Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats.

Release of large amounts of adenosine triphosphate (ATP), a gliotransmitter, into the extracellular space by traumatic brain injury (TBI) is considered to activate the microglia followed by release of inflammatory cytokines resulting in excessive inflammatory response that induces secondary brain injury. The present study investigated whether antagonists of ATP receptors (P2X4 and/or P2X7) on microglia are beneficial for reducing the post-injury inflammatory response that leads to secondary injury, a prognostic aggravation factor of TBI. Adult male Sprague-Dawley rats were subjected to cortical contusion injury (CCI) and randomly assigned to injury and drug treatment conditions, as follows: i) No surgical intervention (naïve group); ii) dimethyl sulfoxide treatment after CCI (CCI-control group); iii) 5-BDBD (antagonist of P2X4 receptor) treatment after CCI (CCI-5-BDBD group); iv) CCI-AZ11645373 (antagonist of P2X7 receptor) treatment after CCI (CCI-AZ11645373 group); v) or 5-BDBD and AZ11645373 treatment after CCI (CCI-5-BDBD + AZ11645373 group). In the CCI-5-BDBD, CCI-AZ11645373, and CCI-5-BDBD + AZ11645373 groups, expression of activated microglia was suppressed in the ipsilateral cortex and hippocampus 3 days after the CCI. Western blotting with ionized calcium-binding adaptor molecule 1 antibody revealed that administration of CCI-5-BDBD and/or CCI-AZ11645373 suppressed expression of microglia and reduced expression of inflammatory cytokine mRNA 3 days after the CCI. Furthermore, the plus maze test, which reflects the spatial memory function and involves the hippocampal function, showed improvement 28 days after secondary injury to the hippocampus. These findings confirmed that blocking the P2X4 and P2X7 receptors, which are ATP receptors central in gliotransmission, suppresses microglial activation and subsequent cytokine expression after brain injury, and demonstrates the potential as an effective treatment for reducing secondary brain injury.

Factors associated with postsurgical muscle weakness in patients who undergo thoracic aortic surgery: a retrospective cohort study.

OBJECTIVE: Aortic surgery is often performed in elderly patients, and these patients have a high risk of postsurgical muscle weakness. To reinforce purposeful postsurgical rehabilitation, we aimed to investigate the factors associated with postsurgical muscle weakness in patients who underwent thoracic aortic surgery. METHODS: This retrospective cohort study analyzed data of consecutive patients who underwent elective thoracic aortic surgery with cardiopulmonary bypass, and whose knee extensor isometric muscle strength (KEIS) were measured pre- and postoperatively at University Hospital between January 2012 and December 2018. The primary outcome was percent change in KEIS (% change in KEIS). Multivariate linear regression analysis was used to identify independent risk factors for % change in KEIS. RESULTS: Overall, 218 patients were included. Multivariate linear regression analysis showed that mechanical ventilation time, days from initial sitting to 100 m walking, and the number of exercises in the rehabilitation room were associated with % change in KEIS. CONCLUSIONS: This study may serve as a reference to stratify patients at risk of postsurgical muscle weakness. The preventive or alternative interventions in patients undergoing thoracic aortic surgery will be assessed in future studies.

Glibenclamide reduces secondary brain injury in a SAH rat model by reducing brain swelling and modulating inflammatory response.

