Ghost twisting of the dual-layer flow-diverting stent.

The twisting phenomenon of the flow diverter stents rarely occurs, but it recently became relatively well-recognized. There have been few reports on single-layer flow diverters only. The Flow Redirection Endoluminal Device (FRED) (MicroVention, Tustin, California) has a unique design characterized by a braided dual-layer self-expanding stent. There have been no reports on the twisting phenomenon of FRED. This study reports two cases of acute in-stent blood flow disturbances after the deployment of FRED in a patient with intracranial aneurysms associated with "ghost twisting." In this phenomenon, the inner layer does not expand with the coning deformation, even though the outer layer is fully open. This was confirmed through high-resolution cone-beam computed tomography, but not conventional angiography. The two cases were successfully treated using balloon angioplasty and showed favorable outcomes. The structural issue of "ghost twisting" was a possible underlying factor for the ischemic complications associated with FRED deployment.

P2Y12 reaction units and ischemic and bleeding events after neuro-endovascular treatment.

BACKGROUND AND PURPOSE: To investigate the associations of perioperative P2Y12 reaction units (PRU) measured using VerifyNow with ischemic and bleeding events, and to determine the PRU threshold in the setting of elective neuro-endovascular treatment (EVT) for intracranial/extracranial vascular disease in patients taking aspirin and clopidogrel. METHODS: Of the patients undergoing elective neuro-EVT while taking aspirin and clopidogrel, those taking both antiplatelet agents for 7 days or more and whose PRU and aspirin reaction units (ARU) were measured were included. The primary and safety outcomes were defined as symptomatic ischemic and major bleeding events within 30 days after EVT. RESULTS: A total of 197 patients were available for the analyses. Higher PRU was associated with symptomatic ischemic events on multivariable logistic analysis (odds ratio per 10 increase 1.14 [95% confidence interval 1.03-1.27], p=0.011). Receiver operating characteristic curve analysis showed that PRU ≥212 was the threshold to predict symptomatic ischemic events (area under the curve=0.73; sensitivity, 62.5%; specificity, 82.0%). Lower PRU was also associated with major bleeding events (odds ratio per 10 increase 0.87 [0.78-0.96], p=0.004), and the threshold to predict major bleeding events was PRU ≤46 (area under the curve=0.76; sensitivity, 70.0%; specificity, 87.2%) CONCLUSIONS: The PRU value was associated with symptomatic ischemic and major bleeding events after elective neuro-EVT in patients taking aspirin and clopidogrel. PRU ≥212 and PRU ≤46 appeared to be the threshold values to predict symptomatic ischemic and major bleeding events, respectively.

Endovascular Treatment for Acute Ischemic Stroke After Video-Assisted Thoracoscopic Pulmonary Lobectomy in Patients With Lung Cancer: A Report of Four Cases and Literature Review.

BACKGROUND: Postoperative cerebral embolic stroke is a serious complication of pulmonary lobectomy, occurring in 1.1% of patients undergoing lobectomy through video-assisted thoracoscopic surgery (VATS). The mechanism of this complication is thought to be embolic stroke caused by thrombus formed due to stagnation in the pulmonary vein stump after VATS lobectomy. There have been few reports demonstrating the utility of endovascular treatment (EVT) for cerebral embolic stroke after VATS lobectomy. CASE DESCRIPTION: In our case series, cerebral embolic stroke occurred after VATS pulmonary lobectomy for lung cancer, including the left upper lobe in three cases and the right lobe in one. The median duration of ischemic stroke after VATS was 4.5 days (interquartile range, 2-9 days). The median time from stroke onset to puncture was 130 min. Successful recanalization was achieved in all cases, and two patients achieved favorable clinical outcomes (modified Rankin scale, 0-2). CONCLUSION: We report a case series of four patients who underwent EVT for acute embolic stroke after VATS lobectomy for lung cancer. EVT is considered a reasonable and feasible therapeutic option for this condition.

[Cerebellar Glioblastoma with Intrathecal Dissemination:A Report of Four Cases].

