Post-Operative Dexmedetomidine-Based Sedation After Uneventful Intracranial Surgery for Unruptured Cerebral Aneurysm: Comparison with Propofol-Based Sedation

Background  

Clinical applications of dexmedetomidine (DEX) for neurosurgical procedures have not been adequately investigated. This study aimed to test the use of DEX infusion, alone or as an adjunct to propofol infusion, as compared to propofol infusion in patients with an unruptured cerebral aneurysm after uneventful intracranial procedures.     

Low-grade endotoxemia contributes to chronic inflammation in hemodialysis patients: examination with a novel lipopolysaccharide detection method

Chronic inflammation has recently been proposed to play a major role in the development of cardiovascular disease and mortality among advanced chronic kidney disease (CKD) patients; however, why advanced CKD promotes chronic inflammation is still unclear. We hypothesized that a very low level of plasma endotoxin (lipopolysaccharide [LPS]) contributes to chronic inflammation in advanced CKD patients. We measured the plasma LPS levels using a novel LPS detection method (ESP method, a method for endotoxin detection using laser scattering photometry) concurrently with serum C-reactive protein (CRP) levels and various blood tests in 17 stable hemodialysis (HD) patients. As a result, the median LPS levels measured by the ESP method was 0.23 pg/mL (range, 0.01-3.89) (inflow, start of HD), 0.22 pg/mL (<0.01-9.97) (outflow, start of HD), 0.37 pg/mL (<0.01-7.42) (inflow, end of HD), and 1.07 pg/mL (<0.01-10.66) (dialysate), respectively; statistically significant differences were not detected between them. The predialysis median CRP level was 0.19 mg/dL (0.04-3.02). The logarithm of plasma LPS independently correlated with serum CRP (R = 0.595, P = 0.0103). In multiple (forward stepwise) regression analysis, in which CRP was determined to be the criterion variable, LPS (log), albumin, and the white blood cell count were adopted as independent explanatory variables (R = 0.401, -0.397 and 0.387, respectively). In conclusion, the present study revealed a significant relationship between LPS and CRP using the novel ESP method, and suggested that very low-grade endotoxemia is contributing to systemic inflammation in HD patients.     

Selection of acute blood purification therapy according to severity score and blood lactic acid value in patients with septic shock

Aim:

As an alternative method for acute blood purification therapy, continuous venovenous hemodiafiltration (CVVHDF) has been reported as an effective clinical treatment for critically ill patients, but the optimal column for performing CVVHDF remains controversial.

Patients and Methods:

We used direct hemoperfusion using a polymyxin B-immobilized fiber column (DHP-PMX) to treat 88 patients with septic shock. To determine the optimal acute blood purification therapy, we subsequently divided the patients into three groups: the first group underwent CVVHDF using a polymethylmethacrylate membrane hemofilter (PMMA) after undergoing DHP-PMX (28 cases), the second group underwent CVVHDF using a polyacrylonitrile membrane hemofilter (PAN) after undergoing DHP-PMX (26 cases), and the third group did not undergo CVVHDF after undergoing DHP-PMX (34 cases).

Results:

The overall survival rate was 54.5%, and patient outcome was significantly related to the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the sepsis-related organ failure assessment (SOFA) score, and the blood lactic acid value before treatment (all P<0.0001). Only the PMMA-CVVHDF group showed a better outcome (survival rate of 78.6%) compared with the other groups (P = 0.0190). In addition, only the PMMA-CVVHDF group showed a significant improvement in the blood lactic acid level on day 3 (P = 0.0011).

Conclusion:

Our study suggests that the PMX column might be effective during the early phase of septic shock, before a high level of lactic acid is present. Furthermore, a PMMA column might be the most useful column for performing CVVHDF after DHP-PMX treatment, as suggested by the blood lactic acid value.     

Whether to maintain or strengthen the treatment for pyoderma gangrenosum ulcerative type may depend on the response after two to four‐week treatment intervention: The outcome of three cases with details clinical course

Determining whether the treatment intensity needs to be increased or can be maintained at a constant level may be suggested after 2–4 weeks of treatment. The use of TNF‐α inhibitor, removal of necrotic tissue, and skin grafting may promote epithelialization.     

Cell surface tetraspanin CD9 mediates chemoresistance in small cell lung cancer

Small cell lung cancer (SCLC) is an aggressive malignancy with extremely high mortality due to the appearance of widespread metastases early in its clinical course and rapid acquisition of chemoresistance after initial therapy. A theory of cell adhesion-mediated drug resistance is thought to be a principal mechanism in which extracellular matrix proteins provide a survival advantage against cytotoxic drug-induced apoptosis. We found that the tetraspanin family member CD9 was expressed preferentially in SCLC tumors and metastases from three of seven relapsed patients, whereas chemona?ve primary tumors from 16 patients were CD9 negative with only one exception. Additionally, CD9 was highly expressed on SCLC cell lines rendered resistant to cisplatin or etoposide, and was upregulated in parental chemosensitive cells within 48 hours after exposure to either of these compounds. CD9-expressing chemoresistant SCLC cells adhered more tightly to fibronectin via β1 integrin, but they were less motile than the respective chemosensitive parental lines. Notably, treatment of the chemoresistant cells with chemokine CXCL12 downregulated CD9 and transiently restored motility. Moreover, selective targeting of CD9 by treatment with specific monoclonal antibody ALB6 or a small interfering RNA triggered apoptosis in the chemoresistant cells. Taken together, our findings implicate CD9 in the cell adhesion-mediated drug resistance mechanism, highlighting CD9 as an attractive therapeutic target to improve therapeutic outcomes in SCLC.