Comparisons between diluted thrombin time, ecarin chromogenic assays, and UPLC-MS for plasma level dabigatran quantification: Results from DRIVING study.

INTRODUCTION: The knowledge of dabigatran levels is helpful for decision-making in specific situations such as urgent surgery or when the question of reversal arises (uncontrolled bleeding, eligibility for thrombolysis). However, a limited number of observational studies are available regarding comparisons between quantification methods. The objective of the study was to compare dabigatran plasma levels using three assays including the reference method (high-performance liquid chromatography coupled with mass spectrometry), focusing on the agreement around the 30-50 ng/mL clinically relevant thresholds. METHODS: Sixty healthy volunteers from DRIVING trial (NCT01627665) were given a single 300-mg dabigatran etexilate dose. Serial blood samplings were performed at pre-defined time points (0 to 24 h). We analyzed plasma samples using ultra-performance-liquid chromatography coupled with tandem mass spectrometry (UPLC-MS) (dabigatran reference method); ii/diluted thrombin time (dTT) (Hemoclot-DTI-Hyphen-Biomed); iii/ecarin-based chromogenic assay (ECA-II-Stago). RESULTS: Nine hundred sixty samples were analyzed using the three assays (2759 values). dTT and ECA-II values were highly correlated with those of UPLC-MS (Deming regression). Most values >50 ng/mL were higher using dTT and ECA-II compared to UPLC-MS: biases were constant, +14% and +16% with dTT and ECA-II, respectively (Bland-Altman plots), suggesting that active metabolites accounted for ~15% of thrombin inhibition. Regarding values <30 ng/mL, 30-50 ng/mL, or ≥50 ng/mL, the agreement probability between dTT and ECA-II was of 90.6% [88.4-92.5] (Cohen's kappa coefficient 0.84). CONCLUSION: dTT and ECA-II assays rapidly provide accurate dabigatran-level results for clinical practice, both assays being suitable in emergency, taking into account the thrombin inhibitory effect of dabigatran metabolites.

Factors Influencing Anti-Xa Assays: A Multicenter Prospective Study in Critically Ill and Noncritically Ill Patients Receiving Unfractionated Heparin.

BACKGROUND: The presence of dextran sulfate (DS) in reagents and the type of blood collection tube (citrate/citrated-theophylline-adenosine-dipyridamole [CTAD]) can lead to discrepancies between unfractionated heparin (UFH) anti-Xa levels. OBJECTIVES: To evaluate the extent of the effect (1) of different reagents containing or not containing DS and (2) of the blood collection tubes, on UFH anti-Xa levels, in various clinical situations (NCT04700670). METHODS: We prospectively included patients from eight centers: group (G)1, cardiopulmonary bypass (CPB) after heparin neutralization (n = 39); G2, cardiothoracic intensive care unit (ICU) after CPB (n = 35); G3, medical ICU (n = 53); G4, other medical inpatients (n = 38). Blood was collected into citrated and CTAD tubes. Chromogenic anti-Xa assays were centrally performed, using seven reagent/analyzer combinations including two without DS. The association between anti-Xa levels and covariates was tested using a linear mixed-effects model. RESULTS: We analyzed 4,546 anti-Xa values from 165 patients. Median anti-Xa levels were systematically higher with reagents containing DS, whatever the patient group, with the greatest effect observed in G1 (0.32 vs. 0.05 IU/mL). Anti-Xa levels were slightly higher in CTAD than in citrate samples, irrespective of the assay. The model showed: (1) a significant dextran-patient group interaction (p < 0.0001), the effect of DS on anti-Xa levels varying from 30.9% in G4 to 296% in G1, and (2) a significant effect of CTAD, varying between patient groups (p = 0.0302). CONCLUSION: The variability of anti-Xa levels with a great overestimation of the values, using a reagent containing DS, can lead to different treatment decisions, especially after heparin neutralization by protamine. Clinical consequences of these differences remain to be demonstrated.

