umbilical vein cells, vascular smooth muscle cells, and 12-week-old female C57BL/6 mice. The administration of 17ß-estradiol (E2) to cells inhibited cellular senescence and mitochondrial dysfunction. Furthermore, E2 increased mitochondrial autophagy, maintaining mitochondrial function, and retarding cellular senescence. Of note, E2 did not modulate LC3 (light chain 3), and ATG7 (autophagy related 7) deficiency did not suppress mitochondrial autophagy in E2-treated cells. Conversely, E2 increased the colocalization of Rab9 with LAMP2 (lysosomal-associated membrane protein 2) signals. The E2-mediated effects on mitochondrial autophagy were abolished by the knockdown of either Ulk1 or Rab9. These results suggest that E2-mediated mitochondrial autophagy is associated with Rab9-dependent alternative autophagy. E2 upregulated SIRT1 (sirtuin 1) and activated LKB1 (liver kinase B1), AMPK (adenosine monophosphate-activated protein kinase), and Ulk1, indicating that the effect of E2 on the induction of Rab9-dependent alternative autophagy is mediated by the SIRT1/LKB1/AMPK/Ulk1 pathway. Compared with the sham-operated mice, ovariectomized mice showed reduced mitochondrial autophagy and accelerated mitochondrial dysfunction and arterial senescence; these detrimental alterations were successfully rescued by the administration of E2. Conclusions We showed that E2-induced mitochondrial autophagy plays a crucial role in the delay of vascular senescence. The Rab9-dependent alternative autophagy is behind E2-induced mitochondrial autophagy.

Intravenous infusion of auto serum-expanded autologous mesenchymal stem cells in spinal cord injury patients: 13 case series.

BACKGROUND: Although spinal cord injury (SCI) is a major cause of disability, current therapeutic options remain limited. Recent progress in cellular therapy with mesenchymal stem cells (MSCs) has provided improved function in animal models of SCI. We investigated the safety and feasibility of intravenous infusion of MSCs for SCI patients and assessed functional status after MSC infusion. METHODS: In this phase 2 study of intravenous infusion of autologous MSCs cultured in auto-serum, a single infusion of MSCs under Good Manufacturing Practice (GMP) production was delivered in 13 SCI patients. In addition to assessing feasibility and safety, neurological function was assessed using the American Spinal Injury Association Impairment Scale (ASIA), International Standards for Neurological and Functional Classification of Spinal Cord (ISCSCI-92). Ability of daily living was assessed using Spinal Cord Independence Measure (SCIM-III). The study protocol was based on advice provided by the Pharmaceuticals and Medical Devices Agency in Japan. The trial was registered with the Japan Medical Association (JMA-IIA00154). RESULTS: No serious adverse events were associated with MSC injection. There was neurologic improvement based on ASIA grade in 12 of the 13 patients at six months post-MSC infusion. Five of six patients classified as ASIA A prior to MSC infusion improved to ASIA B (3/6) or ASIA C (2/6), two ASIA B patients improved to ASIA C (1/2) or ASIA D (1/2), five ASIA C patients improved and reached a functional status of ASIA D (5/5). Notably, improvement from ASIA C to ASIA D was observed one day following MSC infusion for all five patients. Assessment of both ISCSCI-92, SCIM-III also demonstrated functional improvements at six months after MSC infusion, compared to the scores prior to MSC infusion in all patients. CONCLUSION: While we emphasize that this study was unblinded, and does not exclude placebo effects or a contribution of endogenous recovery or observer bias, our observations provide evidence supporting the feasibility, safety and functional improvements of infused MSCs into patients with SCI.

Coronary artery perforation secondary to lifesaving pericardiocentesis for cardiac tamponade: a case report.