Primary cerebellar glioblastoma is a rare disease that accounts for 0.4-3.4% of glioblastoma multiforme(GBM)cases. The clinicopathological characteristics and prognosis of primary cerebellar GBM are not well understood due to its rarity and the lack of an established treatment strategy. To elucidate the prognostic factors and dissemination pattern, we retrospectively assessed four cases of cerebellar GBM that we treated between 2003 and 2013. All cases involved men, and the age range was 53 to 76 years(median 69.5 years);each patient underwent surgical removal and received adjuvant chemotherapy or radiotherapy. Every cerebellar GBM patient developed intrathecal dissemination at every stage of cerebellar GBM. Two patients had spinal metastases with tumor recurrence, and no patient had brain stem invasion. IDH1 mutation and MGMT expression were both negative in three cases. The median overall survival of cerebellar GBM patients was 13.8 years, and the median progression-free survival was 5.5 years, which is similar to that reported in previous reports-and similar in terms of results-for supratentorial GBM treated at the same time at our institution. In conclusion, the prognosis of cerebellar GBM appears to be similar to that of supratentorial GBM;however, the pattern of tumor progression, such as intrathecal dissemination, is different. Craniospinal irradiation on cerebellar GBM should be carefully considered with frequent follow-up by whole spine survey using MRI.

Influence of denture surface roughness and host factors on dental calculi formation on dentures: a cross-sectional study.

BACKGROUND: Dental calculi formation on dentures can worsen the oral cavity environment by complicating oral hygiene. However, few studies have investigated the effect of how patients use and manage their dentures, denture surface roughness, and host factors such as oral cavity dryness and saliva properties on denture cleanliness and denture dental calculi formation. Accordingly, we conducted the present survey to evaluate these factors to clarify the strength of the influence of each factor. METHODS: We enrolled 53 patients who had used dentures for at least 3 months and used a dental prosthesis that covered at least the six front teeth including the left and right mandibular canines. After staining the dentures, we divided the participants into a group that was positive for dental calculi (DCP group) and a group that was negative for dental calculi (DCN group). After removing all the stains, we evaluated the surface roughness of the dentures. A questionnaire was used to survey how the participants used and managed their dentures. Oral cavity dryness was evaluated, and resting saliva samples were collected to assess saliva properties. Correlations between the presence or absence of dental calculi and denture use and management were evaluated using a chi-square test. Correlations with denture surface roughness, oral cavity dryness, and saliva properties were evaluated using the Mann-Whitney U test. Correlations between the presence or absence of dental calculi and all factors were analyzed using multivariate analysis (quantification II). RESULTS: Surface roughness was significantly greater in the DCP group (p < 0.01), and the DCP group members wore their dentures during sleep significantly more often and used a denture cleaner when storing their dentures significantly less often (both p < 0.01). No significant differences were observed for oral cavity dryness or saliva properties. The multivariate analysis showed significant correlations of dental calculi formation with denture surface roughness and items related to denture use and management, but not for oral cavity dryness or saliva properties. CONCLUSIONS: Our findings indicate that dental calculi formation is influenced by how dentures are used and managed and by denture surface roughness, but not by oral cavity dryness and saliva properties.

A method for detecting rash and fever illness-associated viruses using multiplex reverse transcription polymerase chain reaction.

In this study, a new multiplex RT-PCR method for detecting various viral genes in patients with rash and fever illnesses (RFIs) was constructed. New primer sets were designed for detection of herpes simplex viruses 1 and 2 (HSV1 and 2), and Epstein-Barr virus (EBV). The newly designed and previously reported primer sets were used to detect 13 types of RFI-associated viruses by multiplex RT-PCR assay systems. Moreover, to eliminate non-specific PCR products, a double-stranded specific DNase was used to digest double-stranded DNA derived from the templates in clinical specimens. RFI-associated viruses were detected in 77.0% of the patients (97/126 cases) by the presented method, multiple viruses being identified in 27.8% of the described cases (35/126 cases). Detected viruses and clinical diagnoses were compatible in 32.5% of the patients (41/126 cases). Sensitivity limits for these viruses were estimated to be 101 -103 copies/assay. Furthermore, non-specific PCR products were eliminated by a double-stranded specific DNase with no influence on sensitivity. These results suggest that this method can detect various RFI-associated viruses in clinical specimens with high sensitivity and specificity.