Assessment of DOAC in GEriatrics (Adage Study): Rivaroxaban/Apixaban Concentrations and Thrombin Generation Profiles in NVAF Very Elderly Patients.

BACKGROUND: Although a growing number of very elderly patients with atrial fibrillation (AF), multiple conditions, and polypharmacy receive direct oral anticoagulants (DOACs), few studies specifically investigated both apixaban/rivaroxaban pharmacokinetics and pharmacodynamics in such patients. AIMS: To investigate: (1) DOAC concentration-time profiles; (2) thrombin generation (TG); and (3) clinical outcomes 6 months after inclusion in very elderly AF in-patients receiving rivaroxaban or apixaban. METHODS: Adage-NCT02464488 was an academic prospective exploratory multicenter study, enrolling AF in-patients aged ≥80 years, receiving DOAC for at least 4 days. Each patient had one to five blood samples at different time points over 20 days. DOAC concentrations were determined using chromogenic assays. TG was investigated using ST-Genesia (STG-ThromboScreen, STG-DrugScreen). RESULTS: We included 215 patients (women 71.1%, mean age: 87 ± 4 years), 104 rivaroxaban and 111 apixaban, and 79.5% receiving reduced-dose regimen. We observed important inter-individual variabilities (coefficient of variation) whatever the regimen, at C max [49-46%] and C min [75-61%] in 15 mg rivaroxaban and 2.5 mg apixaban patients, respectively. The dose regimen was associated with C max and C min plasma concentrations in apixaban (p = 0.0058 and p = 0.0222, respectively), but not in rivaroxaban samples (multivariate analysis). Moreover, substantial variability of thrombin peak height (STG-ThromboScreen) was noticed at a given plasma concentration for both xabans, suggesting an impact of the underlying coagulation status on TG in elderly in-patients. After 6-month follow-up, major bleeding/thromboembolic event/death rates were 6.7%/1.0%/17.3% in rivaroxaban and 5.4%/3.6%/18.9% in apixaban patients, respectively. CONCLUSION: Our study provides original data in very elderly patients receiving DOAC in a real-life setting, showing great inter-individual variability in plasma concentrations and TG parameters. Further research is needed to understand the potential clinical impact of these findings.

Clinical investigation of fertility after uterine artery embolization.

BACKGROUND: Uterine artery embolization is an effective and safe technique for the treatment of uterine fibroids, but its use remains controversial for women who wish to procreate. OBJECTIVE: This study aimed to study the clinical, anatomic, and obstetrical results of uterine artery embolization in patients of childbearing age not eligible for myomectomy. STUDY DESIGN: This was a retrospective cohort study of 398 female patients under the age of 43 years who were treated by uterine artery embolization between 2003 and 2017 for symptomatic fibroids and/or adenomyosis. Uterine artery embolization was performed according to a standardized procedure (fertility-sparing uterine artery embolization technique), with ovarian protection in the event of dangerous utero-ovarian anastomosis. Magnetic resonance imaging and pelvic ultrasounds were performed before and after uterine artery embolization. RESULTS: The overall clinical success rate (ie, resolution of preembolization symptoms such as heavy menstrual bleeding, iron-deficiency anemia, pelvic pressure) was 91.2%, and there were no major complications. One year after uterine artery embolization, we observed a mean 73% reduction in myoma volume. A total of 108 patients (49.3%) presented with dangerous utero-ovarian anastomosis and 33 (14.5%) benefited from ovarian protection. In our group, there were 148 pregnancies and 109 live births; 74 children were born at term; 23 were born preterm, on average at 35.12±2.78 weeks. Including preterm births, the mean birthweight and birth length of the children were within normal limits. Restoration of uterine anatomy and ovarian protection were identified as the main predictive factors for obstetrical success. Restoration was also a major predictive factor for clinical success and was associated with a lower rate of miscarriage. CONCLUSION: This study provided detailed clinical and obstetrical outcomes for 398 female patients who underwent uterine artery embolization for fibroid treatment; it contributes to the identification of anatomic and technical factors that could have an impact on fertility after uterine artery embolization. Further controlled clinical trials are needed to confirm our findings and reevaluate this procedure's indications and limitations for women with a desire to procreate.

