Validation of Michigan risk score and D-dimer to predict peripherally inserted central catheter-related thrombosis: A study of 206,132 catheter days.

BACKGROUND: The Michigan Risk Score (MRS) was the only predicted score for peripherally inserted central venous catheters (PICC) associated upper extremity venous thrombosis (UEVT). Age-adjusted D-dimer increased the efficiency for UEVT. There were no external validations in an independent cohort. METHOD: A retrospective study of adult patients with PICC insertion was performed. The primary objective was to evaluate the performance of the MRS and age-adjusted D-dimer in estimating risk of PICC-related symptomatic UEVT. The sensitivity, specificity and areas under the receiver operating characteristics (ROC) of MRS and age-adjusted D-dimer were calculated. RESULTS: Two thousand one hundred sixty-three patients were included for a total of 206,132 catheter days. Fifty-six (2.6%) developed PICC-UEVT. The incidences of PICC-UEVT were 4.9% for class I, 7.5% for class II, 2.2% for class III, 0% for class IV of MRS (p = 0.011). The incidences of PICC-UEVT were 4.5% for D-dimer above the age-adjusted threshold and 1.5% for below the threshold (p = 0.001). The areas under ROC of MRS and age-adjusted D-dimer were 0.405 (95% confidence interval (CI) 0.303-0.508) and 0.639 (95% CI 0.547-0.731). The sensitivity and specificity of MRS were 0.82 (95% CI, 0.69-0.91), 0.09 (95% CI, 0.08-0.11), respectively. The sensitivity and specificity of age-adjusted D-dimer were 0.64 (95% CI, 0.46-0.79) and 0.64 (95% CI, 0.61-0.66), respectively. CONCLUSIONS: MRS and age-adjusted D-dimer have low accuracy to predict PICC-UEVT. Further studies are needed.

Omega-3 polyunsaturated fatty acids inhibit the increase in cytokines and chemotactic factors induced in vitro by lymph fluid from an intestinal ischemia-reperfusion injury model.

OBJECTIVE: To investigate the active factors and the intervention effect of ω-3 polyunsaturated fatty acids (PUFAs) during intestinal ischemia-reperfusion (I/R) injury, which causes the inflammation of monocytes-macrophages cultured in lymph fluid and stimulated with ω-3 PUFAs. METHODS: Forty-eight Sprague-Dawley male rats were randomly divided into the following two groups: A. (N + D) group and B. (I/R + D) group. The rats in the (N + D) group were drained of lymph for 180 min; the rats in the (I/R + D) group were subjected to 60 min ischemia by clamping the superior mesenteric artery followed by 120 min reperfusion and 180 min of lymph draining. Lymph fluid from each group was further divided into 4 subgroups, respectively: lymph group (A1, B1); eicosopentaenoic acid (EPA)-treated group (A2, B2); EPA + docosahexaeonic acid (DHA)-treated group (A3, B3); and DHA-treated group (A4, B4), then cultured monocyte-macrophage cell line. RESULTS: The levels of tumor necrosis factor-α, interleukin (IL)-1 ß, IL-6, soluble cell adhesion molecule-1, chemotactic factors macrophage chemoattractant protein-1, macrophage inflammatory protein-2, and high mobility group box protein 1 in the B1 group were significantly higher than in the A1 group. Importantly, addition of EPA, EPA + DHA, and DHA to the culture media significantly reduced the levels of the above-mentioned factors. Cell stimulation with EPA, EPA + DHA, and DHA also significantly decreased the expression of Toll-like receptor 4, nuclear factor-κB p65, macrophage chemoattractant protein-1, and macrophage inflammatory protein-2 with the combined treatment of EPA and DHA showing the strongest effect. CONCLUSIONS: The factors induced in lymph during intestinal I/R injury can cause inflammation in vitro. These data provide in vitro evidence that ω-3 PUFAs provide a protective effect by reducing the inflammatory response caused by intestinal I/R lymph. Moreover, the synergism of EPA and DHA had the greatest effect, which is possibly mediated through Toll-like receptor 4 and nuclear factor-κB p65.