BACKGROUND: Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is a new therapeutic target. Sulfonylurea receptor 1 (SUR1) is expressed in nerve cells, glial cells, and vascular endothelial cells in EBI. SUR1 promotes intracellular inflow of Na and Ca ions, resulting in cell swelling and depolarization, and finally cell death. Glibenclamide reduced cerebral edema and mortality in a basic study of cerebral ischemia. However, the effects of glibenclamide on EBI have not been fully elucidated. This study examined the inhibitory effect of glibenclamide on EBI. METHODS: Rats were divided into the sham group, SAH-control group, and SAH-glibenclamide group. The water content of the brain was measured using the dry-wet method. In addition, the brain was divided into the cortex, putamen, and hippocampus, and expression of inflammatory cytokines was evaluated by the polymerase chain reaction method. In addition, microglia in the brain were evaluated immunohistologically. RESULTS: Water content of the brain was significantly decreased in the SAH-glibenclamide group compared to the SAH-control group. Interleukin-1beta (IL-1ß), tumor necrosis factor alpha (TNFα), and nuclear factor-kappa B significantly increased in the cerebral cortex after SAH. IL-1ß and TNFα in the cortex were significantly decreased in the SAH-glibenclamide group compared to the SAH-control group. Immunohistochemical staining confirmed that SAH causes extensive microglial activation in the brain, which was suppressed by glibenclamide. CONCLUSIONS: The present study showed that glibenclamide suppressed cerebral edema and activation of microglia and hypersecretion of inflammatory cytokines. Glibenclamide is a potential therapeutic method which may significantly improve the functional prognosis.

A Surgical Case for Pregnancy-Related Spontaneous Coronary Artery Dissection.

The efficacy of coronary artery bypass grafting for pregnancy-related spontaneous coronary artery dissection (SCAD) is controversial, as graft occlusion due to SCAD lesion healing has been reported. Only 24 grafts in 14 cases of coronary artery bypass grafting for SCAD have been reported: 8 of the 9 arterial grafts were occluded, but 9 of the 15 vein grafts were patent. We encountered a case of coronary artery bypass grafting with left internal thoracic artery to the left antero-descending branch due to pregnancy-related SCAD. The patient's graft revealed good patency immediately postoperatively but string signs 7 months later due to healing of SCAD lesions.

High-dose-infliximab-associated Cerebral Venous Sinus Thrombosis: A Case Report and Review of the Literature.

A 28-year-old woman experienced severe headache and right homonymous hemianopia after receiving high-dose infliximab for Crohn's disease. Computed tomography showed hemorrhagic infarction in the left temporal and parietal lobes. An angiogram revealed left transverse to sigmoid sinus occlusion and a stagnated Labbe vein. The patient was treated surgically and achieved a good outcome. Inflammatory bowel diseases are known to accompany venous and arterial thrombosis in 1-2% of cases. Recently, infliximab has been suggested to increase this possibility. A case of Crohn's disease presenting with cerebral sinus thrombosis in the remission period during long-term/high-dose use of infliximab is presented. In addition, infliximab-associated thrombosis cases were reviewed.

Venous hypertension caused by a meningioma involving the sigmoid sinus: case report.

BACKGROUND: Intracranial venous hypertension has been associated with a few cases of meningioma secondary to compression of the venous sinus. This is the rare case of small meningioma involving the sigmoid sinus leading to intracranial venous hypertension mimicking venous thrombosis. CASE PRESENTATION: A 39-year-old woman suffered visual dysfunction due to bilateral papilledema. Noncontrast head computed tomography (CT) showed no intracranial space-occupying lesions or hydrocephalus. Cerebrospinal fluid examination revealed high opening pressure. Various image inspections such as three-dimensional CT angiography, magnetic resonance imaging, and cerebral angiography demonstrated a small 2.5-cm lesion causing subtotal occlusion of the dominant right sigmoid sinus. No improvement of clinical manifestations was observed after medical treatment for 6 months, so right presigmoid craniectomy was performed. Operative findings revealed that the tumor was located predominantly involving the sigmoid sinus. The pathological diagnosis was fibrous meningioma. Postoperative fundoscopic examination showed improvement of bilateral papilledema. CONCLUSIONS: We treated a patient presenting with intracranial hypertension due to a small meningioma involving the sigmoid sinus. This unusual case suggests that early surgical strategies should be undertaken to relieve the sinus obstruction.

Do meteorological factors influence the occurrence of acute aortic dissection? A 10-year retrospective institutional study.

