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Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma
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Georgia Levidou Dimitrios Theodorou Nikolaos V. Michalopoulos Efstratios Patsouris Angelica A. Saetta 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2015,123(8):639-647
Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings. 相似文献
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Anand Dayama Nikolaos Tsilimparis Stephen Kolakowski Nathaniel M. Matolo Misty D. Humphries 《Journal of vascular surgery》2019,69(1):156-163.e1
Background
Chronic limb-threatening ischemia (CLTI), defined as ischemic rest pain or tissue loss secondary to arterial insufficiency, is caused by multilevel arterial disease with frequent, severe infrageniculate disease. The rise in CLTI is in part the result of increasing worldwide prevalence of diabetes, renal insufficiency, and advanced aging of the population. The aim of this study was to compare a bypass-first with an endovascular-first revascularization strategy in patients with CLTI due to infrageniculate arterial disease.Methods
We reviewed the American College of Surgeons National Surgical Quality Improvement Program targeted lower extremity revascularization database from 2012 to 2015 to identify patients with CLTI and isolated infrageniculate arterial disease who underwent primary infrageniculate bypass or endovascular intervention. We excluded patients with a history of ipsilateral revascularization and proximal interventions. The end points were major adverse limb event (MALE), major adverse cardiovascular event (MACE), amputation at 30 days, reintervention, patency, and mortality. Multivariable logistic regression was used to determine the association of a bypass-first or an endovascular-first intervention with outcomes.Results
There were 1355 CLTI patients undergoing first-time revascularization to the infrageniculate arteries (821 endovascular-first revascularizations and 534 bypass-first revascularizations) identified. There was no significant difference in adjusted rate of 30-day MALE in the bypass-first vs endovascular-first revascularization cohort (9% vs 11.2%; odds ratio [OR], 0.73; 95% confidence interval [CI], 0.50-1.08). However, the incidence of transtibial or proximal amputation was lower in the bypass-first cohort (4.3% vs 7.4%; OR, 0.60; CI, 0.36-0.98). Patients with bypass-first revascularization had higher wound complication rates (9.7% vs 3.7%; OR, 2.75; CI, 1.71-4.42) compared with patients in the endovascular-first cohort. Compared with the endovascular-first cohort, the incidence of 30-day MACE was significantly higher in bypass-first patients (6.9% vs 2.6%; adjusted OR, 3.88; CI, 2.18-6.88), and 30-day mortality rates were 3.23% vs 1.8% (adjusted OR, 2.77; CI, 1.26-6.11). There was no difference in 30-day untreated loss of patency, reintervention of treated arterial segment, readmissions, and reoperations between the two cohorts. In subgroup analysis after exclusion of dialysis patients, there was also no significant difference in MALE or amputation between the bypass-first and endovascular-first cohorts.Conclusions
CLTI patients with isolated infrageniculate arterial disease treated by a bypass-first approach have a significantly lower 30-day amputation. However, this benefit was not observed when dialysis patients were excluded. The bypass-first cohort had a higher incidence of MACE compared with an endovascular-first strategy. These results reaffirm the need for randomized controlled trials, such as the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL-2) trial and Best Endovascular vs Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI), to provide level 1 evidence for the role of endovascular-first vs bypass-first revascularization strategies in the treatment of this population of challenging patients. 相似文献6.