Two-Step Effective Onyx Embolization from the Occipital Artery for the Treatment of Intracranial Dural Arteriovenous Fistula: A Technical Note.

AIM: To report our experience and the technique of two-step effective Onyx embolization from occipital artery (OA) for the obliteration of dural arteriovenous fistulas (DAVFs) with OA feeders. MATERIAL AND METHODS: The medical records of patients with intracranial DAVFs treated with trans-arterial embolization (TAE) using Onyx from the OA were retrospectively reviewed. RESULTS: Seven patients were included. The methods of Onyx injection from the OA were categorized as simple Onyx injection into the shunt, and two-step embolization. Two-step embolization involved the Onyx or coil embolization of the OA distal to the branching site of the feeders in the first step, and Onyx was injected toward the target shunt in the second step. Simple Onyx injection was performed in two cases; in both cases, the residual shunt remained. By contrast, the two-step embolization technique was performed in five cases, and in all those cases, sufficient embolization of the DAVFs was achieved. CONCLUSION: Prior embolization using Onyx or coil of the distal OA helped prevent Onyx from unexpected embolization through the subcutaneous branches that were not associated with the shunt, thereby leading to effective embolization. This new two-step embolization technique from the OA may improve the obliteration rate of DAVFs with OA feeders using TAE with Onyx.

Successful Retrieval of Filter Embolic Protection Device Fragment Trapped by a Carotid Stent: A Case Report.

Objective: Embolic protection devices are useful for preventing distal embolism during carotid artery stenting (CAS); however, complications have been reported. The successful removal of a filter fragment trapped at the distal edge of a carotid stent during the retrieval procedure is described. Case Presentation: CAS was performed for internal carotid artery stenosis in a patient in his 70s, and the carotid stent was successfully placed. During the retrieval procedure, the tip of the filter was trapped at the distal edge of the stent and detached from the filter. Using a snare kit, the filter tip was successfully retrieved, and no postoperative neurological symptoms occurred. Conclusion: The edge of a carotid stent can potentially trap devices. When trapping or fragmentation of a device is suspected, it is necessary to evaluate the situation and cause, and the device should be appropriately retrieved without using force.

Delayed hydrocephalus and visual field defect due to perianeurysmal inflammation after treating a large unruptured aneurysm with flow diverter and coil: A case report.

Flow diverter (FD) placement is increasingly used to treat large supraclinoid aneurysms. Here, we report a case of hydrocephalus following FD placement. One patient in her 60 s underwent FD placement combined with coil embolization. Within 1 month, the patient started to show visual field defects and symptoms of hydrocephalus, which worsened within another month. We report that hydrocephalus developed acutely, without high protein levels in the cerebrospinal fluid, and as a complication using a Surpass Streamline. Although the precise mechanisms are unclear, our report suggests a different mechanism for the development of hydrocephalus after FD placement combined with coil embolization.

Endovascular Treatment for Ruptured Proximal Anterior Cerebral Artery Dissecting Aneurysm: A Case Series.

Subarachnoid hemorrhage due to the A1 segment of an anterior cerebral artery dissecting aneurysm is rare. Therefore, a standard treatment has not been established. Though several case reports of direct surgery exist, there are few reports on endovascular treatment. This is the first study to describe five patients who underwent endovascular treatment for ruptured A1 dissecting aneurysms. Between January 2001 and December 2022 in our affiliated centers, five cases of SAH-onset A1 dissecting aneurysms were treated with endovascular treatment. We describe in detail two representative cases, briefly summarize the other three, and analyze their complications and outcomes. In the five cases, four were female. Four were in their 50s, and one was in her 80s. The WFNS grades were as follows: three were 2, one was 4, and one was 5. No re-ruptures or symptomatic complications were observed. The modified Rankin Scale scores at the time of discharge were as follows; one was 0, one was 1, two were 2, and one was 5. One in five patients needed retreatment after endovascular trapping because of recanalization. Endovascular treatment may be an effective and viable treatment option for ruptured A1 dissecting aneurysms. Further studies are needed to collect detailed data on complications and outcomes.