Moxifloxacin is non-inferior to combination therapy with ceftriaxone plus metronidazole in patients with community-origin complicated intra-abdominal infections.

Management of community-origin complicated intra-abdominal infections (cIAIs) requires surgical intervention and antimicrobial therapy. This multinational, randomised, double-blind clinical trial carried out in Asia compared the efficacy and safety of moxifloxacin monotherapy and ceftriaxone/metronidazole combination therapy in adults with confirmed or suspected cIAI. Patients received surgical intervention and either intravenous (i.v.) moxifloxacin 400 mg once daily or i.v. ceftriaxone 2 g once daily plus i.v. metronidazole 500 mg twice daily. A total of 364 patients were randomised [intent-to-treat (ITT), moxifloxacin N=180, comparator N=181; per-protocol (PP), moxifloxacin N=174, comparator N=171]. The most common cIAI diagnosis was complicated appendicitis. Moxifloxacin was non-inferior to ceftriaxone/metronidazole in terms of clinical response at test-of-cure in the PP population [clinical cure, 90.2% for moxifloxacin vs. 96.5% for ceftriaxone/metronidazole; 95% confidence interval (CI) of the difference -11.7 to -1.7] and in the ITT population (87.2% for moxifloxacin vs. 91.2% for ceftriaxone/metronidazole; 95% CI -10.7 to 1.9). Bacteriological cure rates in the microbiologically evaluable population support the clinical results (89.4% for moxifloxacin vs. 95.9% for ceftriaxone/metronidazole; 95% CI -13.3 to -0.6). The incidence of treatment-emergent adverse events was similar for both treatment groups (moxifloxacin 31.7% vs. comparator 24.3%). These results confirm previous findings that moxifloxacin plus adequate source control is an appropriate treatment of cIAI.

[Analysis of maltose clearance in plasma and urine of healthy volunteers with high-performance liquid chromatography].

OBJECTIVE: To analyze the maltose clearance in plasma and urine of healthy volunteers with high-performance liquid chromatography. METHODS: Maltose solution was infused to 12 healthy volunteers during a 4-hour period at an infusion rate of 0.2, 0.3, and 0.5 g/(kg x h), Plasma and urine specimens were collected at different time points before and after infusion, and then analyzed with high-performance liquid chromatography. RESULTS: The coefficients of variation of the precision and accuracy of the analysis method ranged 3.68%-4.58% and 0.44%-4.83% for plasma, respectively, and 2.91%-7.62% and 0.95%-8.27% for urine, respectively. The plasma maltose concentration increased in a dose-dependent manner (r > 0.99). The plasma maltose concentrations returned to the baseline levels 12 hours later. Two hours after injection, the urinary excretion of maltose increased, reached the peak value within 2-4 hours, began to decrease 6 hours later, and became zero 24 hours later. CONCLUSIONS: An infusion rate of 0.2-0.5 g/(kg x h) of maltose will not remarkably increase the blood glucose level in healthy people. The routine infusion rate should below 0.3 g/(kg x h), unless an emergency exists.

Microarray analysis of gene expression profile of multidrug resistance in pancreatic cancer.