BACKGROUND: Pericardiocentesis is frequently performed when fluid needs to be removed from the pericardial sac, for both therapeutic and diagnostic purposes, however, it can still be a high-risk procedure in inexperienced hands and/or an emergent setting. CASE PRESENTATION: A 78-year-old male made an emergency call complaining of the back pain. When the ambulance crew arrived at his home, he was in a state of shock due to cardiac tamponade diagnosed by portable echocardiography. The pericardiocentesis was performed using a puncture needle on site, and the patient was immediately transferred to our hospital by helicopter. Contrast-enhanced computed tomography showed a small protrusion of contrast media on the inferior wall of the left ventricle, suggesting cardiac rupture due to acute myocardial infarction. Emergency coronary angiography was then performed, which confirmed occlusion of the posterior descending branch of the left circumflex coronary artery. In addition, extravasation of contrast medium due to coronary artery perforation was observed in the acute marginal branch of the right coronary artery. We considered that coronary artery perforation had occurred as a complication of the pericardial puncture. We therefore performed transcatheter coil embolization of the perforated branch, and angiography confirmed immediate vessel sealing and hemostasis. After the procedure, the patient made steady progress without a further increase in pericardial effusion, and was discharged on the 50th day after admission. CONCLUSIONS: When performing pericardial drainage, it is important that the physician recognizes the correct procedure and complications of pericardiocentesis, and endeavors to minimize the occurrence of serious complications. As with the patient presented, coil embolization is an effective treatment for distal coronary artery perforation caused by pericardiocentesis.

A Case of Severe Common Carotid Artery Stenosis Who Developed Cerebellar Infarction after Cervical Irradiation.

Objective: We report a case of cerebellar infarction caused by radiation-induced common carotid artery stenosis. Case Presentation: The patient was a 72-year-old man who underwent irradiation for hypopharyngeal carcinoma 13 years ago. He was referred for asymptomatic left common carotid artery stenosis, but was brought to our hospital by ambulance with transient dysarthria and right facial dysesthesia 2 days after referral. Magnetic resonance imaging (MRI) revealed acute infarction in the left cerebellar hemisphere, and digital subtraction angiography (DSA) demonstrated that the blood flow in the left internal carotid artery perfused the left posterior inferior cerebellar artery (PICA) retrogradely through the left posterior communicating artery. The patient underwent carotid artery stenting (CAS) for left common carotid artery stenosis and blood flow in the left PICA improved; however, in-stent restenosis was revealed during follow-up. Percutaneous transluminal angioplasty (PTA) for in-stent restenosis was performed 9 months after the surgery. Conclusion: We reported a rare case of ischemia in the PICA area caused by radiation-induced common carotid artery stenosis. Although CAS is recommended for the treatment of radiation-induced carotid artery stenosis, careful treatment and follow-up are needed to prevent perioperative complications and detect in-stent restenosis after CAS.

Clinical predictors of surgical outcomes of severe carpal tunnel syndrome patients: utility of palmar stimulation in a nerve conduction study.

BACKGROUND: Carpal tunnel syndrome is a common peripheral nerve compression disorder. However, there is no established opinion regarding the predictors of symptom improvement after surgery. This study aimed to identify the predictors of surgical outcomes of severe carpal tunnel syndrome patients. METHODS: In the patients who underwent a carpal tunnel syndrome surgery, we selected the patients who had a preoperative Bland's classification of grade 5 or 6, and assessed for the changes in Bland's classification grade before and after surgery. Those who showed improvement from preoperative grades 5-6 to postoperative grades 1-4 comprised the improvement group. In contrast, those who did not show improvement and had postoperative grades 5 or 6 comprised the non-improvement group. In a nerve conduction study, amplitudes of the compound muscle action potential and sensory nerve action potential of the palms were assessed between the improvement and non-improvement groups. RESULTS: Among the 60 hands of 46 patients who had a preoperative Bland's classification of grade 5 or 6, 49 hands of 37 patients comprised the improvement group, and 11 hands of 9 patients comprised the non-improvement group. The amplitudes of the compound muscle action potential and sensory nerve action potential of the palms before surgery were significantly higher in the improvement group. The degree of improvement in Bland's classification grade was correlated with the degree of clinical symptom improvement. CONCLUSIONS: Amplitudes of compound muscle action potential and sensory nerve action potential before surgery induced by palmar stimulation can predict improvements in nerve conduction study scores and clinical findings after surgical treatment.

Spontaneous cerebrospinal fluid otorrhea and pneumocephalus on the contralateral side of the previous cranial surgery.