OBJECTIVE: This study aimed to clarify the relationship between meteorological factors and the occurrence of aortic dissection. METHODS: The study included 282 consecutive patients who were admitted to our institute with acute aortic dissection over a 10-year period. The local meteorological data over the same period were analyzed. RESULTS: On the days with occurrences of acute aortic dissection, there were significant differences in the following factors: the minimum and maximum temperature (p < 0.0001), difference in the minimum and maximum temperature from the 10-year average, atmospheric pressure (p < 0.0001), and difference in atmospheric pressure between the day of occurrence and the previous day. Cut-off values were determined by ROC curve analysis. Univariate analyses identified the following factors as significant predictors of the occurrence of acute aortic dissection: minimum temperature < 4.0 °C (OR 2.42, p < 0.0001), maximum temperature < 15.1 °C (OR 2.23, p < 0.0001), atmospheric pressure > 1008.9 hPa (OR 1.75, p < 0.0001), difference between the minimum temperature and 10-year average < 0.3 °C, difference between the maximum temperature and 10-year average < 0.44 °C; and the difference in atmospheric pressure between the day of occurrence and the previous day > 0.4 hPa. However, the differences of the minimum and maximum temperatures from the 10-year average were the only factors that remained significant in the multivariate analysis. The minimum (R2 = 0.3055) and maximum temperatures (R2 = 0.4151) were weakly and moderately correlated, respectively, with the occurrence of acute aortic dissection. CONCLUSION: Meteorological factors influenced the occurrence of acute aortic dissection. In particular, a minimum temperature of < 4 °C and maximum temperature difference from the 10-year average < 0.44 °C was identified as strong risk factors for the occurrence of acute aortic dissection.

Tectal Low-Grade Glioma with H3 K27M Mutation.

BACKGROUND: In the revised World Health Organization 2016 classification of central nervous system tumors, "diffuse midline glioma, H3 K27M-mutant" has been added as a new diagnostic entity. However, some confusion exists concerning this diagnostic entity because H3 K27M-mutant diffuse midline glioma is diagnosed with grade IV regardless of morphologic phenotype. Furthermore, the significance of H3 K27M mutation in tumors that aren't typical "diffuse midline glioma, H3 K27M-mutant," such as those with an unusual location and nontypical histology, remains unclear. CASE DESCRIPTION: To elucidate further such unusual tumors, we describe here a rare case of pediatric low-grade glioma located in the tectum, which was morphologically a pilocytic astrocytoma (PA) with genetically H3 K27M mutation but no microvascular proliferation, necrosis, mitoses, or other genetic alterations, insofar as we were able to observe. At the latest follow-up, 28 months after surgery, radiotherapy, and chemotherapy, the patient was found to be free from any neurologic deficits and MRI demonstrated that the tumor was stable without tumor regrowth. This case might be identified as "diffuse midline glioma, H3 K27M-mutant", grade IV, when applying only the current World Health Organization 2016 classification. In addition, we discuss the morphologically benign gliomas harboring the H3 K27M mutation based on the literature. CONCLUSIONS: We describe here a rare case and present a short literature review of circumscribed/nondiffuse gliomas, particularly in PA with H3 K27M mutation. However, the significance of H3 K27M mutation for PA remains unclear, so further studies and clinical data are needed to elucidate the biology and optimal treatment of such tumors.

Correction to: Extracorporeal membrane oxygenation support for postcardiotomy cardiogenic shock in adult patients: predictors of in­hospital mortality and failure to be weaned from extracorporeal membrane oxygenation.

In the original publication of the article, author group affiliation was published incorrectly.

Pituitary Apoplexy Accompanying Temporal Lobe Seizure as a Complication.

