Immunomodulation in sepsis: state of the art and future perspective

Despite advances in supportive care of critically ill patients, sepsis remains an important cause of death worldwide. More than 750,000 individuals develop severe sepsis in North America annually, with a mortality rate varying between 35 and 50%. Over recent years, numerous efforts have been committed to understanding the pathophysiology of septic syndrome, as well as attempts to intervene in the inflammatory cascade with the aim of altering the outcome of the syndrome and to improve survival. Not all of these attempts have been successful. Issued guidelines by the International Sepsis Forum have incorporated only the use of corticosteroids, tight glycemic control and the use of recombinant activated protein C as recommendations for the management of the septic patient along with the initial resuscitation and infection-site control measures. These strategies along, with novel attempts of immunomodulation, are thoroughly reviewed in this article.     

Endoscopic ultrasonography for gastric submucosal lesions

Gastric submucosal tumors(SMTs) are a rather frequent finding,occurring in about 0.36%of routine upper GIendoscopies.Endoscopic ultrasonography(EUS) has emerged as a reliable investigative procedure for evaluation of these lesions.Diagnostic EUS has the ability to differentiate intramural tumors from extraluminal compressions and can also show the layer of origin of gastric SMTs.Tumors can be further characterized by their layer of origin,echo pattern and margin.EUS-risk criteria of their malignant potential are presented,although the emergence of EUS-FNA has opened new indications for transmural tissue diagnosis and expanded the possibilities of EUS in SMTs of the stomach.Tissue diagnosis should address whether the SMT is a Gastrointestinal stromal tumour(GIST) or another tumor type and evaluate the malignant potential of a given GIST.However,there seems to be a lack of data on the optimal strategy in SMTs suspected to be GISTs with a negative EUS-FNA tissue diagnosis.The current management strategies,as well as open questions regarding their treatment are also presented.     

Primary hepatic gastrinoma: Report of a case and review of literature

Primary hepatic gastrinoma is a very rare ectopic gastrinoma with less than 20 cases reported worldwide. We report the case of a patient with hypergastrinemia who was subjected to exhaustive preoperative and intraoperative imaging and also careful surgical exploration of the duodenum and pancreas which failed initially to identify the primary tumour. Eventually the patient was subjected to left liver lobectomy,as a small palpable lesion was noted intraoperatively. The diagnosis of gastrinoma requires a high index of clinical suspicion and the flawless cooperation of many specialties.     

Wrist injuries in young adults: The diagnostic impact of CT and MRI

Purpose

To evaluate the diagnostic impact of MRI or/and multidetector CT in young patients with wrist injury and inconclusive or negative clinical examination and X-rays and to analyze variations in imaging strategies between a district general hospital (GH) and a university hospital (UH).

Materials and methods

A retrospective analysis of 34 young patients (mean age 23 years) with wrist trauma who underwent CT or/and MRI was performed. The injury was acute in 24, and chronic in 10 patients. Twenty-two patients were from a GH and 12 from a UH. Two experienced musculoskeletal radiologists blindly reviewed the imaging studies. The effect of cross-sectional imaging on patient care and treatment plan was evaluated.

Results

In 9 of 34 patients one or more fractures were diagnosed on cross-sectional imaging. The scaphoid was fractured in four patients, the lunate and/or the trapezium in three patients, the scaphoid together with the lunate in one patient, and finally the distal radius in one patient. Ligamentous trauma was identified solely on MRI in 11 patients (involving the TFCC in eight cases). In four patients with both imaging methods, CT revealed one fracture of the trapezium not seen on MRI, and one scapholunate fracture with MRI findings of distal radial fracture only. In two patients with normal CT, MRI revealed bone marrow oedema of the scaphoid in one and of the distal radius, lunate and triquetrum in the other.

Conclusion

Both CT and MRI might be considered in patients with acute or chronic wrist injury, clinical dilemma and normal initial radiographs, depending on the availability and the individual institution policies.     

Infrared irradiation alters the expression of matrix metalloproteinases and glycosaminoglycans in the cornea and crystalline lens

Background

Prolonged exposure to infrared (IR) radiation is associated with different types of damage to cornea and lens. The aim of our study was to investigate the effect of acute and chronic exposure to IR radiation on the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 and on the expression of glycosaminoglycans (GAG) in the rabbit cornea and crystalline lens.

Methods

New Zealand rabbits were subjected to IR radiation for 4 months (chronic exposure to IR) or to normal light (control group). In experiments regarding acute exposure, animals were subjected to IR radiation or normal light for 12 h, in the presence of 0.1 % diclofenac sodium (eye drops instilled in the right eye of animals) or saline (instilled in the left eye of animals). The cornea and lens were dissected away and homogenized. The activity of MMP-2 and MMP-9 was assayed by gelatine zymography. Total GAG were isolated from tissue specimens after lipid extraction and extensive digestion with pronase and DNase and characterized by treatment with GAG-degrading enzymes, followed by electrophoresis on cellulose acetate membranes.

Results

Acute or chronic exposure to IR radiation induced the activity of MMP-2 in cornea and lens, whereas only acute IR radiation increased the content of heparan sulphate in crystalline lens. Local administration of diclofenac sodium did not prevent the above effects of acute IR radiation.

Conclusions

The detrimental effects of excessive or prolonged exposure of the eyes to IR radiation are associated with induced activity of MMP-2 in cornea and lens and alterations in the content of heparan sulphate in lens. Thus, MMP and GAG may offer alternative targets for pharmacological intervention to confront ocular damages associated with IR radiation.     

Clopidogrel vs. aspirin treatment on admission improves 5-year survival after a first-ever acute ischemic stroke. data from the Athens Stroke Outcome Project

Background and Aims

We undertook this study to compare the impact of aspirin vs. clopidogrel treatment on 5-year survival of patients experiencing a first-ever acute ischemic noncardioembolic stroke.

Methods

This was a retrospective study involving patients with an acute ischemic stroke who had an indication for antiplatelet therapy (atherothrombotic, lacunar and cryptogenic stroke subtype). A total of 1228 (383 women) hospitalized due to an acute first-ever stroke and receiving aspirin (n = 880) or clopidogrel (n = 348) were finally involved. To determine the factors that independently predict 5-year survival statistical analysis including the Kaplan-Meier survival curve and multifactorial analysis (Cox regression) was performed.

Results

Subjects treated with clopidogrel had improved 5-year survival compared with those receiving aspirin (log rank test: 16.4, p <0.0001). The difference in survival was evident as early as 6 months from index stroke: cumulative survival 93.8% for aspirin vs. 97% for clopidogrel (log rank test: 4.01, p = 0.045). The composite cardiovascular event (including stroke recurrence, myocardial infarction, unstable angina, coronary revascularization, aortic aneurysm rupture, peripheral atherosclerotic artery diseases, and sudden death) rates were lower in the clopidogrel group (n = 60, 17.2%) compared with the aspirin (n = 249, 28.3%) group (log rank test: 12.4, p <0.0001). This preferential effect of clopidogrel over aspirin was independent of age, gender, presence of cardiovascular disease other than stroke or cardiovascular risk factors as well as irrespective of the severity of stroke and days of hospitalization.

Conclusions

This study supports that clopidogrel is superior to aspirin in preventing death and cardiovascular events after an acute noncardioembolic ischemic stroke.