Adenosine Diphosphate Receptor Antagonist Clopidogrel Sulfate Attenuates LPS-Induced Systemic Inflammation in a Rat Model. Shock 35(3):289Y292, 2011.To the Editor: We read with great interest the study by Hagiwara et al. (1), BAdenosine Diphosphate Receptor Antagonist Clopidogrel Sulfate Attenuates LPS-Induced Systemic Inflammation in a Rat Model,[ which found that a pretreatment with clopidogrel (CS) reduced the LPS-induced increase in proinflammatory cytokines IL-6 and TNF-! and reduced LPS-induced expression of high mobility group box 1 (HMGB1) in lung and liver tissues in LPS-treated rats. In addition, LPS-induced histological alterations (e.g., interstitial edema, inflammatory cell infiltration, etc.) were attenuated in CS-pretreated rats.Although we observed similar results in LPS and sepsis models (2, 3), we could further demonstrate a potential for antiplatelet drugs in critically ill patients: In 2 clinical retrospective studies (2, 4), we tested the hypothesis whether antiplatelet drugs might favorably affect outcome in patients at risk for organ dysfunction: The first analysis included 615 patients consecutively admitted to an ICU. Approximately 25% of those patients had received a continous medication with antiplatelet drugs (acetylsalicylic acid, clopidogrel) for secondary prevention of vascular disease before admission. The impact of antiplatelet drugs and established risk factors on mortality were assessed by logistic regression and 2 Â 2 table analysis. Patients on antiplatelet drugs were markedly older and presented higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on ICU admission. Both, logistic regression analysis and comparison of APACHE II score-matched samples of patients (APACHE II 920) by 2 Â 2 table analysis indicated that antiplatelet drugs were associated with substantially lower mortality in internal medicine patients (odds ratios of 0.20 and 0.36, respectively).In a second retrospective analysis, 224 patients who were consecutively admitted to a University Hospital for communityacquired pneumonia over a period of 5 years were enrolled. Twenty percent of those patients received antiplatelet drugs (acetylsalicylic acid, thienopyridines) for secondary prevention of cardiovascular disease. Patients with antiplatelet drugs were about 12 years older but did not differ in Sepsis-Related Organ Failure Assessment score and routine laboratory parameters at admission. Antiplatelet drugs were associated with decreased odds ratios for admission to ICU according to logistic regression in all patients as well as in age-matched subgroups (odds ratio, 0.32 and 0.19, respectively). In age-matched subgroups, the use of antiplatelet drugs was also associated with a shorter stay in the hospital (13.9 T 6.2 vs. 18.2 T 10.2 days; P G 0.02).Our data add evidence to the previously mentioned study by Hagiwara et al. and suggest that pretreatment with CS or other antiplatelet drugs may indeed have value as a potential therapeutic tool in systemic inflammation. REFERENCES 1. Hagiwara ...
Tumors of the craniocervical junction (CCJ) are complicated pathologies with high patient mortality or low quality of life. In the pediatric population, these tumors are less prevalent, with various symptomatic presentations that include motor and neurological manifestations. Three of the most common neoplasms at the CCJ in children are meningiomas, schwannomas, and chordomas. In this review, we will characterize the tissue biomarkers, clinical presentation, treatment methods, and surgical outcomes for these pediatric tumors at the CCJ. A comprehensive literature review was used using the PubMed Database. Keywords used were "craniocervical junction", "pediatric", "meningiomas", schwannomas", and "meningiomas". Articles that were not related to the CCJ, included only adult cases, and non-English studies were filtered. Our search yielded a total of 11 studies, with a total of 239 pediatric patients with tumors at the CCJ. These studies were broken down as five for meningiomas, one for schwannomas, and eight for chordomas. In conclusion, resection of pediatric neoplasms at the CCJ is challenging due to anatomical limitations and the size of the patient. Within the CCJ, chordomas were the most prevalent tumor type, with schwannomas being the least prevalent. Literature findings indicate that genetic mutations of the NF2 gene associated with neurofibromatosis type II, as well as incomplete tumor resection, are predictors of poor outcomes. Further developments of monoclonal antibody chemotherapy and endoscopic approaches could expand treatment options for aggressive pediatric neoplasms at the skull base.
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