Technical and clinical outcomes of thrombectomy in patients with acute medium vessel occlusion and large vessel occlusion; sub-analyses of Japan Trevo registry.

BACKGROUND: Little is known about endovascular therapy (EVT) for patients with medium vessel occlusion (MeVO) and more work is needed to establish its efficacy and to understand hemorrhagic complications. METHODS: We analyzed the Japan Trevo Registry, which enrolled patients with acute stroke who underwent EVT using Trevo Retriever alone or in combination with an aspiration catheter. The primary outcome was effective reperfusion, and the secondary outcome was modified Rankin scale 0-2 at 90 days. Safety outcomes, including intracranial hemorrhage (ICH), were evaluated using a subgroup analyses focused on any ICH. RESULTS: Among 1041 registered patients, 1025 patients were analyzed. 253 patients had MeVOs, and the majority (89.3%) had middle cerebral artery segment 2 (M2). The median National Institutes of Health Stroke Scale scores at admission were 15 and 19 for the MeVO and LVO groups (p < 0.0001). The primary outcome was 88.9% in MeVO vs. 91.8% in LVO group: adjusted odds ratio (aOR) [95% confidence interval (CI)] 0.60 [0.35-1.03], p = 0.07, and the secondary outcome was 43.2% vs. 42.2%, and the aOR [95%CI] was 0.70 [0.48-1.002], p = 0.051. However, the incidence of any ICH was more prominent in MeVO than in LVO group (35.7% vs. 28.8%, aOR [95%CI] 1.54 [1.10-2.15], p = 0.01). In subgroup analyses, the incidences of any ICH in MeVO group were generally higher than those in LVO group. CONCLUSIONS: The effective reperfusion rate did not differ significantly between MeVO and LVO groups. Future development of devices and treatments for MeVO with fewer hemorrhagic complications is desirable.

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

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

Impact of atherosclerotic etiology on technical and clinical outcomes of mechanical thrombectomy with a stent retriever: subanalysis of the Japan Trevo Registry.

BACKGROUND: The safety and effectiveness of stent retriever use for patients with acute large vessel occlusion (LVO) due to intracranial atherosclerotic disease (ICAD) is not well established. We investigated the differences in clinical outcomes in patients with and without ICAD. METHODS: We analyzed the Japan Trevo Registry, a nationwide registry which enrolled patients with acute LVO who underwent endovascular therapy (EVT) using the Trevo retriever alone or in combination with an aspiration catheter. We compared the technical and clinical outcomes of EVT between the ICAD and No-ICAD groups. The primary outcome was effective reperfusion and the secondary outcome was modified Rankin scale (mRS) score 0-2 at 90 days. Safety outcomes were worsening of neurologic symptoms within 24 hours, any intracranial hemorrhage within 24 hours, vessel dissection/vessel perforation related to using the Trevo retriever and mortality at 90 days. RESULTS: A total of 835 patients (45 in the ICAD group and 790 in the No-ICAD group) were analyzed. In the ICAD group, more men (68.9% vs 50.8%, P=0.02) and a lower median National Institutes of Health Stroke Scale score at admission (11 vs 18, P<0.0001) were observed. The primary outcome was significantly more common in the No-ICAD group (92.5%) than in the ICAD group (80.0%) (adjusted odds ratio (aOR) 0.21, 95% CI 0.09 to 0.50). The proportion of patients with mRS score 0-2 at 90 days was significantly lower in the ICAD group (44.4% vs 42.4%, aOR 0.49, 95% CI 0.23 to 1.00, P=0.0496). Other secondary and safety outcomes were not significantly different between the two groups. CONCLUSIONS: Patients with LVO with ICAD had a lower rate of effective reperfusion than those with No-ICAD.

