Association between Carotid Bifurcation Angle and Vulnerable Plaque Volume Using Black Blood Magnetic Resonance Imaging.

The morphology of the internal carotid artery (ICA) bifurcation is increasingly being recognized as the cause of atherosclerosis and vulnerable plaque leading to cerebral infarction. In this study, we investigated the relationship between carotid bifurcation angle and carotid plaque volume evaluated using black blood magnetic resonance imaging (BB-MRI). Among the 90 patients who underwent revascularization for atherosclerotic symptomatic carotid stenosis between April 2016 and October 2022 using BB-MRI, carotid plaque was evaluated in 57 patients. Relative overall signal intensity (roSI) was defined as the signal intensity of the plaque on T1-weighted images relative to the signal intensity of the sternocleidomastoid muscle in the same slice as the common carotid bifurcation. Regions showing roSI ≥ 1.0 were defined as plaque, and the plaque volume and relative plaque volume were measured from roSI ≥1.0 to ≥2.0 in 0.1 increments. We calculated the angles between the common carotid artery (CCA) and the ICA and between the CCA and the external carotid artery (ECA) on magnetic resonance angiography. We classified two groups according to carotid bifurcation angles based on the ICA angle: Group A = <35° and Group B = ≥35°. Compared with Group A (n = 42), Group B (n = 15) showed a greater relative plaque volume between roSI ≥ 1.3 and roSI ≥ 1.5. A significant correlation was identified between relative plaque volume with roSI ≥ 1.4 and ICA angle (p = 0.049). Vulnerable plaque was significantly more frequent in the group with an ICA angle of ≥35. Moreover, the ICA angle was significantly greater in patients with a roSI of ≥1.4.

Preoperative elevated eosinophils in peripheral blood for prediction of postoperative recurrence of chronic subdural hematoma.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a common neurological disease with a significant postoperative recurrence rate. There are numerous reported studies of the development of CSDH. In recent years, fibrinolysis, angiogenesis, and inflammation have all been identified as relevant factors in the development of CSDH. While several authors have reported risk factors associated with CSDH recurrence, differential blood count of leukocytes has not yet been discussed. Therefore, in this study the authors aimed to retrospectively investigate the association between differential blood leukocyte count and the rate of CSDH recurrence. METHODS: The authors retrospectively reviewed 476 patients with 529 CSDHs who underwent surgery at a single institution between January 2011 and December 2021. After exclusion of patients who had not undergone a differential blood test of leukocytes preoperatively, CSDHs in 517 cerebral hemispheres of 466 patients were included in the study. Peripheral blood eosinophil counts ≥ 100/µL were considered eosinophil rich. RESULTS: CSDHs in 494 cerebral hemispheres of 445 patients were followed up postoperatively for at least 3 months or until resolution indicated by CSDH disappearance. Postoperative recurrence of CSDH was observed in 46 cerebral hemispheres (9.3%). Among the preoperative differential blood counts of all leukocytes, eosinophils alone were significantly associated with CSDH recurrence (median [IQR] 76/µL [30-155/µL] vs 119/µL [39-217/µL]; p = 0.03). Multivariable regression analysis showed thrombocytopenia (adjusted OR [aOR] 5.23, 95% CI 1.85-14.79; p = 0.002), use of anticoagulant drugs (aOR 2.51, 95% CI 1.17-5.38; p = 0.02), hematoma volume (10 mL per increase) (aOR 1.08, 95% CI 1.00-1.16; p = 0.04), and eosinophil-rich peripheral blood (aOR 2.22, 95% CI 1.17-4.23; p = 0.02) were all independent predictors for CSDH recurrence. CONCLUSIONS: This study showed that preoperative peripheral blood eosinophil count was an independent risk factor for CSDH recurrence. Therefore, patients with CSDH who have elevated eosinophils preoperatively in peripheral blood require careful follow-up.

Single mutation makes Escherichia coli an insect mutualist.