Impact of cancer history on long-term outcome after elective neuro-endovascular treatment in patients aged 80 years or older: A retrospective multicenter observational study.

AIM: Assessing the indication for elective neuro-endovascular treatment (EVT) in older patients requires consideration of the impact of systemic comorbidities on their overall reduced life expectancy. The objective of this study was to determine the long-term outcomes of elective neuro-EVT in patients aged ≥80 years, and to investigate the impact of pre-existing cancer on their long-term outcomes. METHODS: Of the patients enrolled in multicenter observational registry, those aged ≥80 years undergoing elective neuro-EVT between 2011 and 2020 were enrolled. A history of cancer was defined as a pre-existing solid or hematologic malignancy at the time of EVT. The primary outcome was time to death from elective neuro-EVT. RESULTS: Of the 6183 neuro-EVT cases implemented at 10 stroke centers, a total of 289 patients (median age, 82 years [interquartile range 81-84 years]) were analyzed. A total of 58 (20.1%) patients had a history of cancer. A total of 78 patients (27.0%) died during follow up. The 5-year survival rate of enrolled patients was 64.6%. Compared with patients without a history of cancer, those with a history of cancer showed significantly worse survival (log-rank test, P = 0.001). Multivariate Cox proportional hazards analysis showed history of cancer was an independent predictor of time to death from elective neuro-EVT (HR 1.74, 95% CI 1.01-3.00, P = 0.047). Cancer was the leading cause of death, accounting for 25.6% of all deaths. CONCLUSIONS: The present study showed that history of cancer has a significant impact on time to death from elective neuro-EVT in patients aged ≥80 years. Geriatr Gerontol Int 2024; 24: 211-217.

A Case of Dural Arteriovenous Fistula Following Cerebral Venous Sinus Thrombosis Associated with the COVID-19 Vaccine.

Objective: Cerebral venous sinus thrombosis (CVST) is one of the rare and severe complications of coronavirus disease 2019 (COVID-19) vaccines. CVST has also been reported to develop into dural arteriovenous fistula; however, there were no reports of dural arteriovenous fistula associated with COVID-19 vaccine-induced cerebral venous sinus thrombosis. Here, we describe a rare case of a transverse-sigmoid sinus dural arteriovenous fistula followed by CVST due to COVID-19 vaccination. Case Presentation: A 70-year-old patient presented with headache five days after receiving a second dose of COVID-19 vaccine. MRI showed a CVST in the superior sagittal sinus, left transverse sinus, and left sigmoid sinus. His headache improved after the administration of anticoagulant therapy. Six months later, a similar headache recurred, and cerebral angiography demonstrated a dural arteriovenous fistula in the left transverse sigmoid sinus and convexity dural arteriovenous fistulas in the left parietal cortex. The patient was treated twice with two sessions of transarterial embolization, and the shunts were completely occluded. His symptoms improved, and he was discharged with a modified Rankin Scale score of 0. Conclusion: Dural arteriovenous fistula can develop after CVST in association with COVID-19 vaccination.

