Prediction for the prognosis of diffuse axonal injury using automated pupillometry.

OBJECTIVE: Previous studies have reported various predictive indicators of diffuse axonal injury (DAI), but no consensus has not been reached. Although the efficiency of automated pupillometry in patients with consciousness disorder has been widely reported, there are few reports of its use in patients with DAI. This study aimed to investigate the significance of pupillary findings in predicting the prognosis of DAI. PATIENTS AND METHODS: We included patients admitted to our center with a diagnosis of DAI from June 1, 2021 to June 30, 2022. Pupillary findings in both eyes were quantitatively measured by automated pupillometry every 2 hours after admission. We statistically examined the correlations between automated pupillometry parameters, the patients' characteristics, and outcomes such as the Glasgow Outcome Scale Extended (GOSE) after 6 months from injury, the time to follow command, and so on. RESULTS: Among 22 patients included in this study, five had oculomotor nerve palsy. Oculomotor nerve palsy was correlated with all outcomes, whereas Marshall computed tomography (CT) classification, Injury severity score (ISS) and DAI grade were correlated with few outcomes. Some of the automated pupillometry parameters were significantly correlated with GOSE at 6 months after injury, and many during the first 24 hours of measurement were correlated with the time to follow command. Most of these results were not affected by adjustment using sedation period, ISS or Marshall CT classification. A subgroup analysis of patients without oculomotor nerve palsy revealed that many of the automated pupillometry parameters during the first 24 hours of measurement were significantly correlated with most of the outcomes. The cutoff values that differentiated a good prognosis (GOSE 5-8) from a poor prognosis (GOSE 1-4) were constriction velocity (CV) 1.43 (AUC = 0.81(0.62-1), p = 0.037) and maximum constriction velocity (MCV) 2.345 (AUC = 0.78 (0.58-0.98), p = 0.04). The cutoff values that differentiated the time to follow command into within 7 days and over 8 days were percentage of constriction 8 (AUC = 0.89 (0.68-1), p = 0.011), CV 0.63 (AUC = 0.92 (0.78-1), p = 0.013), MCV 0.855 (AUC = 0.9 (0.74-1), p = 0.017) and average dilation velocity 0.175 (AUC = 0.95 (0.86-1), p = 0.018). CONCLUSIONS: The present results indicate that pupillary findings in DAI are a strong predictive indicator of the prognosis, and that quantitative measurement of them using automated pupillometry could facilitate enhanced prediction for the prognosis of DAI.

Massive Hemorrhage Associated With Upper Cervical Vertebral Fracture Treated Successfully With Transcatheter Arterial Embolization: A Case Report.

Blunt vertebral artery injuries (BVAI) associated with cervical spine fractures are often problematic due to symptoms of occlusion. Denver grade V cases, in which the vertebral artery is transected, are rare but often fatal, and treatment has rarely been reported. We encountered a case of hemorrhagic shock due to an injury to a branch of the vertebral artery associated with an upper cervical spine fracture. Transcatheter arterial embolization was performed successfully to achieve hemostasis, requiring superselective arterial embolization to preserve the main trunk of the vertebral artery. It is important to be aware that vascular injuries to the branch vessels as well as the main trunk can cause complications.

Caffeine poisoning successfully treated by venoarterial extracorporeal membrane oxygenation and emergency hemodialysis.

BACKGROUND: Caffeine overdose can cause life-threatening circulatory failure, neurological abnormalities, and ventricular fibrillation. We report the case of a patient with caffeine poisoning who was successfully treated with early hemodialysis and venoarterial extracorporeal membrane oxygenation. CASE PRESENTATION: A 43-year-old man who had ingested pills containing 20 g caffeine was transported to the hospital 100 min after ingestion. Hemodynamic collapse and refractory arrhythmia were most likely the potential complications. The patient developed ventricular fibrillation when placed in the left lateral decubitus position. Return of spontaneous circulation with defibrillation and introduction of venoarterial extracorporeal membrane oxygenation were followed by emergency dialysis, which led to rapid improvement in the clinical findings. CONCLUSION: Acute caffeine poisoning in a patient who developed an arrhythmia was successfully treated using an indwelling arterial and venous sheath followed by venoarterial extracorporeal membrane oxygenation.