Microorganisms often live in symbiosis with their hosts, and some are considered mutualists, where all species involved benefit from the interaction. How free-living microorganisms have evolved to become mutualists is unclear. Here we report an experimental system in which non-symbiotic Escherichia coli evolves into an insect mutualist. The stinkbug Plautia stali is typically associated with its essential gut symbiont, Pantoea sp., which colonizes a specialized symbiotic organ. When sterilized newborn nymphs were infected with E. coli rather than Pantoea sp., only a few insects survived, in which E. coli exhibited specific localization to the symbiotic organ and vertical transmission to the offspring. Through transgenerational maintenance with P. stali, several hypermutating E. coli lines independently evolved to support the host's high adult emergence and improved body colour; these were called 'mutualistic' E. coli. These mutants exhibited slower bacterial growth, smaller size, loss of flagellar motility and lack of an extracellular matrix. Transcriptomic and genomic analyses of 'mutualistic' E. coli lines revealed independent mutations that disrupted the carbon catabolite repression global transcriptional regulator system. Each mutation reproduced the mutualistic phenotypes when introduced into wild-type E. coli, confirming that single carbon catabolite repression mutations can make E. coli an insect mutualist. These findings provide an experimental system for future work on host-microbe symbioses and may explain why microbial mutualisms are omnipresent in nature.

Incidence and clinical characteristics of spinal arteriovenous shunts: hospital-based surveillance in Okayama, Japan.

OBJECTIVE: There have been no accurate surveillance data regarding the incidence rate of spinal arteriovenous shunts (SAVSs). Here, the authors investigate the epidemiology and clinical characteristics of SAVSs. METHODS: The authors conducted multicenter hospital-based surveillance as an inventory survey at 8 core hospitals in Okayama Prefecture between April 1, 2009, and March 31, 2019. Consecutive patients who lived in Okayama and were diagnosed with SAVSs on angiographic studies were enrolled. The clinical characteristics and the incidence rates of each form of SAVS and the differences between SAVSs at different spinal levels were analyzed. RESULTS: The authors identified a total of 45 patients with SAVSs, including 2 cases of spinal arteriovenous malformation, 5 cases of perimedullary arteriovenous fistula (AVF), 31 cases of spinal dural AVF (SDAVF), and 7 cases of spinal epidural AVF (SEAVF). The crude incidence rate was 0.234 per 100,000 person-years for all SAVSs including those at the craniocervical junction (CCJ) level. The incidence rate of SDAVF and SEAVF combined increased with advancing age in men only. In a comparative analysis between upper and lower spinal SDAVF/SEAVF, hemorrhage occurred in 7/14 cases (50%) at the CCJ/cervical level and in 0/24 cases (0%) at the thoracolumbar level (p = 0.0003). Venous congestion appeared in 1/14 cases (7%) at the CCJ/cervical level and in 23/24 cases (96%) at the thoracolumbar level (p < 0.0001). CONCLUSIONS: The authors reported detailed incidence rates of SAVSs in Japan. There were some differences in clinical characteristics of SAVSs in the upper spinal levels and those in the lower spinal levels.

An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke.

BACKGROUND: Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. METHODS: We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. RESULTS: Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p < 0.001) and higher extent of NETosis (p = 0.006). Restricted mean survival time analysis revealed that older thrombi were associated with longer puncture-to-reperfusion times (difference: 15.6 minutes longer for older thrombi, p = 0.002). This association remained significant even after adjustment for erythrocyte content and the extent of NETosis (adjusted difference: 10.8 minutes, 95% confidence interval [CI]: 0.6-21.1 minutes, p = 0.039). Compared with fresh thrombi, older thrombi required more device passes before reperfusion (p < 0.001) and were associated with poorer functional outcomes (adjusted common odds ratio: 0.49; 95% CI: 0.24-0.99). CONCLUSION: An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

Variations and management for patients with craniocervical junction arteriovenous fistulas: Comparison of dural, radicular, and epidural arteriovenous fistulas.