Influence of Bilateral Cerebellar Infarction on Functional Outcome After Endovascular Treatment for Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: To measure the magnitude of the effect of the infarct location measured using the posterior circulation Alberta Stroke Program Early Computed Tomographic Score (pc-ASPECTS) on the functional outcome at 90 days in patients with basilar artery (BA) occlusion undergoing endovascular therapy (EVT). METHODS: Of the acute ischemic stroke patients undergoing EVT for acute posterior circulation large vessel occlusion enrolled in the multicenter observational registry from December 2013 to February 2021, patients with BA occlusion were included. A favorable outcome was defined as achieving a modified Rankin Scale score of 0-3 at 90 days. The effect of pc-ASPECTS including the distribution on favorable outcomes was evaluated. RESULTS: One hundred patients were analyzed. Fifty-one patients (51%) achieved favorable outcome. Patients achieving a favorable outcome were younger, had a lower National Institutes of Health Stroke Scale score before EVT, and had a higher pc-ASPECTS before EVT than those not achieving a favorable outcome. Multivariable logistic analysis showed a significant association between higher pc-ASPECTS and a favorable outcome (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.02-1.52; P = 0.028). Considering the infarct location, bilateral cerebellar infarction was significantly associated with a lower frequency of favorable outcomes than those without cerebellar infarction (OR 0.16; 95% CI 0.04-0.51; P = 0.002). CONCLUSIONS: A higher pc-ASPECTS before EVT could be a predictor of a favorable outcome after EVT for BA occlusion. In particular, the presence of bilateral cerebellar infarction before EVT was significantly associated with a lower likelihood of a favorable outcome.

Imaging predictors of clinical outcomes after endovascular treatment in MRI-selected patients with acute basilar artery occlusion.

PURPOSE: We aimed to investigate the impact of baseline infarct area and collateral status (CS), which are imaging predictors of clinical outcome following stroke, after endovascular treatment (EVT) in MRI-selected patients with acute basilar artery occlusion (BAO). METHODS: Patients with acute BAO who underwent EVT within 24 h after stroke from December 2013 to February 2021 were included in this retrospective, multicenter, observational study. The baseline infarct area was evaluated by the posterior circulation of Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) using diffuse-weighted imaging (DWI), and CS was assessed by measuring the computed tomography angiography of the basilar artery (BATMAN) score and the posterior circulation collateral score (PC-CS) using magnetic resonance angiography (MRA). A Good outcome was defined as a modified Rankin scale score ≤ 3 at 3 months. For each imaging predictor, a multivariate logistic regression analysis was performed to evaluate its impact on good outcomes. RESULTS: A total of 86 patients were analyzed, and 37 (43.0%) had a good outcome. The latter showed significantly higher pc-ASPECTS than those without good outcomes. In multivariate analyses, a pc-ASPECTS ≥ 7 was significantly associated with good outcomes (OR, 2.98 [95% CI, 1.10-8.13], P = 0.032), while PC-CS ≥ 4 (OR, 2.49 [95% CI, 0.92-6.74], P = 0.073) and BATMAN score ≥ 5 (OR, 1.51 [95% CI, 0.58-3.98], P = 0.401) were not. CONCLUSIONS: In MRI-selected patients with acute BAO, pc-ASPECTS on DWI was an independent predictor of clinical outcomes after EVT, while the MRA-based CS assessments were not.

Correlation between the CT Perfusion Parameter Values and Response to Recanalization in Patients with Acute Ischemic Stroke.

Objective: CT perfusion (CTP) provides various hemodynamic parameters. However, it is unclear which CTP parameters are useful in predicting clinical outcome in patients with acute ischemic stroke (AIS). Methods: Between February 2019 and June 2021, patients with anterior circulation large-vessel occlusion who achieved successful recanalization within 8 hours after stroke onset were included. The relative CTP parameter values analyzed by the reformulated singular value decomposition (SVD) method in the affected middle cerebral artery territories compared to those in the unaffected side were calculated. In addition, the ischemic core volume (ICV) was evaluated using a Bayesian Vitrea. The final infarct volume (FIV) was assessed by 24-hour MRI. The correlation between these CTP-derived values and clinical outcome was assessed. Results: Forty-two patients were analyzed. Among the CTP-related parameters, the ICV, relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) showed a strong correlation with the FIV (ρ = 0.74, p <0.0001; ρ = -0.67, p <0.0001; and ρ = -0.66, p <0.0001, respectively). In multivariate analysis, rCBV, rMTT, and ICV were significantly associated with good functional outcome, which was defined as a modified Rankin Scale score ≤2 (OR, 6.87 [95% CI, 1.20-39.30], p = 0.0303; OR, 11.27 [95% CI, 0.97-130.94], p = 0.0269; and OR, 36.22 [95% CI, 2.78-471.18], p = 0.0061, respectively). Conclusion: Among the CTP parameters analyzed by the SVD deconvolution algorithms, rCBV and rMTT could be useful imaging predictors of response to recanalization in patients with AIS, and the performances of these variables were similar to that of the ICV calculated by the Bayesian Vitrea.

