Background and purpose
We investigated the effect of celecoxib, a selective inhibitor of cyclo‐oxygenase 2, in patients with intracerebral hemorrhage (ICH).
Methods
We conducted a multicenter, ...randomized, controlled, and open with blinded end‐point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end‐point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut‐off value, 20%).
Results
The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end‐point analysis using cut‐off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end‐points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow‐up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058).
Conclusions
In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.
We investigate the potential of liquid hydrogen storage (LH2) on-board Class-8 heavy duty trucks to resolve many of the range, weight, volume, refueling time and cost issues associated with 350 or ...700-bar compressed H2 storage in Type-3 or Type-4 composite tanks. We present and discuss conceptual storage system configurations capable of supplying H2 to fuel cells at 5-bar with or without on-board LH2 pumps. Structural aspects of storing LH2 in double walled, vacuum insulated, and low-pressure Type-1 tanks are investigated. Structural materials and insulation methods are discussed for service at cryogenic temperatures and mitigation of heat leak to prevent LH2 boil-off. Failure modes of the liner and shell are identified and analyzed using the regulatory codes and detailed finite element (FE) methods. The conceptual systems are subjected to a failure modes and effects analysis (FMEA) and a safety, codes, and standards (SCS) review to rank failures and identify safety gaps. The results indicate that the conceptual systems can reach 19.6% useable gravimetric capacity, 40.9 g-H2/L useable volumetric capacity and $174–183/kg-H2 cost (2016 USD) when manufactured 100,000 systems annually.
•LH2 is promising fuel for heavy truck transportation with long autonomy and low cost.•High H2 weight fraction (19.6%) promises autonomy and little impact on cargo capacity.•High H2 system storage density (>40 gH2/L) minimizes impact on trailer cargo volume.•Low system cost at $174-$183 per kg of useable H2 reduces impact on truck capital cost.
Migraine carries an increased risk for cardiovascular and cerebrovascular diseases that cannot be explained by traditional cardiovascular risk factors. The circulating endothelial progenitor cell ...(EPC) number is a surrogate biologic marker of vascular function, and diminished EPC counts are associated with higher cardiovascular risk. We investigated whether abnormalities in EPC levels and functions are present in migraine patients.
Consecutive headache patients (n =166) were enrolled, including those with tension type headache (TTH; n = 74), migraine without aura (MO; n = 67), and migraine with aura (MA; n = 25). EPC colony-forming units in peripheral blood samples and migratory capacity to chemoattractants (stromal cell-derived factor 1 and vascular endothelial growth factor) and cellular senescence levels were assayed in risk factor-matched subjects (n = 6 per group).
The TTH group had more cardiovascular risk factors, more headache days, and higher Framingham risk scores than the other two groups. Mean numbers of EPC colony-forming units were 47.8 +/- 24.3 in TTH, 20.4 +/-22.2 in MO, and 8.6 +/- 10.1 in MA patients (p < 0.001 in TTH vs MO; p = 0.001 in MO vs MA). EPC colony counts of normal subjects (n = 37) were not significantly different from those with TTH. Multiple linear regression models identified only MO, MA, and the presence of migraine (MO + MA) as significant predictors of EPC levels. In addition, EPCs from migraine patients (MO and MA) showed reduced migratory capacity and increased cellular senescence compared with EPCs from TTH or normal subjects.
Circulating endothelial progenitor cell (EPC) numbers and functions are reduced in migraine patients, suggesting that EPCs can be an underlying link between migraine and cardiovascular risk.
Background and purpose
Although a stroke from atherosclerosis in the basilar artery (BA) often presents with mild initial stroke severity, it has heterogeneous clinical courses. We investigated the ...efficacy of digital subtraction angiography (DSA)‐based collateral perfusion evaluation in association with long‐term outcomes of medically treated symptomatic basilar artery stenosis.
Methods
From a registry database of all consecutive patients with stroke, we included 98 medically treated patients (due to mild initial stroke severity) National Institute of Health Stroke Scale (NIHSS) scores ≤ 4; symptomatic basilar artery stenosis, 70–99% with available initial diagnostic DSA. Basilar collateral scoring was performed via the DSA, using a modified version of the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system in both the superior cerebellar artery and anterior/posterior‐inferior cerebellar artery territories (score 0–8). The outcomes were designated as the 90‐day modified Rankin Scale (mRS90) score (poor, 3–6). Student's t‐test, chi‐square test and logistic regression analyses were used to identify factors associated with a poor outcome.
Results
The median initial NIHSS score was 2 interquartile range (IQR), 0–3, median posterior circulation Alberta Stroke Program Early CT Score was 8 (IQR, 7–10), median collateral score was 7 (IQR, 7–8) and 20 (20.4%) had poor mRS90 scores. In multivariate analysis, poorer collateral scores (P = 0.003), higher NIHSS scores (P = 0.005) and lower posterior circulation Alberta Stroke Program Early CT Score (P = 0.017) were independently associated with a poor mRS90 score.