BACKGROUND: Craniocervical junction arteriovenous fistulas (CCJAVFs) are known to be rare, but variations and clinical behaviors remain controversial. METHODS: A total of 11 CCJAVF patients (M: F=9:2, age 54-77 years) were investigated. Based on the radiological and intraoperative findings, they were categorized into three types: dural AVF (DAVF), radicular AVF (RAVF), and epidural AVF (EDAVF). RESULTS: There were four symptomatic patients (subarachnoid hemorrhage in two, myelopathy in one, and tinnitus in one) and seven asymptomatic patients in whom coincidental CCJAVFs were discovered on imaging studies for other vascular diseases (arteriovenous malformation in one, intracranial DAVF in two, ruptured cerebral aneurysm in two, and carotid artery stenosis in two). Of these 11 patients, 2 (18.2%) had multiple CCJAVFs. Of 14 lesions, the diagnoses were DAVF in 5, RAVF in 3, and EDAVF in 6 (C1-C2 level ratio =5:0, 2:1, 3:3). Patients with DAVF/RAVF in four lesions with intradural venous reflux underwent surgery, although an RAVF remained in one lesion after embolization/radiation. Since all six EDAVFs, two DAVFs, and one RAVF had neither feeder aneurysms nor significant symptoms, no treatment was provided; of these nine lesions, one DAVF and one RAVF remained unchanged, whereas six EDAVFs showed spontaneous obliteration within a year. Unfortunately, however, one DAVF bled before elective surgery. CONCLUSION: CCJAVFs have many variations of shunting site, angioarchitecture, and multiplicity, and they were frequently associated with coincidental vascular lesions. For symptomatic DAVF/RAVF lesions with intradural drainage, surgery is preferred, whereas asymptomatic EDAVFs without dangerous drainage may obliterate during their natural course.

Cellular therapy for myocardial ischemia using a temperature-responsive biodegradable injectable polymer system with adipose-derived stem cells.

Adipose-derived stem cell (AdSC) has been attracting attention as a convenient stem cell source. Not only AdSC can differentiate into various tissue cells, but it can also accelerate cell proliferation, anti-inflammation, and angiogenesis by secreting paracrine factors. Studies have demonstrated AdSC treatment of ischemic heart. However, an improvement in the remaining live AdSCs administered at the injected site while maintaining paracrine factor secretion is desired to achieve effective regenerative medicine. We previously reported the ABA-type tri-block copolymer of poly(ɛ-caprolactone-co-glycolic acid) and poly(ethylene glycol) (tri-PCG), exhibiting temperature-responsive sol-to-gel transition as biodegradable injectable polymer (IP) systems. Moreover, we recently reported that the biodegradable temperature-triggered chemically cross-linked gelation systems exhibited longer gel state durations using tri-PCG attaching acryloyl groups and a polythiol derivative. In this study, we explored this IP-mediated AdSC delivery system. We investigated the cell viability, mRNA expression, and cytokine secretion of AdSCs cultured in the physical or chemical IP hydrogels. Both of these IP hydrogels retained a certain number of viable cells, and RT-PCR and ELISA analyses revealed that mRNA expression and secretion of vascular endothelial growth factor of the AdSCs cultured in the chemical hydrogel were higher than the physical hydrogel. Moreover, AdSCs injected with the chemical hydrogel into ischemic heart model mice showed longer retention of the cells at the injected site and recovery from the ischemic condition. The results mean that the IP system is a promising candidate for a stem cell delivery system that exhibits the recovery of cardiac function for myocardial infarction treatment.

Emergent stenting after intravenous thrombolysis for isolated basilar artery dissection in a patient with acute ischemic stroke: a case report.

BACKGROUND: Isolated basilar artery dissection (IBAD) is a rare but important cause of ischemic stroke. Anti-thrombotic therapy is often used to treat IBAD-related ischemic stroke, but selected cases might need more aggressive treatment. There is no previous report of emergent stenting for IBAD-related ischemic stroke after intravenous thrombolysis. CASE PRESENTATION: A 53-year-old Japanese woman was admitted to our hospital with disturbance of consciousness, right hemiplegia, severe dysarthria, and total gaze paralysis. Brain magnetic resonance imaging revealed no ischemic lesion, but magnetic resonance angiography showed stenosis in the basilar artery. After initiation of intravenous thrombolysis, her neurological symptoms dramatically improved. Five hours later, however, her symptoms deteriorated again. Cerebral angiography showed IBAD. Emergent stenting was successfully performed. At 90 days after stroke onset, she had no significant disability, with a modified Rankin scale score of 1. CONCLUSIONS: Emergent stenting can be an effective treatment for patients with IBAD-related ischemic stroke who are resistant to IV-rtPA.