Novel acid trehalase belonging to glycoside hydrolase family 37 from Pleurotus sp.: cloning, expression and characterization.

The N-terminal amino acid sequence of the Pleurotus sp. 90 kDa protein was in good agreement with the corresponding sequence of the glycoside hydrolase (GH) family 37 protein (trehalase) from P. ostreatus PC 15 v2.0. The length of the Pleurotus sp. trehalase gene was 2247 bp, encoding a protein of 749 amino acids with a predicted molecular mass of 81.2 kDa. The molecular mass of the recombinant enzyme was estimated to be about 117 kDa by SDS-PAGE. We found that the recombinant enzyme comprised an N-glycosylated sugar chain and that its optimum pH and temperature were 4.5 and 40 ºC, respectively. Moreover, this enzyme exhibited high activity against trehalose exclusively. We found that the enzyme is novel acid trehalase belonging to GH family 37.

Initial Management of Patients with Suspected Stroke in the SARS-CoV-2 Era: Effects on the Door-to-Picture Time.

Objective: To examine the effectiveness of a newly developed emergency room (ER) protocol to treat patients with stroke and control the spread of SARS-CoV-2 by evaluating the door-to-picture time. Methods: We retrospectively enrolled 126 patients who were transported to our ER by ambulance with suspected stroke between April 15 and October 31, 2020 (study group). A risk judgment system named the COVID level was introduced to classify the risk of infection as follows: level 0, no infection; I, infection unlikely; II, possible; III, probable; and IV, definite. Patients with COVID levels 0, I, or II and a Glasgow Coma Scale (GCS) score >10 were placed in a normal ER (nER) without atmospheric pressure control; the medical staff wore standard personal protective equipment (PPE) in such cases. Patients with COVID level II, III, or IV, and a GCS score of ≤10 were assigned to the negative pressure ER (NPER); the medical staff wore enhanced PPE for these cases. The validity of the protocol was assessed. The door-to-picture time of the study group was compared with that of 114 control patients who were transported with suspected stroke during the same period in 2019 (control group). The difference in the time for CT and MRI between the two groups was also compared. In the study group, the time spent in the nER and NPER was evaluated. Results: In all, 118 patients (93.7%) were classified as level I, 6 (4.8%) as level II, and 2 (1.6%) as level III. Only five patients (4.0%) were treated with NPER. Polymerase chain reaction tests were performed on 118 out of 126 patients (93.7%) and were negative. No significant differences were observed in age, sex, neurological severity, modalities of diagnostic imaging, and diagnosis compared with the control group. The median door-to-picture time was 18 (11-27.8) min in the study group and 15 (10-25) min in the control group (p = 0.08). No delay was found on CT (15 [10-21] vs. 14 [9-21] min, p = 0.24). In contrast, there was an 8-min delay for MRI (30 [21.8-50] vs. 22 [14-30] min, p = 0.01). The median door-to-picture time was 29 min longer in patients treated with NPER than in those treated with nER, although the difference was not significant due to the small number of patients (47 [27-57] vs. 18 [11-26] min, p = 0.07). Conclusion: Our protocol could optimize the use of medical resources with only a 3-min delay in the door-to-picture time in an area without explosive outbreak. Unfortunately, the effectiveness of the protocol in preventing infection could not be verified because of the low incidence of COVID-19. When developing and modifying an institutional protocol, recognizing the outbreak status surrounding each institution is important.

Increased Lung Uric Acid Deteriorates Pulmonary Arterial Hypertension.