Opioid epidemic: Does rheumatological practice favors risk for patients? National survey on rheumatologists' opioid prescriptions and compliance to guidelines for strong opioid prescription.

OBJECTIVES: Given the scope of rheumatology and its prevalence of pain, it seems needed that a study should focus on prescription habits, in the midst of the international opioid epidemic and given the moderate efficacy of strong opioids in chronic musculoskeletal conditions. We compared rheumatologists' opioid prescribing patterns in non-cancer pain with recommended practice. METHODS: We performed a cross-sectional study of the French health insurance database, including all patients aged 16 years or over reimbursed for at least one strong opioid prescription from a rheumatologist in 2015. A nationwide survey of all registered rheumatologists in France was performed with a 47-item questionnaire in June 2015. RESULTS: Only 2.4% of the patients receiving a strong opioid in 2015 (n=700,946) had at least one prescription from a rheumatologist. Rheumatologists prescribed mostly morphine, and significantly less oxycodone and fentanyl (P<0.00001) than other specialists. Rheumatologists prescribed a mean of 35.8mg morphine equivalent/day. A response rate of 33.7% was obtained to the questionnaire. Acute musculoskeletal pain was the principal condition for strong opioids prescription, with 94.5% re-evaluating opioid treatment within two weeks of initiation. For efficacy, 80% said that they stopped treatment if no benefit was observed after a test period (mean=1.2 months). Rheumatologists with pain management training were significantly more likely to evaluate pain before prescribing strong opioids (P=0.001), evaluate efficacy within three months (P=0.01) and screen for risk factors for misuse at initiation (P<0.0001). CONCLUSIONS: For non-cancer pain, rheumatologists generally prescribe opioids for short periods, at low doses, mostly according to national recommendations. Pain education strongly affected opioid prescription by rheumatologists.

Clustering with missing and left-censored data: A simulation study comparing multiple-imputation-based procedures.

Cluster analysis, commonly used to explore large biomedical datasets, can be challenging, notably due to missing data or left-censored data induced by the sensitivity limits of the biochemical measurement method. Usually, complete-case analysis, simple imputation, or stochastic simple imputation are applied before clustering. More recently, consensus methods following multiple imputation have been proposed. However, they ignore left-censoring and do not allow the number of clusters to vary across the partitions of each imputed dataset. Here, we developed a consensus-based clustering algorithm in which left-censored data are taken into account using a modified multiple imputation method and the number of clusters is estimated for each imputed dataset. A simulation study was conducted to assess the performance in terms of the number of clusters, the percentage of unclassified observations, and the adjusted Rand index. The simulation results showed that the investigated method works well compared to several alternative approaches. A real-world application in breast cancer patients showed that the proposed method may reveal novel clusters of patients.

Preserved efficiency of sickle cell disease placentas despite altered morphology and function.

INTRODUCTION: Pregnant women with sickle cell disease (SCD) are at high risk for sickle cell-related complications, obstetrical complications, and perinatal morbidity. Chronic inflammation and the proangiogenic environment associated with SCD have been associated with endothelial damage. It is unknown whether SCD complications could be associated with placental dysfunction or abnormal placental morphology. Moreover, circulating angiogenic factors in pregnant women with SCD are unexplored. METHODS: Clinical records, placental and blood samples were collected at term delivery for 21 pregnant patients with SCD and 19 HbAA pregnant controls with adapted to gestational age birth weight newborns. Histological and stereological analyses and scanning electron microscopy (SEM) of the placenta, and PlGF and sFlt1 measurements in blood were performed. RESULTS: In the SCD group, the parenchyma-forming villi of placentas were thinner than in controls, and increased fibrinoid necrosis and an overabundance of syncytial knots were seen. SEM revealed elongated intermediate villous endings with a reduction in the number of terminal villi compared to controls, indicating a significant branching defect in SCD placentas. Finally, SCD patients had an imbalance in the angiogenic ratio of sFlt1/PlGF (p = 0.008) with a drop of PlGF concentrations. DISCUSSION: We evidence for the first time both abnormal placenta morphology and altered sFlt1/PlGF ratio in SCD patients, uncorrelated with maintained placental efficiency and fetal growth.

Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites.

Despite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to graft versus host disease (GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment or host microbiota. Here we used high throughput metabolomics to analyze two cohorts of genotypically HLA-identical related recipient and donor pairs. Metabolomic profiles markedly differ between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identify significant variation in microbiota-derived metabolites, especially in aryl hydrocarbon receptor (AhR) ligands, bile acids and plasmalogens. Altogether, our findings support that the allogeneic immune response during acute GvHD might be influenced by bile acids and by the decreased production of AhR ligands by microbiota that could limit indoleamine 2,3-dioxygenase induction and influence allogeneic T cell reactivity.

Lean Body Mass and Endocrine Status But Not Age Are Determinants of Resting Energy Expenditure in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: Cancer and aging are both frequently associated with malnutrition, a factor of poor prognosis. In adult cancer patients, this may be related in part to impaired energy metabolism, with higher than predicted resting energy expenditure (REE) in about 50% of patients. We hypothesized that frequently impaired energy metabolism in elderly patients could potentiate cancer-associated hypermetabolism, further promoting risk of malnutrition. OBJECTIVE: To study the hypermetabolic response to cancer in a predominantly aged population and the potential underlying determinants. METHODS: This was a cross-sectional exploratory study in patients with non-small-cell lung cancer. REE was measured by indirect calorimetry. Body composition was determined from a single CT scan imaging at L3 level. Endocrine, inflammatory, nutritional and metabolic status were evaluated. RESULTS: Twenty-seven patients, of median age 68 years (range 32-81) completed the study. In this population, mean measured REE was 7.5% higher than calculated REE. Sex and weight accounted for about 51% of REE variations, whereas age accounted only for 4%. However, these parameters did not explain the REE-to-lean body mass (LBM) ratio variations, suggesting that they influenced REE only through their effect on LBM. Among the other parameters evaluated, only the thyroid-stimulating hormone and interleukin-6 plasma levels appeared to have an influence on REE. The study of the consequences of this increase in REE-to-LBM ratio showed a growing inability of patients to meet their energy needs but showed no effect on nutritional markers such as transthyretin. CONCLUSIONS: The results of this pilot study suggest that in our population, age was not an important factor of REE. The elevated energy metabolism was associated with patients' failure to increase their energy intakes sufficiently, which can contribute to the development of cachexia. CLINICAL TRIAL: This trial is registered at clinicaltrials.gov under NCT0314.

Pain assessment and factors influencing pain during bone marrow aspiration: A prospective study.

Although bone marrow aspiration (BMA) is still considered a painful procedure, pain level remains poorly documented. We therefore conducted a prospective study intended to evaluate pain level in adult patients undergoing BMA at the sternal or iliac crest site to identify factors associated with pain. We enrolled a total of 448 patients who underwent 461 BMA and asked those patients to score their pain intensity after BMA using numerical pain rating scale (NPRS). The following factors: level of anxiety, quality of the information given to the patient, operator's experience, and bone texture were recorded using a standardized questionnaire. The median NPRS score was 3.5 (IQR [2.0; 5.0]) the sternal site (n = 405) was associated with an increased median NPRS score (3.5 [2.0; 5.0]) compared to the iliac crest (n = 56, 2.5 [1.0; 4.0]; p<0.0001). For those patients who underwent sternal BMA, the median NPRS score was significantly lower when using lidocaine infiltration (p = 0.0159) as compared with no anesthetic use. Additionally there was no significant effect of anesthetic cream found. After multivariate analysis, the model of NPRS score at the sternal site included patient anxiety (p<0.0001) and the use of lidocaine infiltration (0.0378). This study underlines the usefulness of a comprehensive management including pain relief and efforts to reduce anxiety including appropriate information given to the patient during BMA.