Short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE): a multicenter, open-label, randomized clinical trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after stent-assisted coil embolization (SACE) for cerebral aneurysm remains uncertain. This randomized trial of short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE) aimed to clarify whether long-term DAPT can reduce the occurrence of ischemic stroke in patients with cerebral aneurysms treated by SACE compared with short-term DAPT. METHODS: Patients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan. Patients were enrolled within 30 days after SACE and assigned in a 1:1 ratio to receive long-term (12 months) or short-term (3 months) DAPT with aspirin and clopidogrel. Randomization was performed centrally through a web-based system. The primary outcome was the time to ischemic stroke event during 3 to 12 months after SACE. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051180141). RESULTS: A total of 142 patients were recruited from November 4, 2016 to January 7, 2019. Among them, 65 and 68 patients assigned to the long- and short-term DAPT groups, respectively, were included in the full analysis set. Ischemic stroke occurred in no patients in the long-term DAPT group and in one patient in the short-term DAPT group. The incidence rate did not differ between the groups (0.0 vs 2.1/100 person-years; log rank test, P=0.33). CONCLUSIONS: In this multicenter randomized controlled trial, there was not a statistically significant difference in the rate of ischemic strokes between long- and short-term DAPT.

Mechanical Thrombectomy Using a Large Dual-Layer Stent Retriever for Near-Occlusion of the Common Carotid Bifurcation Caused by a Giant Free-Floating Thrombus.

Objective: We report a case of near-occlusion of the common carotid bifurcation caused by a giant free-floating thrombus (FFT) successfully treated with mechanical thrombectomy using a large dual-layer stent retriever. Case Presentation: A 51-year-old man presented to our hospital with dysarthria, right hemiparalysis, and paresthesia. MRI revealed an acute infarction of the left cortical watershed zone, and MRA revealed decreased signals in the left common carotid bifurcation. Carotid ultrasonography demonstrated a giant FFT in the left common carotid bifurcation. Angiography revealed a giant thrombus extending from the left common carotid artery (CCA) to the internal carotid artery (ICA) and the external carotid artery. As direct aspiration from both a balloon-guided catheter (BGC) and an aspiration catheter (AC) was ineffective, we deployed a large dual-layer stent retriever from the ICA to the CCA with an AC-connected aspiration pump and retrieved it under manual aspiration through the BGC. The giant thrombus was successfully removed, and complete recanalization was achieved without distal embolisms. Conclusion: Although there is no established treatment for giant thrombi in the carotid artery, mechanical thrombectomy using a large dual-layer stent retriever may be an effective treatment option.

Retrospective Observational Study of Patients With Subdural Hematoma Treated With Idarucizumab.

Use of anticoagulants is increasing with the aging of societies. The safe first-line drug is likely to be a direct oral anticoagulant (DOAC), but outcomes of treatment of traumatic brain injury (TBI) with anticoagulants are uncertain. Therefore, we examined the clinical effect of idarucizumab as reversal therapy in elderly patients with TBI who were treated with dabigatran. A retrospective multi-center observational study was performed in patients ≥65 years of age who developed acute traumatic subdural hematoma during treatment with dabigatran and underwent reversal therapy with idarucizumab. The items examined included patient background, neurological and imaging findings at arrival, course after admission, complications, and outcomes. A total of 23 patients were enrolled in the study. The patients had a mean age of 78.9 years. Cause of TBI was fall in 60.9% of the subjects. Mean Glasgow Coma Scale score at arrival was 8.7; anisocoria was present in 31.8% of cases. Exacerbation of consciousness was found in 30.4%, but only in 13.3% of subjects treated with idarucizumab before consciousness and imaging findings worsened. Dabigatran was discontinued in 81.8% of cases after hematoma development, with a mean withdrawal period of 12.1 days. The favorable outcome rate was 21.7%, and mortality was 39.1%. In multi-variate analysis, timing of idarucizumab administration was associated with a favorable outcome. There were ischemic complications in 3 cases (13.1%), and all three events occurred ≥7 days after administration of idarucizumab. These findings suggest that in cases that develop hematoma during treatment with dabigatran, it is important to administer idarucizumab early and restart dabigatran after conditions stabilize.

Japan Trevo Registry: Real-world Registry of Stent Retriever Alone or in Combined Therapy with Aspiration Catheter for Acute Ischemic Stroke in Japan.