Aggressive Intraoperative Cisternal Clot Removal After Clipping Aneurismal Subarachnoid Hemorrhage in Elderly Patients.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) in the elderly often has a poor prognosis even after surgical treatment in the acute phase. Additionally, subarachnoid clots are the strongest predictors of cerebral vasospasm and tend to be thicker and heavier due to cerebral atrophy. We aimed to compare the conventional surgical treatment in such patients and identify the independent predictors of a favorable outcome after aggressive surgical clot removal. METHODS: We included 40 patients with aSAH aged 70 or older. Each patient underwent aneurysmal clipping. We used the modified Rankin Scale to assess the primary outcome of neurologic status at discharge. We performed univariate analysis using the following factors: sex, age, neurologic, and general medical condition, radiographic data, aneurysm location, treatment approach, and timing of the aneurysm surgery. We divided the patients into irrigation and nonirrigation groups. We focused mainly on subarachnoid clots and analyzed them semiquantitatively using computed tomography. RESULTS: Clot removal was significantly greater in the irrigation group (n = 21) than in the nonirrigation group (n = 19). The period of intrathecal drainage was significantly shorter in the irrigation group (P = 0.002). The rate of occurrence of new low-density areas on CT scans was higher in the nonirrigation group. Outcomes were better in the irrigation group (P = 0.010). CONCLUSIONS: In elderly patients with aSAH in the acute phase, aggressive surgical clot removal after clipping showed favorable outcomes by facilitating early out-of-bed mobilization.

Impact of functional ABCG2 polymorphisms on the adverse effects of gefitinib in Japanese patients with non-small-cell lung cancer.

PURPOSE: ABCG2 is a half-size ATP-binding cassette transporter implicated in cellular gefitinib transport. Reportedly, the c.421C > A ABCG2 gene polymorphism was associated with gefitinib-induced diarrhea in Caucasian patients with non-small-cell lung cancer. Since c.421C > A ABCG2, resulting in p.Q141K substitution, is more prevalent in Asian populations, the putative relationship between gefitinib-induced adverse effects and this functional polymorphism was investigated in Japanese patients. c.376C > T, resulting in truncated, non-functional ABCG2, was also investigated. METHODS: ABCG2 gene polymorphisms were evaluated in 75 patients with non-small-cell lung cancer treated with gefitinib 250 mg/day orally, and results were correlated with treatment-related adverse effects. RESULTS: Forty (53.3%) patients harbored c.421A ABCG2 on at least one allele, while the remaining 35 (46.7%) were wild type for c.421C > A. No significant group difference was observed in frequency of gefitinib-related diarrhea or other adverse effects. In addition, the only one patient homozygous for the c.421A allele in this study was not affected with gefitinib-induced diarrhea or interstitial lung disease. Two patients (2.7%) were found to harbor the c.376T allele heterozygously. One of the two patients harbored both the c.376T and the c.421A genotypes on distinct alleles. Gefitinib-related interstitial lung disease and severe diarrhea were noted in neither of the two patients. CONCLUSIONS: In this Japanese population, we did not find an evident association between ABCG2 polymorphisms, c.376C > T and c.421C > A, and susceptibility to gefitinib-induced adverse effects.

Breast cancer resistance protein/ABCG2 is differentially regulated downstream of extracellular signal-regulated kinase.