Trends in Incidence of Intracranial and Spinal Arteriovenous Shunts: Hospital-Based Surveillance in Okayama, Japan.

BACKGROUND AND PURPOSE: To date, the incidence of intracranial and spinal arteriovenous shunts has not been thoroughly investigated. We aimed to clarify recent trends in the rates of intracranial and spinal arteriovenous shunts in Japan. METHODS: We conducted multicenter hospital-based surveillance at 8 core hospitals in Okayama Prefecture between April 1, 2009 and March 31, 2019. Patients who lived in Okayama and were diagnosed with cerebral arteriovenous malformations, dural arteriovenous fistulas (DAVFs), or spinal arteriovenous shunts (SAVSs) were enrolled. The incidence and temporal trends of each disease were calculated. RESULTS: Among a total of 393 cranial and spinal arteriovenous shunts, 201 (51.1%) cases of DAVF, 155 (39.4%) cases of cerebral arteriovenous malformation, and 34 (8.7%) cases of SAVS were identified. The crude incidence rates between 2009 and 2019 were 2.040 per 100 000 person-years for all arteriovenous shunts, 0.805 for cerebral arteriovenous malformation, 1.044 for DAVF, and 0.177 for SAVS. The incidence of all types tended to increase over the decade, with a notable increase in incidence starting in 2012. Even after adjusting for population aging, the incidence of nonaggressive DAVF increased 6.0-fold while that of SAVS increased 4.4-fold from 2010 to 2018. CONCLUSIONS: In contrast to previous studies, we found that the incidence of DAVF is higher than that of cerebral arteriovenous malformation. Even after adjusting for population aging, all of the disease types tended to increase in incidence over the last decade, with an especially prominent increase in SAVSs and nonaggressive DAVFs. Various factors including population aging may affect an increase in DAVF and SAVS.

Improvement of Hemifacial Spasm after Stent-assisted Coil Embolization for Ipsilateral Vertebral Artery Dissecting Aneurysm.

Microvascular decompression (MVD) is the gold standard in the treatment of hemifacial spasm (HFS), and endovascular surgery has been described as a treatment only for aneurysm-induced HFS in several previous cases. We describe symptomatic HFS caused by a normal vertebral artery (VA) trunk adjacent to the ipsilateral dissecting VA aneurysm completely cured after stent-assisted coil embolization. A 52-year-old man presented with a 2-month history of gradually worsening left HFS. Magnetic resonance imaging (MRI) and cerebral angiography revealed a dissecting VA aneurysm on the left side. Based on the findings from preoperative MRI, not the aneurysmal dome itself, but the VA trunk just distal to the aneurysmal dome was considered likely to be compressing the root exit zone (REZ) of the facial nerve. Stent-assisted coil embolization was conducted for the VA aneurysm, and the stent was deployed to cover the wide neck of the aneurysm and offending zone of the VA trunk simultaneously. HFS started to show improvement just after the procedure and complete disappearance within 1 year. HFS was completely resolved by stenting of the offending artery. Stents may show efficacy for "intra-arterial decompression" by reducing pulsatility against the REZ of the facial nerve due to the thickness and rigidity of the stent metal and delayed endothelialization.

Effectiveness of Transvenous Aspiration Thrombectomy for Cerebral Venous Sinus Thrombosis: A Report of Three Cases.