Endovascular therapy (EVT) for real-world patients after extended time frames is associated with concerns about its efficacy and safety. We conducted a prospective registry at 77 centers between November 2019 and October 2020. The registry criteria included patients treated with Trevo Retriever alone or in combined therapy with an aspiration catheter. The primary outcome was effective reperfusion (thrombolysis in cerebral infarction grade ≥ 2b), the secondary outcome was a modified Rankin scale 0-2 at 90 days, and the safety outcomes were worsening of neurologic symptoms within 24 h postoperatively, intracranial hemorrhage (ICH) within 24 h after EVT and mortality. We also exlpored the difference between patients whose last known well time (LKWT) to a puncture was less than 6 h (0-6 h) and those whose LKWT was 6 h or more but less than 24 h (6-24 h). Among the 1041 patients registered, 1025 patients were analyzed. The mean age was 76.9 years, and 53.6% of the participants were males. The 6-24 h group was 206/998 (20.6%), the median National Institute of Health Stroke Scale (NIHSS) score at admission was 18, and the median Alberta Stroke Program Early CT score was 8. Combined technique as the first pass was used on 817 (79.7%) patients. The primary outcome was 934 (91.1%). The secondary outcome was 433/1021 (42.4%). Symptomatic ICH, any ICH, and mortality were 10/1019 (1.0%), 311/1019 (30.5%), and 75 (7.3%). In the subanalysis, the 6-24 h group was lower in NIHSS (median;18 vs 16), and the secondary outcome was not significantly different in the <6 h group. Even after treatment time expansion, this result was comparable to other Trevo-based trials and nationwide registries.

Carbon, nitrogen, and oxygen stable isotope ratios of striped dolphins and short-finned pilot whales stranded in Hokkaido, northern Japan, compared with those of other cetaceans stranded and hunted in Japan.

Strandings of striped dolphins (SD) and short-finned pilot whales (PW) in Hokkaido, northern Japan, are rare but have recently increased, probably due to global warming. We quantified δ13C, δ15N, and δ18O in muscles of SD (n = 7) and PW (n = 3) stranded in Hokkaido and compared these values with those in muscles (red meat products) of hunted SD and PW in three areas of central and southern Japan. δ18O in stranded SD, except for the calf, decreased with increasing body length (BL), whereas δ13C increased, with no BL-related changes in δ15N. The variability of δ18O (range of maximum and minimum) was larger in the stranded SD (7.5 ‰) than of the hunted SD in three areas (0.9, 1.9, and 1.4 ‰), whereas that of δ15N was smaller in the stranded SD than in the hunted SD. Similarly, the variability of δ18O was larger in the stranded PW in Hokkaido (3.3 ‰) than in the hunted PW in central Japan (1.4 ‰). The larger variability of δ18O and smaller variability of δ15N in stranded SD imply long-term sojourning in coastal waters and feeding on small amounts of limited prey species at low trophic levels before death.

Relation between duration of dual antiplatelet therapy and risk of ischemic stroke after stent-assisted treatment of cerebral aneurysm (DAPTS ACE-registry).

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in patients with cerebral aneurysm who undergo stent-assisted coil embolization (SACE) has not been established. We aimed to clarify the association between duration of DAPT and incidence of ischemic stroke in patients with cerebral aneurysm. METHODS: We registered patients with cerebral aneurysm who underwent SACE in 27 hospitals in Japan. Those treated with DAPT (aspirin and clopidogrel) were eligible for inclusion in a previously reported randomized control trial (RCT). Patients who were ineligible or refused to participate to the RCT were followed-up for 15 months after SACE as the non-RCT cohort. Our study examined both the RCT and non-RCT cohorts. The primary and secondary outcomes were ischemic stroke and hemorrhagic events. RESULTS: Among the 313 patients registered, 296 were included for analysis (of these, 136 were RCT patients and 160 were non-RCT patients). Patients who were treated with DAPT for more than 6 months (n=191) were classified as the long-term DAPT group. Those treated less than 6 months (n=105) were classified as the short-term group. The incidence of ischemic stroke did not significantly differ between the long-term group (2.5 per 100 person-years) and the short-term group (3.2 per 100 person-years); nor did incidence of hemorrhagic events (0.8 and 3.2 per 100 person-years, respectively). The period of DAPT was not significantly associated with incidence rates of ischemic stroke or hemorrhagic events. CONCLUSIONS: Duration of DAPT was not associated with the incidence of ischemic stroke in the first 15 months after SACE.