BACKGROUND: Pituitary apoplexy is an acute clinical syndrome caused by infarction and/or hemorrhage of pituitary adenoma, which typically presents with severe headache, visual deterioration, and endocrine abnormalities. However, temporal lobe seizure (and temporal lobe epilepsy) has not been viewed as a symptom of pituitary apoplexy in the literature. CASE DESCRIPTION: To elucidate further such a rare complication of temporal lobe seizure, we describe here the rare clinical manifestations of a 55-year-old previously healthy man with pituitary apoplexy harboring headache, combined palsies involving cranial nerves III to VI, endocrinologic disturbances, and temporal lobe seizure. In addition, we discuss the temporal lobe seizure (and temporal lobe epilepsy) associated with pituitary adenoma based on the literature. CONCLUSIONS: Although further accumulation of clinical data is needed, we would like to emphasize the importance of recognition of temporal lobe seizure caused by pituitary apoplexy, and to suggest that early surgery could be considered as an option in patients displaying such a rare complication.

Extracorporeal membrane oxygenation support for postcardiotomy cardiogenic shock in adult patients: predictors of in-hospital mortality and failure to be weaned from extracorporeal membrane oxygenation.

Postcardiotomy cardiogenic shock (PCCS) is a rare clinical entity associated with substantial morbidity and mortality. It is characterized by heart failure that results in an inability to be weaned from cardiopulmonary bypass (CPB). The aim of this study was to analyze the outcomes of extracorporeal membrane oxygenation (ECMO) in patients with PCCS and to identify predictors of in-hospital mortality and failure to be weaned from ECMO. From January 2002 to August 2016, 3248 patients underwent cardiac surgery in our hospital. Of these, 29 patients (0.89%) required ECMO because of an inability to be weaned from cardiopulmonary bypass. The median duration of ECMO support was 144 h (340-52 h) (range 17-818 h). Sixteen patients (55.2%) were weaned from ECMO, and 6 (20.7%) survived to hospital discharge. The multivariate analysis revealed that reoperation [odds ratio (OR): 13.667, 95% confidence interval (CI): 0.999-187.056, p = 0.05] and ECMO support duration > 130 h (OR: 17.688, 95% CI: 1.324-236.233, p = 0.03) were independent predictors of failure to be weaned from ECMO. Temporarily being weaned from CPB > 15 min (OR: 0.027, 95% CI: 0.001-0.586, p = 0.02) was found to be a protective factor. The multivariate analysis revealed that CPB time > 270 min (OR: 12.503, 95% CI: 1.058-147.718, p = 0.05) and ECMO support duration > 60 h (OR: 12.503, 95% CI: 1.058-147.718, p = 0.05) were independent predictors of in-hospital mortality. ECMO is an acceptable technique for treating PCCS in patients undergoing cardiac surgery. Our data suggest a reevaluation of therapeutic strategies after 60 h and again after 130 h of ECMO support.

[Frontal Lobe Signs Caused by Migration of a Burr Hole Cap into the Brain after Deep Brain Stimulation Surgery:A Case Report].

We report a rare complication in a patient with Parkinson's disease who underwent deep brain stimulation(DBS)surgery. The patient was a 60-year-old woman who presented with frontal lobe signs, including ataxic gait and memory disturbance, that were caused by the unexpected migration of a burr hole cap into the brain three to four months after surgery. The patient had no incidence of a head injury prior to development of symptoms. The patient underwent surgery to extract the migrated cap from the frontal lobe, and her symptoms improved several months after the operation. The cap serves to fix the DBS lead to the skull using an adjunctive burr hole ring. It was intraoperatively confirmed that only the cap detached from the ring, and no cap or ring defects were detected in a postoperative quality check by the manufacturer. We have previously utilized a burr hole ring and cap, which are packaged along with the DBS electrode, when employing the product made by Medtronic Inc. No previous report has described the cap packed in the official DBS kit to have migrated into the intracranial space. It seems unlikely that the cap migration into the intracranial space would occur without the cap and/or ring breaking through either traumatic injury or from manufacturing defects. It is important to consider the migration of a burr hole cap into the intracranial space in the absence of head injury as a possible device complication after DBS surgery.