Objective: We report three patients successfully treated by emergent transvenous thrombectomy for cerebral venous sinus thrombosis (CVST). Case Presentation: (Case 1) A 77-year-old man presented with vomiting, dizziness, and headache. CT revealed local subarachnoid hemorrhage (l-SAH), and angiography confirmed occlusion of the right transverse sigmoid sinus and superior sagittal sinus (SSS). Emergent transvenous aspiration thrombectomy using a Penumbra catheter (PC) resulted in effective reperfusion. (Case 2) A 60-year-old man developed disorientation, sensory aphasia, and right hemiparesis. MRI demonstrated extensive cerebral edema caused by venous congestion in both thalami, and angiography revealed poor opacification of the SSS, straight sinus, and bilateral transverse sinuses. Venous sinus flow was restored by catheter aspiration using a PC and topical infusion of urokinase (UK). (Case 3) A 19-year-old man developed a headache, numbness of the right upper limb, motor paralysis, and convulsions. CT revealed l-SAH and dense clot sign in the SSS. The SSS was poorly delineated on angiography. Thrombus aspiration using a PC and topical UK administration achieved partial recanalization. Conclusion: Transvenous aspiration thrombectomy using large lumen catheters for patients with CVST is effective and safe. In particular, this method may be a better option than anti-coagulation therapy alone for patients presenting with a severe neurological condition or intracranial hemorrhage.

Surgical Technique for Carotid Endarterectomy: Current Methods and Problems.

Over the last 60 years, many reports have investigated carotid endarterectomy (CEA) and techniques have thus changed and improved. In this paper, we review the recent literature regarding operational maneuvers for CEA and discuss future problems for CEA. Longitudinal skin incision is common, but the transverse incision has been reported to offer minimal invasiveness and better cosmetic effects for CEA. Most surgeons currently use microscopy for dissection of the artery and plaque. Although no monitoring technique during CEA has been proven superior, multiple monitors offer better sensitivity for predicting postoperative neurological deficit. To date, data are lacking regarding whether routine shunt or selective shunt is better. Individual surgeons thus need to select the method with which they are more comfortable. Many surgical techniques have been reported to obtain distal control of the internal carotid artery in patients with high cervical carotid bifurcation or high plaque, and minimally invasive techniques should be considered. Multiple studies have shown that patch angioplasty reduces the risks of stroke and restenosis compared with primary closure, but few surgeons in Japan have been performing patch angioplasty. Most surgeons thus experience only a small volume of CEAs in Japan, so training programs and development of in vivo training models are important.

Ramucirumab after prior sorafenib in patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein: Japanese subgroup analysis of the REACH-2 trial.

BACKGROUND: The global, randomized, phase 3 REACH-2 study (ClinicalTrials.gov identifier: NCT02435433) found significantly longer overall survival (OS) for second-line ramucirumab versus placebo (hazard ratio [HR]: 0.710, 95% confidence interval [CI] 0.531-0.949, P = 0.0199) in patients with advanced hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) ≥ 400 ng/mL. This prespecified subgroup analysis evaluated the efficacy and safety of ramucirumab in the Japanese patients enrolled in the study. METHODS: Patients with advanced HCC and AFP ≥ 400 ng/mL after first-line sorafenib were randomized 2:1 to ramucirumab (8 mg/kg intravenously) or placebo every 2 weeks. Hazard ratios for progression-free survival (PFS) and OS (primary endpoint of the overall study) were estimated using the stratified Cox regression model. We also pooled individual patient data from REACH-2 with data from REACH (NCT01140347) for patients with AFP ≥ 400 ng/mL. RESULTS: In the Japanese REACH-2 subpopulation, there were improvements for ramucirumab (n = 41) versus placebo (n = 18) in PFS (HR 0.282, 95% CI 0.144-0.553) and OS was numerically prolonged (HR 0.599, 95% CI 0.303-1.187), consistent with the significant benefit seen in the overall REACH-2 study population. In the ramucirumab and placebo arms, respectively, the objective response rate was 7.3% and 0%, and the disease control rate was 70.7% and 33.3%. The most frequently reported grade ≥ 3 treatment-emergent adverse event was hypertension (ramucirumab: 15%; placebo: 11%). CONCLUSIONS: Ramucirumab after prior sorafenib improved PFS and OS compared with placebo, with a manageable safety profile, in the Japanese REACH-2 subpopulation, consistent with the overall REACH-2 study results. Ramucirumab is the first agent to demonstrate clinical benefit for Japanese patients with HCC in the second-line setting.