Identification of putative noncanonical driver mutations in patients with essential thrombocythemia.

Essential thrombocythemia (ET) cases without canonical JAK2, CALR, or MPL mutations, that is, triple-negative (TN) ET, have been found in 10%-20% of ET cases. Owing to the limited number of TN ET cases, its clinical significance remains unclear. This study evaluated TN ET's clinical characteristics and identified novel driver mutations. Among 119 patients with ET, 20 (16.8%) had no canonical JAK2/CALR/MPL mutations. Patients with TN ET tended to be younger and had lower white blood cell counts and lactate dehydrogenase values. We identified putative driver mutations in 7 (35%): MPL S204P, MPL L265F, JAK2 R683G, and JAK2 T875N were previously reported as candidate driver mutations in ET. Moreover, we identified a THPO splicing site mutation, MPL*636Wext*12, and MPL E237K. Four of the seven identified driver mutations were germline. Functional studies on MPL*636Wext*12 and MPL E237K revealed that they are gain-of-function mutants that increase MPL signaling and confer thrombopoietin hypersensitivity with very low efficiency. Patients with TN ET tended to be younger, although this was thought to be due to the inclusion of germline mutations, hereditary thrombocytosis. Accumulating the genetic and clinical characteristics of noncanonical mutations may help future clinical interventions in TN ET and hereditary thrombocytosis.

A decrease in newly diagnosed patients with adult T-cell leukemia/lymphoma in Kagoshima, a highly endemic area of HTLV-1 in southwestern Japan.

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type-I (HTLV-1). This study investigated whether the number of newly diagnosed patients with ATL is decreasing in the background of a declining number of individuals infected by HTLV-1 in Kagoshima, Japan, one of the most endemic areas of HTLV-1 in the world. We retrospectively analyzed the number of newly diagnosed patients with ATL between January 2001 and December 2021 in three major hospitals. The number of newly diagnosed patients with B-cell non-Hodgkin lymphoma (B-NHL) in the same period was examined as an internal control. One thousand eighteen and 2,029 patients with ATL and B-NHL were registered, respectively. The age-adjusted incidence of ATL steadily increased between 2001 and 2012, whereas that between 2013 and 2021 decreased. Despite the limitation of its retrospective nature, this is the first report indicating a decrease in ATL patients in Japan.

Profiles and determinants of dicofol, endosulfans, mirex, and toxaphenes in breast milk samples from 10 prefectures in Japan.

Human exposure to persistent organic pollutants (POPs) is reflected by POP concentrations in breast milk. Many studies of POPs in breast milk have been performed in Japan, but insufficient information is available about some legacy POPs (e.g., mirex and toxaphenes, included in the Stockholm Convention in 2001) and novel POPs (e.g., dicofol and endosulfans, included in the Stockholm Convention in 2019 and 2011, respectively). In this study, dicofol, endosulfan, mirex, and toxaphene concentrations in breast milk from 10 prefectures in Japan were determined. The samples were collected between 2005 and 2010, before Stockholm Convention restrictions on endosulfans and mirex were implemented. Common POPs (e.g., polychlorinated biphenyls) were also analyzed to allow the contamination statuses to be compared. The α-endosulfan and ß-endosulfan concentrations were 0.26-13 and 0.012-0.82 ng/g lipid, respectively. The toxaphene #26 and #50 concentrations were <0.08-5.6 and < 0.1-8.5 ng/g lipid, respectively. The dicofol concentrations were <0.01-4.8 ng/g lipid. The mirex concentrations were <0.2-3.5 ng/g lipid. The α- and ß-endosulfan concentrations on a lipid weight basis negatively correlated with the lipid contents of the milk samples (ρ = -0.65, p < 0.01 for α-endosulfan; ρ = -0.58, p < 0.01 for ß-endosulfan). The toxaphene concentrations positively correlated with the lipid contents. The mirex concentrations positively correlated with the maternal age but negatively correlated with the maternal body mass index. No correlations between the dicofol concentrations and the factors were found. Principal component analysis divided the data into four groups, (1) chlordanes, dichlorodiphenyltrichloroethanes and related compounds, hexachlorobenzene, hexachlorocyclohexanes, hexachloroethane, and polychlorinated biphenyls, (2) endosulfans, (3) dicofol, dieldrin, and toxaphenes, and (4) bromodiphenyl ether 47. This indicated that bromodiphenyl ether 47, dicofol, endosulfans, and toxaphenes have different exposure routes or different kinetics to the other legacy POPs.