Breast cancer resistance protein (BCRP)/ABCG2 is a drug efflux pump responsible for multidrug resistance in cancer cells. We report that dephosphorylation of extracellular signal-regulated kinase (ERK) by treatment with mitogen-activated protein kinase/ERK kinase (MEK) inhibitors causes two opposing effects, transcriptional upregulation and prompted protein degradation of endogenous BCRP in breast cancer MCF-7 cells. Endogenous BCRP was eventually found to be upregulated. Conversely, treatment with epidermal growth factor was associated with its downregulation in the cells. MEK inhibitors also caused prompted degradation of exogenous BCRP in MCF-7 and gastric cancer NCI-N87 cells that express exogenous BCRP without affecting its transcriptional levels, and potentiated anticancer agents in the cells. A lysosomal inhibitor abolished this prompted degradation of exogenous BCRP, but a proteasome inhibitor did not. Inhibition of p90 ribosomal protein S6 kinase (RSK), one of the downstream effectors of ERK, resulted in transcriptional upregulation of endogenous BCRP but did not affect the protein degradation of exogenous BCRP. The data suggest that BCRP expression is differentially regulated downstream of the MEK-ERK pathway, transcriptionally upregulated through the inhibition of the MEK-ERK-RSK pathway, and posttranscriptionally downregulated through the inhibition of the MEK-ERK-non-RSK pathway. Although the immediate downstream effector of ERK remains to be elucidated, the data provide new insights into regulatory mechanisms of BCRP activity and may assist the development of BCRP-specific expression modulators.

A 1 GHz integrated circuit with carbon nanotube interconnects and silicon transistors.

Due to their excellent electrical properties, metallic carbon nanotubes are promising materials for interconnect wires in future integrated circuits. Simulations have shown that the use of metallic carbon nanotube interconnects could yield more energy efficient and faster integrated circuits. The next step is to build an experimental prototype integrated circuit using carbon nanotube interconnects operating at high speed. Here, we report the fabrication of the first stand-alone integrated circuit combining silicon transistors and individual carbon nanotube interconnect wires on the same chip operating above 1 GHz. In addition to setting a milestone by operating above 1 GHz, this prototype is also a tool to investigate carbon nanotubes on a silicon-based platform at high frequencies, paving the way for future multi-GHz nanoelectronics.

The CD155/poliovirus receptor enhances the proliferation of ras-mutated cells.

Stimulation of the CD155/poliovirus receptor, which localizes in the cell-matrix and at cell-cell junctions, inhibits cell adhesion and enhances cell migration. Necl-5, a mouse homolog of CD155, is implicated in the formation of adherence junctions. Recently, Necl-5 has also been found to enhance cell proliferation via the stimulation of serum and platelet-derived growth factor through the Ras-Raf-MEK-ERK signaling pathway. In our present study, we find that CD155 significantly enhances the serum-induced cell proliferation of NIH3T3 cells which have been transformed by an oncogenic Ras (V12Ras-NIH3T3), but not the parental cells. CD155 expression in V12Ras-NIH3T3 cells is also found to upregulate cyclin D2, downregulate p27(Kip1) and shorten the G0/G1 phase of the cell cycle. An inhibitor of focal adhesion kinase does not reduce this CD155-mediated enhancement of V12Ras-NIH3T3 cell proliferation. The expression of CD155DeltaCP, which lacks the cytoplasmic region including the immunoreceptor tyrosine-based inhibitory motif (ITIM), has a reduced ability to enhance the serum responsiveness of V12Ras-NIH3T3 cells, suggesting that the ITIM might be required for this effect of CD155. In addition, the overexpression of exogenous CD155 enhances the serum responsiveness of HT1080 cells, which harbor a mutant N-ras gene. On the other hand, siRNA-induced knockdown of endogenous CD155 and/or CD155DeltaCP expression significantly repress the serum responsiveness of DLD-1 cells, which express endogenous CD155 and harbor a mutant K-ras gene, suggesting that this mutant may function in a dominant negative manner. Taken together, our present data suggest that CD155, at least in part, enhances the proliferation of ras-mutated cells.