Christos Varounis Nikolaos Dagres Themistoclis Maounis Demosthenes Panagiotakos Dennis V Cokkinos 《Europace : European pacing, arrhythmias, and cardiac electrophysiology》2007,9(8):633-637
AIMS: The aim of this study was to investigate the significance of simple 24-h Holter (24H) data after electrical cardioversion (CV) for atrial fibrillation (AF) recurrence. METHODS: We prospectively studied 47 consecutive patients subjected to CV, who successfully converted to sinus rhythm. All underwent echocardiography and 24H after CV. AF recurrence was studied at 14 days and 1 month by second 24H or by interim report of AF. RESULTS: About 53.2% remained in sinus rhythm (group I) and the rest recurred to AF (group II). Group I had fewer atrial premature complexes per hour (APC/h) (P = 0.002) and lower maximum (max HR), average, and minimum heart rates compared with group II (all Ps < 0.05). The optimal value of APC/h and max HR with best sensitivity and specificity was 32 APC/h and 90 bpm, respectively. These findings were the predictors of AF recurrence [hazard ratio (HR) = 4.5 with 95% CI = 1.7-11.7 and HR = 4.3 with 95% CI = 1.7-10.9, respectively]. Patients with the combination of both predictors had greater HR of AF recurrence compared with those with < 32 APC/h and max HR < 90 bpm (HR = 8.8 with 95% CI = 2.5-31.4). CONCLUSION: Patients with frequent APC/h and high max HR are at high risk for 1-month AF recurrence after electrical CV. 相似文献
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Davangere P Devanand Christian G Habeck Matthias H Tabert Nikolaos Scarmeas Gregory H Pelton James R Moeller Brett D Mensh Tyler Tarabula Ronald L Van Heertum Yaakov Stern 《Neuropsychopharmacology》2006,31(6):1327-1334
Temporoparietal and posterior cingulate metabolism deficits characterize patients with Alzheimer's disease (AD). A H(2)(15)O resting PET scan covariance pattern, derived by using multivariate techniques, was previously shown to discriminate 17 mild AD patients from 16 healthy controls. This AD covariance pattern revealed hypoperfusion in bilateral inferior parietal lobule and cingulate; and left middle frontal, inferior frontal, precentral, and supramarginal gyri. The AD pattern also revealed hyperperfusion in bilateral insula, lingual gyri, and cuneus; left fusiform and superior occipital gyri; and right parahippocampal gyrus and pulvinar. In an independent sample of 23 outpatients with mild cognitive impairment (MCI) followed at 6-month intervals, the AD pattern score was evaluated as a predictor of cognitive decline. In this MCI sample, an H2(15)O resting PET scan was carried out at baseline. Mean duration of follow-up was 48.8 (SD 15.5) months, during which time six of 23 MCI patients converted to AD. In generalized estimating equations (GEE) analyses, controlling for age, sex, education, and baseline neuropsychological scores, increased AD pattern score was associated with greater decline in each neuropsychological test score over time (Mini Mental State Exam, Selective Reminding Test delayed recall, Animal Naming, WAIS-R digit symbol; Ps<0.01-0.001). In summary, a resting PET covariance pattern previously reported to discriminate AD patients from control subjects was applied prospectively to an independent sample of MCI patients and found to predict cognitive decline. Independent replication in larger samples is needed before clinical application can be considered. 相似文献
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Nikolaos Roidis Vasilios ZachosGeorge Basdekis M.D. Michael HantesLubna Khaldi M.D. Konstantinos Malizos M.D. 《Arthroscopy》2007
A 50-year-old woman presented with a 5-year history of mild pain in her right knee, which had increased over the last 2 years. A palpable mass over the anterolateral aspect of the knee was obvious and the last 3 months she was experiencing locking episodes with consequent knee effusion. The differential diagnosis was driven between meniscal cyst, pigmented villonodular synovitis, synovial sarcoma, synovial chondromatosis, and aneurysm. After a diagnostic arthroscopy, the lesion was excised by a limited lateral arthrotomy. The pathologic findings revealed a synovial cyst. Intra-articular synovial cysts are uncommon, nonsymptomatic, and mostly incidental findings on magnetic resonance imaging (MRI) and arthroscopy. This lateral meniscus synovial cyst (2.5 × 2.5 cm) was enlarged within the intracondylar notch and produced disabling knee symptoms. The peculiarity of this lesion was the tumor-like appearance: its large size, the progress of symptoms, and the multilobulated, nonhomogenous signal on the MRI scan. One year postoperatively, the patient is asymptomatic and the MRI obtained at 6 months revealed no remnant of the fully excised cyst. 相似文献
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