Teratogenic Effects of Organohalogen Contaminants Extracted from Whale Bacon in a Whole-Rat-Embryo Culture System.

Marine foods can be contaminated with organochlorines and the risk to human beings who consume these foods needs to be evaluated. We examined the teratogenic effects of contaminants extracted from whale bacon on rat embryos using a whole-embryo culture system. Embryonic day 11.5 embryos were cultured for 48 h with organohalogens extracted from whale bacon at low (polychlorinated biphenyls (PCBs): 0.32 ppm, dichlorodiphenyltrichloroethanes (DDTs): 0.16 ppm, chlordanes (CHLs): 0.02 ppm) and high (PCBs: 2.15 ppm, DDTs: 1.99 ppm, CHLs: 0.20 ppm) doses. The levels of organohalogen compounds in cultured embryos were determined. The organochlorine contaminants extracted from whale products were readily transferred to the cultured rat embryos. The number of heartbeats, yolk sac circulation score, and embryonic body circulation score of embryos did not change during the culture period in either exposure group. Cultured embryos treated with the low-dose contaminated medium for 48 h showed abnormalities of the mandible, and craniofacial or forelimb hematomas with an incidence of 50%. All embryos treated with the high-dose medium showed craniofacial abnormalities and cleft lip, and limb abnormalities and hematomas. These results indicate that the organohalogen contaminants in whale bacon may be teratogenic in a dose-dependent manner. Further studies are necessary to determine the dose-effect relationship.

Use of Nonprescription and Prescription Drugs and Drug Information Sources among Breastfeeding Women in Japan: A Cross-Sectional Study.

Breastfeeding women may experience various health issues that require medication. This survey aimed to gain insights into the use of nonprescription and prescription drugs by breastfeeding women in Japan. A cross-sectional study involving women with children aged under two years was conducted in Fukuoka, Japan. Nonprescription drugs were used by 26% of participants in the breastfed-only group, 41% in the breastfed more than half the time group, 55% in the formula-fed more than half the time group, and 82% in the formula-fed-only group. We found that when breastfeeding rates decreased, the use of nonprescription drugs increased (p < 0.05, Cochran-Armitage test for trend). There were significant differences in the use of nonprescription cold medicines and oral analgesics between the formula-fed and breastfed groups, but a nonsignificant difference in prescription drugs use between the groups. These results indicated breastfeeding had a significant influence on use of nonprescription drugs, which was not observed with prescription drugs. Breastfeeding women commonly used the Internet to obtain information on both nonprescription and prescription drugs; however, this did not influence medication use.

Colonic Intramural Hematoma.

Colonic intramural hematoma is a rare condition and its endoscopic and radiological findings remain poorly described. An 82-year-old woman was hospitalized with a diagnosis of acute cerebral infarction. She immediately received anticoagulant therapy with argatroban for 1 week. With the appearance 4 days later of hematochezia, she was found to have severe anemia. Following insertion of the colonoscope, a large submucosal hematoma was shown to be present in the descending colon, with the mucosa shown to be necrotic and the residual mucosa around the hematoma shown to be yellowish. Computed tomography revealed a hyperdense mass in the descending colon. Laparoscopic colectomy was performed for the lesion diagnosed as intramural hematoma. Pathologically, it was a hematoma located in the subserosal layer involving full-thickness hemorrhage. To our knowledge, this report represents a valuable addition to the literature describing a case of colonic intramural hematoma whose diagnosis was effectively established by the combined use of CS and CT.