The efficacy of immediate bridging thoracic endovascular aortic repair for ruptured infected thoracic aortic aneurysms.

Herein we describe four cases of ruptured infected thoracic aortic aneurysm. All patients underwent emergent thoracic endovascular aortic repair to stabilize hemodynamics. After controlling infection, stent graft removal and in situ reconstruction with radical debridement were performed in all but one case. All patients survived during the median 31-month follow-up period, and only one exhibited infection reactivation, which occurred 294 days after initial endoaortic repair. That particular patient underwent open repair. The current cases suggest that emergent bridging endovascular repair for ruptured infected thoracic aortic aneurysm is feasible and, after controlling infection, open repair should be performed as soon as possible.

Fungal endocarditis after transcatheter aortic valve replacement (TAVR): Case report and review of literature.

The reported number of transcatheter aortic valve replacement-associated infective endocarditis (TAVR-IE) cases has been increasing worldwide, but information about the incidence and clinical features of fungal TAVR-IE is quite limited. We present a patient who acquired TAVR-IE caused by Candida parapsilosis four month after TAVR, who was successfully treated redo-aortic valve replacement and prolonged antifungal therapy.

Strategy of Cardiovascular Surgery for Patients With Dementia as Evaluated by Mini-Mental State Examination.

BACKGROUND: The strategy for cardiovascular surgery in dementia patients is controversial, so we aimed to investigate whether preoperative dementia and its severity might affect the outcomes of cardiovascular surgery by evaluating with the Mini-Mental State Examination (MMSE). Methods and Results: The study group comprised 490 patients undergoing cardiovascular surgery. Their preoperative cognitive status was evaluated using the MMSE, and analysis was performed to compare the patients with MMSE score <24 (dementia group, n=51) or MMSE score 24-30 (non-dementia group, n=439). Furthermore, the effect of the severity of dementia was analyzed with a cut-off MMSE score of 19/20. Risk factors for surgical outcomes were explored using multivariate logistic regression analysis. Hospital mortality was 11.8% in the dementia group and 2.1% in the non-dementia group (P=0.002). Regarding the postoperative morbidities, the incidence of cerebrovascular disorder (P=0.001), pneumonia (P=0.039), delirium (P=0.004), and infection (P=0.006) was more frequent in dementia group. Among the patients with MMSE <20, hospital mortality was as high as 25%, and the rate of delirium was 58%. Multivariate logistic regression analysis revealed that MMSE score <24 (P=0.003), lower serum albumin (P=0.023) and aortic surgery (P=0.036) were independent risk factors for hospital death. CONCLUSIONS: Preoperative dementia affects the outcomes of cardiovascular surgery with regard to hospital death and delirium. The surgical indication for patients with MMSE <20 might be difficult, but surgery with an appropriate strategy should be considered for patients with MMSE <24.

Changes of Doublecortin-Immunoreactive Cells from the Acute Phase to Chronic Phase After Transient Global Brain Ischemia in Rat Cingulate Cortex.

Doublecortin (DCX)-immunoreactive (-ir) cells play important roles in adult cortical remodeling. We previously reported that DCX-ir cells decrease after transient global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. In the present study, we examined the changes of DCX-ir cells from the acute to the chronic phase after GBI in rats. Transient GBI was induced by a four-vessel occlusion model as described previously. Thirty-six rats were divided into six groups: day 7 after sham operation (Group Sham+A), day 7 after 3 min GBI (Group GBI3+A), day 7 after 10 min GBI (Group GBI10+A), day 90 after sham operation (Group Sham+C), day 90 after 3 min GBI (Group GBI3+C), and day 90 after 10 min GBI (Group GBI10+C). The numbers of DCX-ir cells per unit area (mm2) were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). A two-way factorial analysis of variance regarding the time of GBI (sham, GBI3, GBI10) or the period after GBI (day 7, day 90) was employed in each area. Regarding the time of GBI, there were significant differences in both the ACC and the RS (p < 0.001, respectively). Regarding the period after GBI, there was no significant difference in the ACC, whereas a significant difference was found in the RS (p = 0.005). In each area and in each phase, the numbers did not change in GBI3 (one-way ANOVA followed by a Tukey test) and decreased in GBI10 (p < 0.005). The numbers in the RS from the acute phase to chronic phase did not change in the sham and GBI3, and decreased in GBI10 (independent t-test, p < 0.001). However, histochemical staining with Fluoro-Jade B suggested that neuronal cell death did not occur in both the ACC and the RS in all groups. The present findings indicate that the cortical remodeling potential in the Cg decreases in the acute phase after GBI, and continues to decrease until the chronic phase.