CD34+ Hematopoietic Stem Cell Count Is Predictive of Vascular Event Occurrence in Children with Sickle Cell Disease.

BACKGROUND/OBJECTIVES: Sickle cell disease (SCD) complications mostly result from vascular dysfunction, concerning systemic microvasculature and cerebral large vessels. The aim of this cohort study was to identify potential circulating biomarkers predictive for further vascular event occurrence in pediatric SCD. METHODS: We consecutively enrolled 108 children with SCD at steady state, aged 3-18 years old (median 9.8 years). Hematology, coagulation, hemolysis, endothelial, platelet and vascular activation parameters were recorded at inclusion. Neurovascular and systemic vascular events were prospectively recorded during a mean follow-up period of 27 months. RESULTS: Patients at steady state displayed significantly higher hemolysis and platelet activation markers, higher leukocyte, CD34+ hematopoietic stem cell and microvesicle counts, and a pro-coagulant profile compared to controls matched for age and ethnicity. Circulating endothelial cell or nucleosome level did not differ. During the follow-up period, 36 patients had at least one neurovascular (n = 12) or systemic vascular event (n = 25). In a multivariate model, high CD34+ cell count was the best predictor for the occurrence of a vascular event (OR 1.2 for 1000 cell/mL increase, 95% CI [1.049-1.4], p = 0.013, sensitivity 53%, specificity 84% for a threshold of 8675 cells/mL). CONCLUSION: CD34+ cell count at steady state is a promising biomarker of further vascular event in children with SCD.

Nitric oxide production by peritoneal macrophages from aged rats: A short term and direct modulation by citrulline.

Citrulline has anti-inflammatory properties and exerts beneficial effects on various impaired functions in aging. However, there are few data on citrulline action on immune function in aged populations. The objective of the study was to evaluate citrulline ability, after in vivo and in vitro administration, to modulate macrophage functions in aged rats and the possible pathways involved. Twenty-one-month-old Sprague-Dawley rats (n = 27) received a citrulline supplementation at 5 g/kg/d for 5 days, or an isonitrogenous diet, and peritoneal macrophages were cultured with or without LPS. In the in vitro study, macrophages from 22-month-old rats (n = 16) were cultured with or without LPS, citrulline and inhibitors of different inflammatory pathways (n = 8/conditions). Nitric oxide (NO) and tumor necrosis factor α (TNFα) production were measured in both in vivo and in vitro studies. Citrulline decreased NO production variability by peritoneal macrophages after in vivo administration (p = 0.0034) and downregulated NO production by 22% after in vitro administration (95% CI: [6%; 35%]; p = 0.0394), without any direct effect on TNFα production. None of the transductional pathways explored seem to be involved. Citrulline slightly modulates NO production in vivo and in vitro, suggesting a possible action through modulation of arginine metabolism in macrophages rather than a direct transductional effect. The pleiotropic effects of citrulline in aging could be due, at least in part, to the anti-inflammatory effect of citrulline.

Anastomotic leakage after colorectal surgery: diagnostic accuracy of CT.