Simple and sensitive method for the determination of methylmercury in hair using thin-layer chromatography with thermal decomposition gold amalgamation atomic absorption spectrophotometry.

An improved method is described for the determination of methylmercury (MeHg) in human hair that is based on thin-layer chromatography and thermal decomposition gold amalgamation atomic absorption spectrophotometry. The dithizone extraction and application procedure of this technique were optimized, thus improving its sensitivity and robustness and enabling the use of less toxic solvents than other approaches. The limit of detection was 0.18 ng MeHg (as Hg), corresponding to 0.018 mg MeHg kg-1 of hair relative to a 10 mg sample. This method is appropriate for detecting MeHg in hair at the approximate reference dose level established by the United States Environmental Protection Agency.

Breast milk contribution to tissue mercury levels in rat pups examined by cross-fostering at birth.

The developing perinatal brain is vulnerable to methylmercury (MeHg) exposure. The contribution of breast milk to tissue MeHg levels in offspring is a significant public health concern because breast milk contains a certain amount of MeHg. Here, the contribution of MeHg transferred via breast milk to the Hg levels in the tissues of pups (Wistar rats) was investigated. Mated maternal rats were fed a MeHg (2 ppm)-supplemented or a control diet during pregnancy. Following parturition, male neonates from each group were cross-fostered between exposed or control dams, and they were further raised by dams fed a MeHg-supplemented diet or a control diet during lactation. Consequently, we evaluated three pup groups, which were raised by dams exposed to MeHg during pregnancy (P pups), lactation (L pups), or pregnancy and lactation (PL pups). Total mercury (THg) concentrations in the tissues of the offspring were measured at birth (postnatal day 0 [PD0]), during lactation (PD6, PD12, and PD19), and after weaning (PD29 and PD36). Blood and brain THg levels in the P and PL pups declined dramatically during lactation, however, there were no considerable differences between the two groups at PD6 and PD12. In contrast, blood and brain THg levels in the L pups increased slightly during lactation. The increase in the THg levels in the blood and brain of L pups at PD12 were approximately 3.3% and 1.5%, respectively, compared to the corresponding THg levels in the neonates in the P and PL groups. Our results suggest that if the MeHg exposure level during pregnancy is not high enough to cause neuronal development defects in the fetus, the exposure via breast milk is not a significant concern.

Identification of novel halogenated naturally occurring compounds in marine biota by high-resolution mass spectrometry and combined screening approaches.

Marine animals, plants or bacteria are a source of bioactive naturally-occurring halogenated compounds (NHCs) such as bromophenols (BPs), bromoanisoles (BAs) and hydroxylated or methoxylated analogues of polybrominated diphenyl ethers (HO-PBDEs, MeO-PBDEs) and bromobiphenyls (HO-BBs, MeO-BBs). This study applied a comprehensive screening approach using liquid chromatography high-resolution mass spectrometry and combining target, suspect and non-target screening with the aim to identify new hydroxylated NHCs which might be missed by commonly applied gas chromatographic methods. 24 alga samples, 4 sea sponge samples and 7 samples of other invertebrates were screened. Target screening was based on 19 available reference standards of BPs, (di)OH-BDEs and diOH-BBs and yielded seven unequivocally identified compounds. 6-OH-BDE47 was the most frequently detected compound with a detection frequency of 31%. Suspect screening yielded two additional compounds identified in alga samples as well as 17 and 8 compounds identified in sea sponge samples of Lamellodysidea sp. and Callyspongia sp., respectively. The suspect screening results presented here confirmed the findings of previous studies conducted on sea sponge samples of Lamellodysidea sp. and Callyspongia sp. Additionally, in Lamellodysidea sp. and Callyspongia sp. 13 and 4 newly identified NHCs are reported including heptabrominated diOH-BDE, monochlorinated pentabrominated diOH-BDE, hexabrominated OH-MeO-BDE and others. Non-target screening allowed the identification of 31 and 20 polyhalogenated compounds in Lamellodysidea sp. and Callyspongia sp. samples, respectively. Based on the obtained fragmentation spectra, polybrominated dihydroxylated diphenoxybenzenes (diOH-PBDPBs), such as hepta-, octa- and nonabrominated diOH-BDPBs, could be identified in both species. To our knowledge, this study is the first report on the environmental presence of OH-PBDPBs.