Prestroke Conditions of Acute Ischemic Stroke Patients are Associated with Functional Outcome after Mechanical Thrombectomy.

BACKGROUND AND AIM: Mechanical thrombectomy was demonstrated to be useful for acute ischemic stroke. However, whether it is beneficial for patients with poor prestroke conditions, such as older adults and those with low activity of daily living, is unclear. METHODS: A total of 134 patients who underwent mechanical thrombectomy in our hospital between April 2015 and January 2019 were retrospectively evaluated. Good outcome was defined as modified Rankin scale score of 0-2 at 90 days after stroke onset. Several factors were analyzed to assess their effects on clinical outcomes. RESULTS: At 90 days after stroke onset, 37.3% (50 of 134) of patients had a good outcome. Prestroke modified Rankin scale score was independently associated with a good outcome (odds ratio .39, 95% confidence interval .22-.67, P < .001). In patients with prestroke modified Rankin scale score 0-1, 55.4% (46 of 83) had a good outcome, and no significant difference in prognosis was found between patients aged less than 80 years and those aged greater than or equal to 80 years (P = .64). More than half the patients with prestroke modified Rankin scale score greater than or equal to 2 were graded as modified Rankin scale score 5-6 at 90 days regardless of age, which was significantly higher than those with prestroke modified Rankin scale score 0-1 (P < .001). CONCLUSIONS: Patients with prestroke modified Rankin scale score 0-1 are expected to have a good prognosis after mechanical thrombectomy even if aged greater than or equal to 80 years. Patients with prestroke modified Rankin scale score greater than or equal to 2 might have an extremely poor prognosis, and we should be more careful in selecting candidates for mechanical thrombectomy.

Increased plasma plasmin-α2-plasmin inhibitor complex levels correlate with postoperative rebleeding after endoscopic surgery for spontaneous intracerebral hemorrhage.

BACKGROUND: Postoperative rebleeding (PR) is one of the most severe complications of endoscopic surgery, often performed to remove spontaneous intracerebral hemorrhage (sICH). However, the risk factors for PR remain unclear. OBJECTIVE: This study retrospectively investigated whether increased preoperative plasma plasmin-α2-plasmin inhibitor complex (PIC) levels, indicating activation of fibrinolysis, are associated with PR. METHODS: A total of 101 patients underwent endoscopic surgery to evacuate sICH at our institution from January 2010 to June 2019, and 79 patients who underwent examinations of plasma PIC levels at admission with available radiographical data were included. Correlations between PR and increased plasma PIC levels were retrospectively evaluated. RESULTS: PR occurred in eight patients (10.1%), and high PIC levels (≥ 4 or 6 µg/ml) were significantly associated with PR. The sensitivities employing high PIC levels of ≥ 4 µg/ml and ≥ 6 µg/ml were both 0.63, and the specificities using the same PIC levels were 0.86 and 0.92, respectively. Multivariable analyses showed that high plasma PIC levels of ≥ 4 µg/ml (odds ratio (OR), 12.77; 95% confidence interval (CI), 1.65-98.77; p = 0.02) or ≥ 6 µg/ml (OR, 18.33; 95% CI, 2.32-144.82; p = 0.006) were independent predictors of PR. CONCLUSIONS: This study found that increased plasma PIC levels were associated with PR following the endoscopic evacuation of sICHs, indicating that increased plasma PIC levels could be potentially used to predict PR. Further studies are needed to establish new surgical strategies and adjuvant treatments to improve surgical outcomes in patients with sICH prone to PR.

Factors Associated with Unsuccessful Recanalization in Mechanical Thrombectomy for Acute Ischemic Stroke.