BACKGROUND: Cerebrospinal fluid (CSF) leaks and pneumocephalus commonly occur due to head trauma or surgical procedures. Spontaneous CSF (sCSF) leaks, however, occur without any clear etiology and are relatively uncommon. CASE DESCRIPTION: An 84-year-old woman presented with the right-sided otorrhea. The patient had a history of a ventriculoperitoneal shunt placement following a subarachnoid hemorrhage treated by clip ligation of a left-sided ruptured cerebral aneurysm 7 years before presentation, with shunt catheter ligation after evidence of intraventricular pneumocephalus 6 years before presentation. At admission, computed tomography (CT) imaging of the head showed enlargement of the lateral ventricles, a right mastoid fluid collection, and a defect of the superior wall of the right petrous bone. We performed a right temporal craniotomy for the repair of the CSF leak. Intraoperatively, it was noted that temporal lobe parenchyma herniated into the mastoid air cells through lacerated dura and a partially defective tegmen mastoideum. The leak point was successfully obliterated with a pericranial graft and reinforced by a collagen sheet and fibrin glue. There was no recurrence of otorrhea postoperatively. CONCLUSION: This report presents a very unique case of a patient with a CSF leak and pneumocephalus occurring on the contralateral side of a previous cranial surgery. We accurately identified the defect site with CT imaging and repaired the CSF leak by temporal craniotomy. Awareness of the mechanisms by which sCSF leaks can be caused by aberrant arachnoid granulations is imperative for neurosurgeons.

Estrogen-SIRT1 Axis Plays a Pivotal Role in Protecting Arteries Against Menopause-Induced Senescence and Atherosclerosis.

AIM: Menopause causes arterial senescence and atherosclerotic development through decrease of estrogen. Recently, histone deacetylase SIRT1 has been reported to have protective effects against arterial senescence and atherosclerosis. However, the relationship between estrogen and SIRT1 in the context of menopause-induced arterial senescence is not well understood. The present study aims to investigate whether SIRT1 is involved in the etiology of menopause-induced arterial senescence and atherosclerotic development. METHODS: Twelve-week old female apolipoprotein E-knockout (ApoE-KO) mice underwent ovariectomy (OVX) or sham surgery. RESULTS: SIRT1 expression and endothelial nitric oxide synthase (eNOS) activation in the aorta were significantly lower in OVX mice than they were in sham mice (OVX vs. sham, n=5 per group). Senescence-associated ß-galactosidase activity, protein expression of Ac-p53 and PAI-1, and aortic atherosclerosis lesions were significantly greater in OVX mice than they were in sham mice. Administration of 17ß-estradiol (E2) for eight weeks to OVX mice restored aortic SIRT1 expression, activated eNOS, and retarded OVX-induced arterial senescence and atherosclerotic development (E2 vs. control, n=5 per group). The effects of E2 on SIRT1 upregulation, anti-senescence and anti-atherosclerosis were attenuated by administration of a SIRT1 inhibitor, sirtinol. In vitro experiment using human endothelial cells demonstrated that E2 also increased SIRT1 expression and retarded oxidized low density lipoprotein-induced premature senescence, which were also abolished by sirtinol. These results suggested that estrogen modulated arterial senescence and atherosclerosis through SIRT1. Additionally a selective estrogen receptor modulator (SERM), bazedoxifene, also augmented SIRT1 and inhibited arterial senescence and atherosclerotic development (SERM vs. control, n=3 per group). CONCLUSIONS: Downregulation of SIRT1 causes OVX-induced arterial senescence and atherosclerosis in ApoE-KO mice. Administration of estrogen or SERM enables OVX mice to restore these alterations by SIRT1 induction.

Preoperative Light Transmission Aggregometry Values Predict for Thromboembolic Complications After Stent-Assisted Coil Embolization.

OBJECTIVE: Risk control of thromboembolic complications (TECs) during stent-assisted coil embolization (SACE) for unruptured intracranial aneurysms (UIAs) is crucial for satisfactory treatment outcomes. We retrospectively evaluated the data from our cohort of SACE for UIAs to analyze the role of anatomical, clinical, and stent type-related factors to determine the optimal preoperative values of light transmission aggregometry (LTA) for TEC prevention. METHODS: From July 2015 to May 2018, we retrospectively analyzed the data from 132 patients with SACE-treated UIAs at our hospital. Data regarding the aneurysm location, maximum diameter, stent type used, preoperative LTA value, and ischemic and hemorrhagic complications were collected. Aspirin 100 mg and clopidogrel 75 mg were started 7 days before surgery, with a "boost" dose (an additional 75 mg of clopidogrel for an LTA value >60%) added after August 2016 to address clopidogrel resistance. After multivariate analysis, we developed our original combined parameter termed the thromboembolic predictor (TEP). Receiver operating characteristic (ROC) analysis for TEP and each significant variable was performed. RESULTS: TECs were confirmed in 5 of the 132 patients (3.8%) and hemorrhagic complications in 9 of the 132 patients (6.8%). From the multivariate analysis results, the LTA value and maximum diameter were chosen as significant variables and included in the TEP. ROC analysis of the LTA value revealed a sensitivity and specificity of 0.866 and 0.600, respectively (area under the curve, 0.747), with a cutoff of 62%. TEP permitted the establishment of an optimal LTA value according to the aneurysm maximum diameter to predict for TECs. The complication rate for the Neuroform EZ, Enterprise, Neuroform Atlas, and LVIS stents was 2.9%, 10.5%, 1.4%, and 14.3%, respectively. CONCLUSIONS: The preoperative LTA value contributes to the prediction of TECs after SACE for UIAs. The TEP (relating the LTA cutoff to aneurysm size) allows for improved antiplatelet therapy adjustment before SACE to reduce TECs.

