Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection.

Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).

Acute effects of isosorbide dinitrate and nicorandil on the coronary slow flow phenomenon.

BACKGROUND: Microvascular dysfunction has been proposed as the most likely mechanism of the coronary slow flow phenomenon (CSFP). OBJECTIVES: To determine the effects of isosorbide dinitrate and nicorandil on the CSFP. METHODS: Changes in thrombolysis in myocardial infarction (TIMI) frame count following the intracoronary administration of isosorbide dinitrate and nicorandil were assessed in 11 patients with the CSFP. RESULTS: After the administration of isosorbide dinitrate, the median TIMI frame count decreased to 32 (range 20-60) [p = 0.003], which was lower than that of the control [43 (29-73)]. The count decreased further to 25 (12-34) [p = 0.041] after the administration of nicorandil. The count after the subsequent administration of contrast medium was increased to 32 (20-49) [p = 0.03]. CONCLUSIONS: These angiographic findings indicate that the intracoronary administration of nicorandil is superior to isosorbide dinitrate with regard to improving the CSFP. These findings suggest that microvascular spasm is the main factor in the pathogenesis of the CSFP.

Leukemic transformation of Langerhans cell sarcoma.

A 57-year-old man became aware of left supraclavicular lymph node swelling, which was subsequently diagnosed as Langerhans cell sarcoma, based on a positive immunophenotype for CD1a, S-100 protein, and langerin, and histologically bizarre pleomorphism. The tumor became leukemic 3 months later. Despite intensive chemotherapy, he died of disease progression 7 months after the initial diagnosis. Tumor cells in the leukemic phase expressed CD5, CD7, CD13, CD33, CD34, CD68, and CD123. These findings suggested leukemic transformation from Langerhans cell sarcoma. Leukemic transformation may be a clinical manifestation of advanced Langerhans cell sarcoma, and should be differentiated from acute myelogenous leukemia.