INTRODUCTION: Mechanical thrombectomy (MT) for acute ischemic stroke has become a standard therapy, and the recanalization rate has significantly improved. However, some cases of unsuccessful recanalization still occur. We aimed to clarify patient factors associated with unsuccessful recanalization after MT for acute ischemic stroke. METHODS: This was a single-center, retrospective study of 119 consecutive patients with anterior circulation acute ischemic stroke who underwent MT at our hospital between April 2015 and March 2019. Successful recanalization after MT was defined as modified Treatment in Cerebral Ischemia (mTICI) grade 2b or 3, and unsuccessful recanalization was defined as mTICI grades 0-2a. Several factors were analyzed to assess their effect on recanalization rates. RESULTS: Successful recanalization was achieved in 88 patients (73.9%). The univariate analysis showed that female sex (38.6 vs. 67.7%, p = 0.007), a history of hypertension (53.4 vs. 83.9%, p = 0.003), and a longer time from groin puncture to recanalization (median 75 vs. 124 min, p < 0.001) were significantly associated with unsuccessful recanalization. The multivariate analysis confirmed that female sex (OR 3.18; 95% CI 1.12-9.02, p = 0.030), a history of hypertension (OR 4.84; 95% CI 1.32-17.8, p = 0.018), M2-3 occlusion (OR 4.26; 95% CI 1.36-13.3, p = 0.013), and the time from groin puncture to recanalization (per 10-min increase, OR 1.22; 95% CI 1.09-1.37, p < 0.001) were independently associated with unsuccessful recanalization. CONCLUSION: Female sex and a history of hypertension might be predictors of unsuccessful recanalization after MT for anterior circulation acute ischemic stroke. Further studies are needed to fully evaluate predictors of recanalization.

Does Noncontrast Computed Tomography Scan Predict Rebleeding After Endoscopic Surgery for Spontaneous Intracerebral Hemorrhage?

BACKGROUND: The relationship between noncontrast computed tomography (CT) markers, which predict the expansion of spontaneous intracerebral hemorrhage (sICH) under conservative treatment, and postoperative rebleeding (PR) after treatment by directly removing the sICH is unknown. This study investigated the relationship between noncontrast CT markers and PR in patients with sICH treated by endoscopic surgery. METHODS: The study population included 92 patients with available data who underwent endoscopic surgery for sICH at our institution from January 2010 to September 2018. The correlations between PR and preoperative noncontrast CT markers, including the blend sign, hypodensities, black hole sign, heterogeneous density, and island signs, were retrospectively evaluated. RESULTS: In 5 of the 18 patients (27.8%) with the blend sign, PR developed, whereas only 5 of 74 patients (6.8%) without the blend sign developed PR. In the univariate regression analyses, manifestation of hydrocephalus (odds ratio [OR], 8.75; 95% confidence interval [CI], 2.15-35.68; P = 0.002), presence of the blend sign (OR, 5.31; 95% CI, 1.34-20.97; P = 0.02), and insertion of external ventricular drainage (OR, 13.88; 95% CI, 3.22-59.77; P < 0.001) were significant risk factors. The other radiographic markers were not associated with PR. In a multivariate analysis, the presence of the blend sign (OR, 22.07; 95% CI, 2.18-223.60; P = 0.009) was the only independent predictor of PR. CONCLUSIONS: The blend sign is likely to be a strong predictor for PR in patients who undergo endoscopic surgery for sICH. To improve the prognosis of patients with sICH, further studies are needed to establish new treatment strategies and surgical procedures.

Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients.