OBJECTIVES: To evaluate the diagnostic accuracy of CT in postoperative colorectal anastomotic leakage (AL). METHODS: Two independent blinded radiologists reviewed 153 CTs performed for suspected AL within 60 days after surgery in 131 consecutive patients, with (n = 58) or without (n = 95) retrograde contrast enema (RCE). Results were compared to original interpretations. The reference standard was reoperation or consensus (a radiologist and a surgeon) regarding clinical, laboratory, radiological, and follow-up data after medical treatment. RESULTS: AL was confirmed in 34/131 patients. For the two reviewers and original interpretation, sensitivity of CT was 82 %, 87 %, and 71 %, respectively; specificity was 84 %, 84 %, and 92 %. RCE significantly increased the positive predictive value (from 40 % to 88 %, P = 0.0009; 41 % to 92 %, P = 0.0016; and 40 % to 100 %, P = 0.0006). Contrast extravasation was the most sensitive (reviewers, 83 % and 83 %) and specific (97 % and 97 %) sign and was significantly associated with AL by univariate analysis (P < 0.0001 and P < 0.0001). By multivariate analysis with recursive partitioning, CT with RCE was accurate to confirm or rule out AL with contrast extravasation. CONCLUSIONS: CT with RCE is accurate for diagnosing postoperative colorectal AL. Contrast extravasation is the most reliable sign. RCE should be performed during CT for suspected AL. KEY POINTS: • CT accurately diagnosed clinically suspected colorectal AL and showed good interobserver agreement • Contrast extravasation was the most sensitive and specific CT sign • Retrograde contrast enema during CT improved positive predictive value • Retrograde contrast enema decreased false-negative or indeterminate original CT interpretations.

Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections.

PURPOSE: Clindamycin, a lincosamide antibiotic with a good penetration into bone, is widely used for treating bone and joint infections by Gram-positive pathogens. To be active against Staphylococcus spp, its concentration at the infection site, C, must be higher than 2× the minimal inhibitory concentration (MIC). The aims of the work were to study the determinants of plasma clindamycin trough concentration, C min, especially the effect of co-treatment with rifampicin, and the consequences on clinical outcome. METHODS: An observational study was performed, involving patients hospitalized for a bone and joint infection who received clindamycin as part of their antibiotic treatment. Target C min was 1.7 mg/L, to reach the desired bone concentration/MIC >2, assuming a 30% diffusion into bone and MIC = 2.5 mg/L. RESULTS: Sixty one patients (mean age: 56.8 years, 57.4% male) were included between 2007 and 2011. 72.1% underwent a surgery on a foreign material, and 91.1% were infected by at least a Gram-positive micro-organism. Median C min value was 1.39 mg/L, with 58% of the values below the threshold value of 1.7 mg/L. Median C min was significantly lower for patients taking rifampicin (0.46 vs 1.52 mg/L, p = 0.034). No patient with rifampicin co-administration reached the target concentration (maximal C min: 0.85 mg/L). After a median follow-up of 17 months (1.5-38 months), 4 patients relapsed, 2 died and 47 (88.7% of the patients with known outcome) were cured, independently of association with rifampicin. CONCLUSIONS: This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.

KCNH2 polymorphism and methadone dosage interact to enhance QT duration.

BACKGROUND: Many drugs increase the duration of the QT interval of patients, potentially leading to harmful effects such as polymorphic ventricular arrhythmias. Most of these drugs do so by inhibiting the rapid component IKr of the delayed rectifier potassium current IK. Methadone is the most prescribed heroin maintenance treatment and is known to inhibit the cardiac potassium channel hERG, which recapitulates IKr. In order to evaluate if any polymorphism of potassium channels' genes could explain some of the "idiosyncratic" QT prolongations observed in patients treated with methadone, we tested the association between KCNE1, KCNE2, and KCNH2 polymorphism and the QT interval prolongation in those patients, controlling for other variables associated with a decrease of the repolarizing reserve. METHODS: A cohort of 82 patients treated with stable dosage of methadone (mean dosage 65 mg/d) for at least three months was genotyped for five polymorphisms in KCNE1, KCNE2 and KCNH2 genes and had their corrected QT (QTc) assessed. RESULTS: The mean QTc interval was 415±34ms. In a linear regression model, longer QTc interval was associated with methadone dosage and with one genetic factor. Each copy of a Lys allele at codon 897 of KCNH2, the gene that encodes the cardiac potassium voltage-gated channel hERG, was associated with a 15.4ms longer QTc (95% CI [4.6-26.2]; p=0.001). CONCLUSION: KCNH2 genotyping may be relevant in the analysis of cumulative risk factors for QT prolongation in patients on methadone maintenance treatment.

