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21.
Membrane trafficking processes are presumably vital for axonal regeneration after injury, but mechanistic understanding in this regard has been sparse. A recent loss-of-function screen had been carried out for factors important for axonal regeneration by cultured cortical neurons and the results suggested that the activity of a number of Rab GTPases might act to restrict axonal regeneration. A loss of Rab27b, in particular, is shown to enhance axonal regeneration in vitro, as well as in C. elegans and mouse central nervous system injury models in vivo. Possible mechanisms underlying this new finding, which has important academic and translational implication, are discussed.  相似文献   
22.

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Methods

In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).

Results

After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).

Conclusions

This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.  相似文献   
23.

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   
24.
目的探讨化浊解毒方治疗溃疡性结肠炎(UC)的治疗作用及机制。方法120例UC患者按照随机数字表法分为观察组、对照组各60例。观察组予中药化浊解毒方口服,每日1剂,早晚2次温服;对照组予美沙拉嗪肠溶片口服,1.0 g/次,3次/d。2组疗程均4周。对比2组治疗前后Geboes指数、结肠镜下黏膜表现、生活质量评分、疾病活动指数及血清炎性因子IL-8、IL-35水平,凝血指标血清FIB水平,统计治疗后1年内复发情况。结果治疗后,观察组Geboes指数、疾病活动指数及血清炎性因子IL-8水平、凝血指标血清FIB水平均较本组治疗前降低,生活质量评分、血清炎性因子IL-35水平升高(P<0.05);且观察组治疗后疾病活动指数及血清炎性因子IL-8水平、凝血指标血清FIB水平均低于对照组,生活质量评分、血清炎性因子IL-35水平均高于对照组(P<0.05)。与对照组相比,治疗组糜烂、溃疡改善不明显(P>0.05),充血水肿、颗粒样变等肠镜表现改善情况均优于对照组(P<0.05)。治疗结束1年观察组复发率为10.64%,对照组为23.53%,2组差异有统计学意义(P<0.05)。结论化浊解毒方能改善UC患者临床症状,修复肠黏膜病理损伤,降低复发率;其机制可能与调节血清炎性因子IL-8、IL-35和凝血因子FIB水平有关。  相似文献   
25.
Conclusion  Several quality-control measures take place before (patient and camera preparation) and during SPECT acquisition to achieve high-quality images. Not uncommonly, technologists and physicians are left with suboptimal images that have to be addressed to reach the “right answer” for patient diagnosis and hence management. In many cases patients may be reimaged, especially if the problem is detected early, but in other cases either the patient has left the nuclear laboratory or there is an inevitable problem that, even with reimaging, will not be resolved. In these situations the technologist and physician have to seek the available techniques to obtain the best images possible. These resources are discussed in this issue as an aid in quality control to obtain the best possible images.  相似文献   
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BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly malignant tumour with a poor prognosis. Patients present with signs of steroid hormone excess (e.g., Cushing's syndrome) or symptoms due to an abdominal mass. DIAGNOSIS: In case of an adrenal mass, hormonal workup before surgery is required for differential diagnosis, perioperative management, and for follow-up. The imaging of choice is CT or MRI with MRI being of additional use when invasion of big vessels is suspected. Apart from that, the use of 18-FDG-PET is becoming increasingly established. TREATMENT: Surgical resection is the therapeutic option of choice in stages 1 - 3. In stage 4, the adrenolytic compound mitotane is part of the first-line treatment, but often needs to be combined with cytotoxic chemotherapy. Most patients will eventually have a recurrence, so adjuvant treatment (mitotane/tumour bed radiation) has to be considered in high risk patients, even if randomized controlled trials on adjuvant treatment are still lacking. STRUCTURAL PROGRESS: Several national and European structures have recently been established in order to increase our knowledge of ACC, improve therapeutic options and diagnostic procedures, and promote research. GANIMED, as a Germany-wide network of experts on adrenal diseases, has been founded allowing for improved gathering of data and joint studies. ENSAT (European Network for the Study of Adrenal Tumours) has been brought to life, aiming at European standards for therapy, diagnosis and tumour banking. Since 2003, patients can be enrolled in the German ACC Registry. France and Italy have also developed a central registry to collect nationwide data from patients with ACC. For the first time, patients with metastatic/unresectable ACC can participate in a prospective controlled randomized trial comparing two different cytotoxic chemotherapy regimes (FIRM-ACT).  相似文献   
30.
BACKGROUND: Radioiodine therapy (RIT) combined with glucocorticoids is an effective therapy for Graves' disease, but it is debatable whether glucocorticoids should be applied in patients without Graves' ophthalmopathy (GO). METHODS: The effect of 0.4 - 0.5 mg prednisone every second day over a period of 5 weeks after RIT was monitored over a follow-up period of at least 12 months after RIT. A questionnaire was sent to 186 consecutive patients without GO concerning eye symptoms after RIT. 148 patients (80 %) answered. If eye symptoms had occurred after RIT, additional clinical examination was carried out at our outpatient clinic. The primary endpoint was the absence or onset of GO within the first year after RIT. RESULTS: Within 12 months after RIT the examination confirmed GO in 5 out of 148 patients (3.4 %). In all cases the symptoms were transient. No adverse reaction to the use of prednisone after RIT was noted. CONCLUSIONS: The risk of new GO in the first year after RIT was low and the clinical course of GO was mild when RIT was combined with a low-dose glucocorticoid regimen. Preventive administration of glucocorticoids can therefore be recommended in patients with Graves' disease even without evident GO.  相似文献   
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