BACKGROUND: The combination of pemetrexed and carboplatin is commonly used for the treatment of advanced non-squamous non-small cell lung cancer (NSCLC), mainly because it is comparatively effective and less toxic than other platinum-doublet therapies. Using the JMII (JACAL) study, we report the efficacy and safety of this treatment followed by pemetrexed maintenance in the elderly population (≥70 years of age). METHODS: The JMII study was a multicenter, post-marketing study that assessed the efficacy and safety of carboplatin (AUC6) and pemetrexed (500 mg/m2, given on Day 1 of a 21-day cycle, 4 cycles) followed by pemetrexed (500 mg/m2) maintenance in advanced non-squamous NSCLC patients (n = 109). Retrospective subgroup analyses were performed in elderly patients aged ≥70. RESULTS: The study includes younger (<70 years, n = 84) and elderly (≥70 years, n = 25) patients who received induction therapy. Median progression-free survival and overall survival from the start of the induction phase were 5.2 (95% CI: 3.5, 8.2) and 16.8 (95% CI: 10.3, NC) months for the elderly patients compared with 5.8 (95% CI: 4.3, 7.4) and 20.5 (95% CI: 16.7, NC) months for the younger patients, respectively. Grade 3/4 hematologic toxicities were more frequent in the elderly patients. Non-hematologic toxicities in the elderly patients were comparable to those in younger patients. Dose reduction was more common in the elderly (44% vs 23%), due to hematologic toxicities. CONCLUSIONS: There was no difference in efficacy (evaluated by progression-free survival) between elderly and younger patients. Although grade 3/4 hematologic toxicities were frequently observed in the elderly patients, they were easily managed with dose adjustment.

Silkworms suppress the release of green leaf volatiles by mulberry leaves with an enzyme from their spinnerets.

In response to herbivory, plants emit a blend of volatile organic compounds that includes green leaf volatiles (GLVs) and terpenoids. These volatiles are known to attract natural enemies of herbivores and are therefore considered to function as an indirect defense. Selection should favor herbivores that are able to suppress these volatile emissions, and thereby make themselves less conspicuous to natural enemies. We tested this possibility for silkworms, which were observed to leave secretions from their spinnerets while feeding on mulberry leaves. When we ablated the spinnerets of silkworms, no secretions were observed. Leaves infested by intact silkworms released smaller amounts of GLVs than leaves infested by ablated silkworms, indicating that the spinneret secretion suppressed GLV production. This difference in GLV emissions was also reflected in the behavioral response of Zenillia dolosa (Tachinidae), a parasitoid fly of silkworms. The flies laid fewer eggs when exposed to the volatiles from intact silkworm-infested leaves than when exposed to the volatiles from ablated silkworm-infested leaves. We identified a novel enzyme in the secretion from the spinneret that is responsible for the GLV suppression. The enzyme converted 13(S)-hydroperoxy-(9Z,11E,15Z)-octadecatrienoic acid, an intermediate in the biosynthetic pathway of GLVs, into its keto-derivative in a stereospecific manner. Taken together, this study shows that silkworms are able to feed on mulberry in a stealthy manner by suppressing GLV production with an enzyme in secretions of their spinnerets, which might be a countermeasure against induced indirect defense by mulberry plants.

Dose-finding study of the checkpoint kinase 1 inhibitor, prexasertib, in Japanese patients with advanced solid tumors.

Prexasertib is a novel inhibitor of checkpoint kinase 1. The primary objective of this study was to evaluate prexasertib tolerability in Japanese patients with advanced solid tumors. This nonrandomized single-arm open-label phase 1 study of prexasertib consisted of 2 dose levels, 80 mg/m2 and the global-recommended dose based on a US study of 105 mg/m2 , administered intravenously once every 14 days (n = 6 for each dose). Transition to the higher dose proceeded if the frequency of dose-limiting toxicity observed in cycle 1 was <33% at the lower dose. Safety measures, pharmacokinetics and antitumor activity were assessed. A total of 12 patients were treated. Two patients, one in each dose group, experienced dose-limiting toxicities of febrile neutropenia, one grade 4 and the other grade 3; both patients recovered and continued the study treatment. The grade 4 treatment-emergent adverse events related to study treatment were neutropenia (6 patients [50.0%]), leukopenia (4 patients [33.3%]), and 1 instance each (8.3%) of anemia, febrile neutropenia and thrombocytopenia. Neutropenia was generally transient and reversible; 11 patients (91.7%) required granulocyte colony-stimulating factor treatment during the study. There were no discontinuations due to adverse events or deaths. The prexasertib pharmacokinetics displayed dose-independent and time-independent behavior across both dose levels, similar to the profile observed in the US-based phase 1 study. Eight patients had a best overall response of stable disease. These data are consistent with the known safety profile for prexasertib and confirm its tolerability in Japanese patients with advanced solid tumors.