Conclusions
The DSA‐based collateral scoring of the BA large branches might predict long‐term outcome in medically treated symptomatic basilar artery stenosis with mild initial severity. Evaluation of BA collateral perfusion status might be useful to determine appropriate treatment strategies.
Objectives
Lymph node (LN) metastasis of oral cavity squamous cell carcinoma (OSCC) is associated with survival outcomes. However, the relationship between different metastatic nodal factors and ...treatment outcomes requires further elucidation. This study examined nodal factors predictive of recurrence and survival in patients with OSCC.
Methods
This prospective observational study included 157 patients with OSCC who underwent surgery between 2010 and 2015. Clinicopathological and follow‐up information were recorded. Univariate and multivariate Cox proportional hazard models were performed to identify factors associated with recurrence‐free survival, disease‐specific survival and overall survival.
Results
Sixty‐five of 157 patients (41.4%) had neck metastasis. During a median follow‐up of 46 months, any recurrences and all deaths occurred in 43 (27.4%) and 43 (27.4%) of cases, respectively. All nodal factors (LN classification, size, number and ratio) and extra‐nodal extension were significantly associated with all survival outcomes (P < .001). Multivariate analyses indicated that a tumour size >2 cm and LN ratio were independently associated with all survival (P < .05). Patients with LN ratio >0.05 had sixfold higher recurrence and mortality rates than other patients (P < .001).
Conclusion
Lymph node ratio is an independent and predictive determinant of post‐treatment recurrence and survival.
Neurovascular dysfunction and senescent endothelium contribute to the progression of Alzheimer disease (AD). Circulating angiogenic cells (CACs), such as endothelial progenitor cells (EPCs), provide ...a cellular reservoir for the endothelial replacement. To study the involvement of CACs in AD pathogenesis, we investigated the levels of CACs in patients with AD.
Consecutive patients with newly diagnosed AD (n = 55), patients with non-AD neurodegenerative diseases (n = 37), and nondemented risk factor control subjects (RF control, n = 55 and 37) were enrolled after matching for age, sex, and Framingham risk score. Peripheral blood samples were taken, and EPC colony-forming units (CFU-EPC) were cultured and counted.
The patients with AD had significantly lower CFU-EPC than the RF controls. In the patients with AD, a lower CFU-EPC was independently associated with either a lower Mini-Mental State Examination score or a higher Clinical Dementia Rating scale score, indicating a greater reduction in CFU-EPC in advanced AD. Patients with non-AD neurodegenerative diseases did not show a significant decrease in CFU-EPC levels.
Our results indicate that patients with Alzheimer disease (AD) have reduced circulating angiogenic cells, suggesting that an abnormal capacity to regenerate endothelium is associated with AD.
The benefit of surgical resection of liver metastases from gastric cancer has not been well established. The aim of this study was to evaluate the rationale for hepatic resection in patients with ...hepatic metastases from gastric cancer.
Among 10259 patients diagnosed with gastric adenocarcinoma in the Yonsei University Health System from 1995 to 2005, we reviewed the records of 58 patients with liver-only metastases from gastric cancer who underwent gastric resection regardless of hepatic surgery.
The overall 1-year, 3-year, and 5-year survival rates of 41 patients who underwent hepatic resection with curative intent were 75.3%, 31.7%, and 20.8%, respectively, and three patients survived >7 years. Of the 41 patients, 22 had complete resection and 19 had palliative resection. Between the curative and palliative resections, survival rates after curative intent were not different. The number of liver metastasis (solitary or multiple) was a marginally significant prognostic factor for survival.
Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if complete resection seems feasible after careful preoperative staging, even if complete resection is not actually achieved. Hepatic resection should be considered as an option for gastric cancer patients with hepatic metastases.
Summary
Background Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated.
Objectives To evaluate ...the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥ 5% body surface area in children or measuring ≥ 20 cm in adults.
Methods In total, 131 patients with GCMN were enrolled, with a mean age of 10·3 years (range: birth–70 years).
Results The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients < 4 years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6‐year‐old girl, a 14‐year‐old girl and a 70‐year‐old man), and the incidence rate was 990 per 100 000 person‐years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma.
Conclusions We should be aware of melanoma development from GCMN, and lifelong follow‐up is required due to the risk of melanoma arising in GCMN.
The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based ...therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC.
Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis.
Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% 95% confidence interval (CI) 17.2–34.4 for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2–30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89–9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62–9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74–1.36). The response rates were 49.1% (95% CI 39.7–58.6) and 45.9% (95% CI 36.4–55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%).
No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity.
NCT00851084, www.clinicaltrials.gov, EudraCT 2008-004178-41.
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