Background Recent studies have demonstrated that uric acid (UA) enhances arginase activity, resulting in decreased NO in endothelial cells. However, the role of lung UA in pulmonary arterial hypertension (PAH) remains uncertain. We hypothesized that increased lung UA level contributes to the progression of PAH. Methods and Results In cultured human pulmonary arterial endothelial cells, voltage-driven urate transporter 1 (URATv1) gene expression was detected, and treatment with UA increased arginase activity. In perfused lung preparations of VEGF receptor blocker (SU5416)/hypoxia/normoxia-induced PAH model rats, addition of UA induced a greater pressure response than that seen in the control and decreased lung cGMP level. UA-induced pressor responses were abolished by benzbromarone, a UA transporter inhibitor, or L-norvaline, an arginase inhibitor. In PAH model rats, induction of hyperuricemia by administering 2% oxonic acid significantly increased lung UA level and induced greater elevation of right ventricular systolic pressure with exacerbation of occlusive neointimal lesions in small pulmonary arteries, compared with nonhyperuricemic PAH rats. Administration of benzbromarone to hyperuricemic PAH rats significantly reduced lung UA levels without changing XOR (xanthine oxidoreductase) activity, and attenuated right ventricular systolic pressure increase and occlusive lesion development. Topiroxostat, a XOR inhibitor, significantly reduced lung XOR activity in PAH rats, with no effects on increase in right ventricular systolic pressure, arterial elastance, and occlusive lesions. XOR-knockout had no effects on right ventricular systolic pressure increase and arteriolar muscularization in hypoxia-exposed mice. Conclusions Increased lung UA per se deteriorated PAH, whereas XOR had little impact. The mechanism of increased lung UA may be a novel therapeutic target for PAH complicated with hyperuricemia.

Chronic Inhibition of Toll-Like Receptor 9 Ameliorates Pulmonary Hypertension in Rats.

Background Recent accumulating evidence suggests that toll-like receptor 9 (TLR9) is involved in the pathogenesis of cardiovascular diseases. However, its role in pulmonary hypertension remains uncertain. We hypothesized that TLR9 is involved in the development of pulmonary hypertension. Methods and Results A rat model of monocrotaline-induced pulmonary hypertension was used to investigate the effects of TLR9 on hemodynamic parameters, vascular remodeling, and survival. Monocrotaline-exposed rats significantly showed increases in plasma levels of mitochondrial DNA markers, which are recognized by TLR9, TLR9 activation in the lung, and interleukin-6 mRNA level in the lung on day 14 after monocrotaline injection. Meanwhile, monocrotaline-exposed rats showed elevated right ventricular systolic pressure, total pulmonary vascular resistance index and vascular remodeling, together with macrophage accumulation on day 21. In the preventive protocol, administration (days -3 to 21 after monocrotaline injection) of selective (E6446) or nonselective TLR9 inhibitor (chloroquine) significantly ameliorated the elevations of right ventricular systolic pressure and total pulmonary vascular resistance index as well as vascular remodeling and macrophage accumulation on day 21. These inhibitors also significantly reduced NF-κB activation and interleukin-6 mRNA levels to a similar extent. In the short-term reversal protocol, E646 treatment (days 14-17 after monocrotaline injection) almost normalized NF-κB activation and interleukin-6 mRNA level, and reduced macrophage accumulation. In the prolonged reversal protocol, E6446 treatment (days 14-24 after monocrotaline injection) reversed total pulmonary vascular resistance index and vascular remodeling, and improved survival in monocrotaline-exposed rats. Conclusions TLR9 is involved in the development of pulmonary hypertension concomitant via activation of the NF-κB‒IL-6 pathway. Inhibition of TLR9 may be a novel therapeutic strategy for pulmonary hypertension.

[Medical care support intervention to the patient and family who has chosen a terminal care at home - an influence of satisfactory experience on the culture of terminal care].

The National Center for Geriatrics and Gerontology in Japan implemented a home medical care support system for aged patients in April 2009. In this study, we report a case of terminal care system where a medical care intervention was carried out by a close coordination of visiting nurses and other staffs with a "at-home terminal care" brochure on hand, and we discussed how this system was brought forward satisfactory and how it affected this culture.