Incidence of pulmonary cement embolism after real-time CT fluoroscopy-guided vertebroplasty.

PURPOSE: To prospectively evaluate the incidence of pulmonary cement embolism (PCE) after vertebroplasty in procedures performed under real-time computed tomographic (CT) fluoroscopy guidance. MATERIALS AND METHODS: A total of 85 vertebroplasties were performed in 51 consecutive patients (31 women, 20 men; mean age, 71.9 y; range, 48-92 y) in 51 sessions. The needle was inserted with guidance from intermittent single-shot CT scans, and intermittent CT fluoroscopy was used during cement injection only. To reduce the risk of extravertebral or extraosseous leakage, several procedures (cement injection stopping/slowing, needle position changes) were employed. The chest and treated bone were scanned immediately after vertebroplasty. These CT images included the entire thorax as well as the treated vertebrae. RESULTS: No cement emboli were observed on CT after vertebroplasty. After 85 vertebroplasty procedures, 44 extravertebral leaks were detected. Epidural leaks were observed on CT in six treated vertebrae (7%), in 12 cases in the anterior external venous plexus (14.1%), in five in the azygos vein (5.8%), in 19 in the disc space (22%), and in two in the foraminal space (2.3%). On a per-patient basis, the odds of leaks increased with the number of vertebroplasties (P = .05) and the volume of cement used (P = .0412). There was also a higher probability of leak (P < .05) for osteoporotic vertebral compression fractures (67.9%; 95% confidence interval, 47.7%-84.1%) than osteolytic spinal metastases (34.8%; 16.4%-57.3%). CONCLUSIONS: PCE did not occur after vertebroplasty under CT fluoroscopy guidance. Further larger prospective vertebroplasty studies are needed to compare the rates of PCE for CT versus conventional fluoroscopic guidance.

Peripherally inserted central catheter placement in cancer patients with profound thrombocytopaenia: a prospective analysis.

OBJECTIVE: No studies have specifically evaluated the safety of peripherally inserted central catheter (PICC) placement in patients with profound thrombocytopaenia. We prospectively determined the frequency of haemorrhagic complications of PICC placement in cancer patients with uncorrected profound thrombocytopaenia. METHODS: Profound thrombocytopaenia was defined as a platelet count <50 × 10(9)/l. No patients received transfusions before or after the procedure. Three types of adverse effects were analysed: minor oozing, mild haematoma and major haemorrhage. RESULTS: One hundred and forty-three PICC implantations in 101 cancer patients were prospectively included in the study: seven patients (7 %) had a solid tumour and 94 (93 %) a haematological malignancy. Among these 143 procedures in thrombocytopaenic patients, 93 (65 %) were performed with a platelet count 20-50 × 10(9)/l and 50 (35 %) had lower than 20 × 10(9)/l. No major haemorrhage was observed. Minor oozing was observed in six implantations (4 %) and mild haematoma in two (1.5 %), for a total of eight minor haemorrhagic adverse events (5.5 %). In patients with a platelet count <20 × 10(9)/l, 1/50 (2 %) had minor oozing and none had minor haematoma. CONCLUSIONS: In cancer patients with uncorrected profound thrombocytopaenia, the incidence of adverse events after PICC implantation was low, and was limited to minor haemorrhagic adverse events. KEY POINTS: • PICC placement has high technical success in profound thrombocytopaenic cancer patients. • Few adverse events are encountered after PICC placement, limited to minor haemorrhage. • PICC placement does not routinely require platelet transfusion in patients with thrombocytopaenia. • Such PICC placement still seems safe when the platelet count is <20 × 10 (9) /l.

TNF-α/IL-2 ratio discriminates latent from active tuberculosis in immunocompetent children: a pilot study.