BACKGROUND: Chemotherapy is the most frequently adopted adjuvant therapy of pancreatic ductal adenocarcinoma (PDAC), but the development of drug resistance reduces its effectiveness. Clarification of the mechanism of multidrug resistance (MDR) development in PDAC is needed to improve the therapeutic effect of chemotherapy. This study was aimed to investigate the molecular mechanism of MDR of PDAC and to identify genes associated with MDR development. METHODS: The gene expression profiles of cell line SW1990 and three drug-selected pancreatic chemoresistant sub-lines, SW1990/5-Fu, SW1990/ADM and SW1990/GEM, were obtained using an oligonucleotide microarray (Affymetrix HG U133 2.0 plus) that contained approximately 38,000 human genes. The microarray results were validated by real-time quantitative polymerase chain reaction and Western blot analysis. RESULTS: There were 165 genes and expressed sequence tags, some of which have never been linked to drug resistance, that were up- or down-regulated at least 2-fold in all resistant sub-lines when compared with SW1990. According to Gene Ontology annotation, differentially expressed genes related to MDR in pancreatic cancer belong to many functional families and with diverse biological processes. Genes related to antioxidant activity, apoptosis, the cell cycle, signal transduction and intracellular adhesion may undergo epigenetic changes preceding MDR development. A hierarchical clustering was conducted and several interesting clusters were discovered that may be primarily related to cell cycle and developmental regulation. A prediction rule was built from the expression profiles of 117 genes after support vector machine (SVM) analysis, and the prediction result was examined by cytotoxic testing. As a result, a differential gene expression pattern was constructed in multidrug resistant pancreatic cancer cells. CONCLUSIONS: The findings of this study prove that construction of a chemoresistance prediction rule, based on gene expression patterns, is practical. These data provide new insights into the molecular mechanism of pancreatic cancer MDR development and may be useful for the detection and treatment of MDR in pancreatic cancer patients.

[A randomized, double blind, and controlled clinical trial of the non-addictive propacetamol in postoperative analgesia].

OBJECTIVE: To compare the postoperative analgesic efficacy and safety of the non-addictive propacetamol hydrochloride (Pro-Bufferin) injection and dolantin in a prospective, randomized, double blind and controlled clinical trial. METHODS: After the pain intensity was assessed when the patients were undergone thoracic and abdominal selective surgery became fully conscious, 40 consecutive patients with moderate to severe postoperative pain (equivalent to Pain Grade I and II of American Anesthesia Association classification) were randomized into the study against the control groups. The two groups were similar for age, sex, height/weight, disease categories, operation categories, anesthesia methods and duration, vital signs, hepatorenal function, and blood cell count (P = 0.06-0.93). In the study group, 2 g propacetamol in 100 ml normal saline (NS) intravenously with 1.0 ml NS intramuscularly as the placebo control to dolantin were administered. In the control group, 1.6 g mannitose in 100 ml NS intravenously as the placebo control to propacetamol with 50 mg dolantin (1.0 ml) intramuscularly as the positive control to propacetamol were administered. The intensity change of postoperative pain was then evaluated 10 times with visual analog scale and verbal describing scale during 6 h from the beginning of propacetamol infusion. Vital signs and adverse reactions were also documented. After all data were put into the computer, the blinding codes were decoded and the statistic analysis was then made. RESULTS: There was no significant difference (P = 0.93) about the area under the curve of "Pain Relieve Score vs. Time". The "starting to effect" time (15-30 min), analgesic duration (6 h) and the percentage of excellent or good analgesic effect (90%) in the two groups were the same. Adverse reactions didn't reached the statistic different level (P = 0.35). CONCLUSIONS: Propacetamol HCL injection 2 g intravenously could be an alternative to dolantin 50 mg intramuscularly for moderate to severe postoperative pain with its advantage of being non-addictive.

The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial.