Preoperative 6-Minute Walk Distance Is Associated With Postoperative Cognitive Dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a neurologic dysfunction that occurs after surgery. POCD persists for a long period, ranging from weeks to months, and affects a patient's quality of life. A 6-minute walk distance (6MWD) has been used to predict postoperative complications after several operations. The present study investigated whether there was an independent association of a low preoperative 6MWD with POCD in patients who underwent cardiac operations. METHODS: The study included 181 patients who underwent a cardiac operation. The 6MWD was performed prospectively on admission for the operation. POCD was defined as a decrease of 2 points or more in a patient's Mini-Mental State Examination score. POCD developed in 51 (28%) of these patients. Patients were categorized into a POCD or a non-POCD group, and the perioperative variables were compared between the groups. Multivariable logistic regression analysis was performed to identify risk factors for the development of POCD. RESULTS: The patients were a mean age of 71.4 years. The POCD group showed a significantly lower 6MWD (median, 400 m) than the non-POCD group (median, 450 m). The 6MWD, intensive care unit length of stay, age, and Mini-Mental State Examination score were identified as independent risk factors for POCD by multivariable analysis. The odds ratio for each increase of 50 m in the 6MWD was 0.807 for POCD. CONCLUSIONS: The 6MWD is useful in identifying patients with a higher chance of developing POCD after a cardiac operation.

The oral administration of clarithromycin prevents the progression and rupture of aortic aneurysm.

OBJECTIVE: The pathogenesis of aortic aneurysm (AA) is associated with chronic inflammation in the aortic wall with increased levels of matrix metalloproteinases (MMPs). Clarithromycin (CAM) has been reported to suppresses MMP activity. In this study, we investigated whether CAM could prevent the formation and rupture of AA. METHODS: Male apolipoprotein E-deficient mice (28-30 weeks of age) were infused with angiotensin II for 28 days. CAM (100 mg/kg/d) or saline (as a control) was administered orally to the mice every day (CAM group, n = 13; control group, n = 13). After the administration period, the aortic diameter, elastin content, macrophage infiltration, MMP levels, and levels of inflammatory cytokines, including nuclear factor κB (NF-κB), were measured. RESULTS: The aortic diameter was significantly suppressed in the CAM group (P < .001). No rupture death was observed in the CAM group in contrast to five deaths (38%) in the control group (P < .01). CAM significantly suppressed the degradation of aortic elastin (56.3% vs 16.5%; P < .001) and decreased the infiltration of inflammatory macrophages (0.05 vs 0.16; P < .01). Compared with the controls, the enzymatic activity of MMP-2 and MMP-9 was significantly reduced in the CAM group (MMP-2, 0.15 vs 0.56 [P < .01]; MMP-9, 0.12 vs 0.60 [P < .01]), and the levels of interleukin 1ß (346.6 vs 1066.0; P < .05), interleukin 6 (128.4 vs 346.2; P < .05), and phosphorylation of NF-κB were also decreased (0.3 vs 2.0; P < .01). CONCLUSIONS: CAM suppressed the progression and rupture of AA through the suppression of inflammatory macrophage infiltration, a reduction in MMP-2 and MMP-9 activity, and the inhibition of elastin degradation associated with the suppression of NF-κB phosphorylation.