Intravenous infusion of mesenchymal stem cells improves impaired cognitive function in a cerebral small vessel disease model.

Cerebral small vessel disease (CSVD) is not only a cause of vascular dementia (VD) but also a contributing factor to Alzheimer's disease (AD). The essential pathological feature of CSVD is the disruption of blood-brain barrier (BBB). Dysfunction of BBB due to degeneration of both endothelial cells and pericytes in capillaries leads to neuronal damage and progressive brain atrophy. Moreover, deterioration of amyloid-ß (Aß) clearance due to the failure of the transvascular BBB transport system results in accumulation of Aß in the brain. Intravenous infusion of mesenchymal stem cells (MSCs) elicits functional recovery in experimental models including stroke and spinal cord injury. One effect of MSCs is to restore disrupted BBB through remodeling of microvasculature. Using spontaneously hypertensive rats (stroke-prone) with impaired cognitive function as a CSVD model, we have shown that infused MSCs has a therapeutic effect for cognitive function. Restoration of BBB function via remodeling of microvasculature and inhibition of Aß accumulation could inhibit progressive brain atrophy and lead to restore cognitive dysfunction. Gene expression analysis indicated that infused MSCs activates both transforming growth factor-ß and angiopoietin 1 signaling pathways and promotes the remodeling of microvasculature. Thus, infused MSCs may represent a novel therapy for both VD and AD.

Separation between the chest wall and subpleural lung lesions: A two-step method to preoperatively exclude invasion or focal pleural adhesion by multidetector computed tomography.

PURPOSE: To develop and assess a non-invasive two-step method for evaluating the relationship between the parietal pleura and peripheral pulmonary lesions to preoperatively exclude invasion or focal pleural adhesion by multidetector computed tomography (CT). METHODS: Twenty-six patients with pulmonary peripheral lesions who underwent surgical lung resection between May and December 2017 were enrolled in this study. Routine CT was performed in the inspiratory phase in the supine position. Additional CT examinations were performed both in inspiratory and expiratory phases in the affected-side-up lateral position. Axial, sagittal, and coronal images were reconstructed from the CT data. In the first-step analysis, we evaluated the separation between the chest wall and subpleural lung lesions (separation) by comparing inspiratory- and expiratory-phase images obtained in the affected-side-up lateral position. When the separation was absent, we performed a second-step analysis, where we compared images obtained in the supine position during routine CT with those obtained in the affected-side-up lateral position and subsequently assessed the presence and absence of the separation. RESULTS: In the first-step analysis, the separation was observed in 21 lesions, which were categorised as showing "no invasion" or "no focal adhesion" on the basis of histological findings. After the second-step analysis, the separation was absent in three lesions and present in two; the latter two lesions were categorised as showing "no invasion" or "no focal adhesion" on the basis of operative and histological findings. Of the three lesions that did not exhibit the separation in either step of the analysis, two were diagnosed as exhibiting parietal pleural invasion on the basis of histological findings, while the third was categorised as showing "no invasion" or "no focal adhesion" on the basis of operative and histological findings. The sensitivity, specificity, positive and negative predictive values, and accuracy of this two-step method were 96% (95% confidence interval [CI]: 79-100%), 100% (95% CI: 16-100%), 100%, 67% (95% CI: 23-93%), and 96% (95% CI: 80-100%), respectively. CONCLUSIONS: Our two-step method is especially useful for excluding the parietal pleural involvement of peripheral pulmonary lesions. Even when the separation between the chest wall and subpleural lung lesions was limited, the change in position was useful for observing the separation and excluding parietal pleural involvement. This novel two-step method also has the advantage of being simple, cost-effective, and universally available.