BACKGROUND: Distinguishing latent tuberculosis (LTB) from tuberculosis (TB) disease may be challenging in children. Here, we analyzed cytokine profiles that can distinguish the two infection stages in a nonendemic country (France). METHODS: Immunocompetent children with LTB (n = 6) or TB disease (n = 8) (median age: 6.2 and 5.7 years, respectively) were analyzed. Four young uninfected children were included as controls. A Luminex assay evaluated cytokine responses to Mycobacterium tuberculosis antigens. RESULTS: Poor interleukin-4 (IL-4) and IL-10 responses precluded analysis of these cytokines. Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-2, and T-helper type 1 (Th1) cytokines and IL-5, IL-13, T-helper type 2 (Th2) cytokines were simultaneously induced by antigens in 14/14 infected but 0/4 uninfected children. Th1 cytokine levels were similar in LTB and TB disease: IFN-γ: 12,254 and 10,495 pg/ml; IL-2: 2,097 and 1,869 pg/ml; and TNF-α: 1,020 and 2,875 pg/ml, respectively. Th2 cytokine levels were similar and even higher in LTB than in TB disease: IL-5: 23 and 10 pg/ml; IL-13: 284 and 109 pg/ml, respectively. Positive correlation of cytokine levels, whether Th1 or Th2, was observed. Higher (P = 0.008) TNF-α/IL-2 ratios distinguished 6/8 active TB disease cases from 6/6 LTB cases. CONCLUSION: TNF-α/IL-2 ratio may discriminate TB disease from LTB in immunocompetent children. Larger studies in TB endemic settings must verify these results.

Effects of a diabetes-specific enteral nutrition on nutritional and immune status of diabetic, obese, and endotoxemic rats: interest of a graded arginine supply.

OBJECTIVE: Obese and type 2 diabetic patients present metabolic disturbance-related alterations in nonspecific immunity, to which the decrease in their plasma arginine contributes. Although diabetes-specific formulas have been developed, they have never been tested in the context of an acute infectious situation as can be seen in intensive care unit patients. Our aim was to investigate the effects of a diabetes-specific diet enriched or not with arginine in a model of infectious stress in a diabetes and obesity situation. As a large intake of arginine may be deleterious, this amino acid was given in graded fashion. DESIGN: Randomized, controlled experimental study. SETTING: University research laboratory. SUBJECTS: Zucker diabetic fatty rats. INTERVENTIONS: Gastrostomized Zucker diabetic fatty rats were submitted to intraperitoneal lipopolysaccharide administration and fed for 7 days with either a diabetes-specific enteral nutrition without (G group, n=7) or with graded arginine supply (1-5 g/kg/day) (GA group, n=7) or a standard enteral nutrition (HP group, n=10). MEASUREMENTS AND MAIN RESULTS: Survival rate was better in G and GA groups than in the HP group. On day 7, plasma insulin to glucose ratio tended to be lower in the same G and GA groups. Macrophage tumor necrosis factor-α (G: 5.0±1.1 ng/2×106 cells·hr⁻¹; GA: 3.7±0.8 ng/2×106 cells·hr⁻¹; and HP: 1.7±0.6 ng/2×106 cells·hr⁻¹; p<.05 G vs. HP) and nitric oxide (G: 4.5±1.1 ng/2×106 cells·hr⁻¹; GA: 5.1±1.0 ng/2×106 cells·hr⁻¹; and HP: 1.0±0.5 nmol/2×106 cells·hr⁻¹; p<.05 G and GA vs. HP) productions were higher in the G and GA groups compared to the HP group. Macrophages from the G and GA groups exhibited increased arginine consumption. CONCLUSIONS: In diabetic obese and endotoxemic rats, a diabetes-specific formula leads to a lower mortality, a decreased insulin resistance, and an improvement in peritoneal macrophage function. Arginine supplementation has no additional effect. These data support the use of such disease-specific diets in critically ill diabetic and obese patients.