Comparison of Stent-Assisted Coiling for Unruptured Internal Carotid Artery Aneurysms Between LVIS or LVIS Jr. and Enterprise VRD: A Retrospective and Single-Center Analysis.

AIM: To compare the low-profile visualized intraluminal support (LVIS or LVIS Jr.) stent, which is a braided microstent, and Enterprise Vascular Reconstructive Device (VRD), which is fabricated using laser cutting technology, in the treatment of internal carotid artery aneurysms. MATERIAL AND METHODS: We investigated 49 unruptured aneurysm cases in which follow-up digital subtraction angiography had been performed. Results of the occlusion were divided into classes 1, 2, and 3 of the Raymond-Roy Occlusion Classification. Statistical significance was defined as p < 0.05. RESULTS: In the 49 aneurysm cases, we achieved class 1 in 23 (47%; LVIS or LVIS Jr., 7; Enterprise, 16; p=0.76), class 2 in 13 (27%; LVIS or LVIS Jr., 5; Enterprise, 8; p=0.74), and class 3 in 13 (27%; LVIS or LVIS Jr., 5; Enterprise, 8; p=0.74). Based on the follow-up imaging of the 49 aneurysms, we achieved class 1 in 32 cases (65%; LVIS or LVIS Jr., 16; Enterprise, 16; p < 0.01), class 2 in 7 (14%; LVIS or LVIS Jr., 0; Enterprise, 7; p < 0.01), and class 3 in 10 (20%; LVIS or LVIS Jr., 1; Enterprise, 9; p=0.13). CONCLUSION: Recently, the flow diversion effect of stents has garnered more attention compared to coil embolization. LVIS or LVIS Jr. exerts a higher flow diversion effect than other stents and may improve the Raymond-Roy Occlusion Classification. In the future, the role of stents in the treatment of aneurysms will become more important.

Plasma and red blood cells distribution of total mercury, inorganic mercury, and selenium in maternal and cord blood from a group of Japanese women.

Fetuses are a high-risk group for methylmercury (MeHg) exposure. The main objective of this study was to compare the characteristic profiles of total mercury (THg), inorganic mercury (IHg), MeHg, and selenium in plasma and red blood cells (RBCs) between maternal and cord blood at parturition collected from a group of Japanese women. Furthermore, correlations of THg in RBCs, which is a biomarker of MeHg, and THg in plasma, which is an IHg exposure biomarker, were examined in maternal and cord blood. Fifty-five pairs of maternal and cord blood samples obtained at parturition were collected from pregnant women in Fukuoka, Japan. THg in RBCs and plasma were significant correlated between maternal and cord blood. THg in RBCs was 13.9 ng/mL for cord and 9.16 ng/mL for maternal blood, with a cord:maternal RBCs ratio for THg of 1.58, suggesting that MeHg is actively transferred from the mother to the fetus via the placenta. THg in plasma showed a positive correlation with THg in RBCs for maternal and cord blood. This result suggests that measuring THg in plasma can overestimate the exposure level to IHg in fish-eating populations. The percentages of IHg in cord plasma and RBCs were 31% and 1.7%, respectively, and those in maternal plasma and RBCs were 46% and 5.9%, respectively. These results suggest that cord blood is rich in MeHg and can easily transfer to the fetal brain. Selenium in cord plasma was 67 ng/mL and that in maternal plasma was 97 ng/mL, with a cord:maternal plasma ratio for Se of 0.69, suggesting that the protective effects of Se against MeHg toxicity in fetuses may be weaker than those expected in adult mothers.