BACKGROUND: This research was conducted to evaluate the effect of enterally administered glutamine (gln) dipeptide on metabolic, gastrointestinal, and outcome parameters after severe burn injury. METHODS: Forty thermally injured patients with total body surface burns ranging between 50% and 80%, and third-degree burns ranging between 20% and 40% and without respiratory injuries, were randomized into a prospective, double-blind, controlled clinical trial. One group received gln-enriched enteral nutrition and the other group received the standard enteral formulation. Tube feedings were initiated on postburn day 1 (PBD +1), and isocaloric and isonitrogenous feedings were administered to both groups until PBD +12. The gln was given as the dipeptide of alanyl-gln (Ajinomoto, Tokyo, Japan), which provided 0.35 g gln/kg body weight/d. Plasma amino acid profiles, serum endotoxin concentrations, and the lactulose/mannitol absorption ratio (which reflects gut permeability) were measured at specific times throughout the clinical course. Wound healing at day 30 was assessed, and length of hospital stay and total costs were determined at discharge. RESULTS: The 2 groups were similar in terms of age and extent of injury. Plasma gln concentrations were approximately 300 umol/L in both groups on PBD +1 and remained low in the control group (399 +/- 40 umol/L, mean +/- SD) but increased toward normal in the supplemented group to 591 +/- 74 (p = .048). Lactulose/mannitol ratios were increased above normal on POD +1 (control, 0.221 +/- 0.169; gln, 0.268 +/- 0.202; not significant), reflecting increased intestinal permeability after burn injury. On POD +3, the ratio in the gln group was lower than control (0.025 +/- 0.008 versus 0.049 +/- 0.016; p = .0001), and both groups returned toward normal ratios with time. Endotoxin levels on PBD +1 were elevated in both groups (control, 0.089 +/- 0.023 EU/mL; gln, 0.103 +/- 0.037 EU/mL; NS) but decreased significantly on PBD +3 in the patients receiving gln. Hospital stay was significantly shorter in the gln group than controls (67 +/- 4 days versus 73 +/- 6; p = .026). On day 30, wound healing was 86% +/- 2% complete in the gln group compared with 72% +/- 3% in controls (p = .041). Total cost of hospitalization was 62794 +/- 6178 RMB (dollar 7593 +/- 747 US dollars) in the gln group and 68996 +/- 8620RMB (dollar 8343 +/- 1042, p = .031) in controls, although the cost of the enteral nutrition was higher in the gln-supplemented patients. CONCLUSION: Enteral gln supplementation using a commercially available dipeptide supported plasma gln levels, improved gut permeability, and initially decreased plasma endotoxin levels in severely thermally injured patients. These alterations were associated with a reduction in the length of hospitalization and lower costs.

[The role of nutritional status on serum immunoglobulins, body weight and postoperative infectious-related complications in patients with Crohn's disease receiving perioperative parenteral nutrition].

OBJECTIVE: To evaluate the role of nutritional status on serum immunoglobulins, body weight and postoperative infectious-related complications in patients with Crohn's disease receiving perioperative parenteral nutrition (PN). METHODS: 32 patients with Crohn's disease receiving perioperative parenteral nutrition in our department between 1984 and 1994 were enrolled in this survey. 16 patients with loss of body weight in the range of 15%-30% were assigned to the malnutrition group, the other 16 patients with normal weight or loss of body weight less than 15% to the control group. Serum IgM, IgG and IgA levels were measured before and after PN by enzyme-linked immunosorbent assays. Liver function, body weight changes and postoperative complications were also analyzed. RESULTS: IgM levels were elevated before PN in both groups [control group: (133 +/- 16) mg/dl, malnutrition group: (139 +/- 41) mg/dl; normal value: (110 +/- 35) mg/dl; P = 0.04], decreased to normal value [(105 +/- 29) mg/dl, P = 0.02] in the malnutrition group while having no obvious changes in the control group [(129 +/- 13) mg/dl, P = 0.34]. No significant changes in concentrations of IgG and IgA were found (P in the range of 0.20-0.57). The average weight gain was 1.862 kg in malnutrition group [before PN: (45.8 +/- 8.9) kg, after PN: (48.0 +/- 8.8) kg; P = 0.005] and no significant changes in the control group [before PN: (55.6 +/- 6.1) kg, after PN: (56.3 +/- 6.0) kg; P = 0.46]. There was an increase in infectious complications in the control group (control group: 4 cases, 25%, malnourished group: 2 cases, 12.5%; P = 0.13). CONCLUSIONS: Perioperative parenteral nutrition ameliorated the humoral immunity, increased the body weight in patients with obvious malnutrition, whereas it had little value for those without or with mild malnutrition.