Comparison of ultrasound-guided versus fluoroscopy-guided reduction of forearm fractures in children.

PURPOSE: Point-of-care ultrasound (POCUS) can be used to guide and assess reduction of pediatric forearm fractures. In this study, we sought to compare the success rate of ultrasound-guided fracture reduction with fluoroscopy-guided fracture reduction. We also sought to determine whether there are cost or time benefits to using ultrasound instead of fluoroscopy. METHODS: The electronic medical records of patients less than 18 years of age presenting to a pediatric emergency department with a forearm fracture between April 2016 and March 2019 were screened for inclusion in this study. A total of 27 ultrasound-guided reductions were identified during this time period and 81 fluoroscopy-guided reductions were randomly selected for comparison. Cost data was provided by the financial department. Reduction success, total length of stay, and costs were compared between the two groups, and multiple linear regression was used to determine the influence of any confounding predictor variables. RESULTS: There were no failed reductions in either group. Length of stay was shorter in the POCUS group (221 min) compared with the fluoroscopy group (254 min, p = 0.014), but this significance was lost in the regression model when adjusted for ketamine use. Provider costs ($430 v $442, p = 0.822) and total costs ($1219 v $1204, p = 0.851) were the same between the POCUS group and the fluoroscopy group, respectively. CONCLUSION: POCUS appears to be an equally effective imaging modality to guide reduction of forearm fractures as compared to fluoroscopy.

Prospective Investigation of a Novel Ultrasound-assisted Lumbar Puncture Technique on Infants in the Pediatric Emergency Department.

OBJECTIVE: The objective was to describe a novel ultrasound-assisted lumbar puncture (UALP) technique and to compare it to standard lumbar puncture (SLP) technique in infants. METHODS: A prospective, randomized, controlled study in infants 60 days old and younger undergoing a lumbar puncture (LP) in a pediatric emergency department. Patients with a spinal anomaly or ventriculoperitoneal shunt were excluded. Eligible infants were randomized to UALP or SLP. A spinal sonogram was performed on all patients by an investigator not involved in performing the LP. Spinal landmarks and maximum safe depth were identified for the UALP providers. Providers in the SLP group were blinded to sonographic measurements. A successful LP was defined as the collection of cerebrospinal fluid (CSF) with a red blood cell count of less than 10,000 cells/mm3 . Statistical analysis included chi-square, Mann-Whitney U-test, and number needed to treat (NNT). RESULTS: Forty-three patients were enrolled, 21 in the UALP group and 22 in the SLP group. Prematurity, weight, length, provider experience, anesthesia use, stylet technique, and number of attempts were similar between groups. The median age in the UALP group was 38 days (interquartile range [IQR] = 33 days) versus 45 days (IQR = 19 days) in the SLP group (p = 0.02). CSF was obtained in all UALP subjects (100%) versus in 18 of 22 (82%) in the SLP group (p = 0.04); 20 (95%) UALP subjects versus 15 (68%) SLP subjects met our definition of success (p = 0.023). The odds ratio of successful LP using UALP technique was 9.33 (95% confidence interval [CI] = 1.034 to 84.026) and the NNT was 3.7 (95% CI = 2.02 to 24.18). CONCLUSION: The UALP technique increases the rate of a successful LP in infants compared to standard technique.

A pilot study of docetaxel and trofosfamide as second-line 'metronomic' chemotherapy in the treatment of metastatic non-small cell lung cancer (NSCLC).

BACKGROUND: The aim of this pilot study was to evaluate the efficacy and safety of a chemotherapy containing docetaxel and oral trofosfamide as a 'metronomic' secondline treatment of patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: 21 patients with stage IV disease NSCLC who had progressed under first-line chemotherapy were enrolled. Previous chemotherapy was platinum-based in 15 patients (71.4%), whereas 6 patients (28.6%) had received platinum-free combination chemotherapy. Patients received docetaxel 25 mg/m(2) on days 1, 8, and 15 every 4 weeks plus trofosfamide 50 mg per day. RESULTS: A total of 62 chemotherapy cycles were administered. The median number of cycles per patient was 3. The overall response rate to chemotherapy was 19%, median overall survival was 6.9 months, the median progression-free survival 2.9 months, the 1-year survival rate 28.6%, and the 2-year survival rate 7.1%. No grade IV toxicity was observed. CONCLUSIONS: Our results suggest that the combination of docetaxel and trofosfamide in a metronomic schedule is active and well tolerable as second-line therapy in patients with metastatic NSCLC. The concept of metronomic chemotherapy promises to be a valuable addition to the existing treatment options in NSCLC and warrants further investigation in phase III studies.

Intraosseous infusion: a review of methods and novel devices.

This is a review article of intraosseous infusion methods and devices.

ATP and cytochrome c-dependent activation of caspase-9 during hypoxia in the cerebral cortex of newborn piglets.

In previous studies, we have shown that cerebral hypoxia results in increased activity of caspase-9, the initiator caspase, and caspase-3, in the cytosolic fraction of the cerebral cortex of newborn piglets. The present study examines the mechanism of caspase-9 activation during hypoxia and tests the hypothesis that the ATP and cytochrome c-dependent activation of caspase-9 increases in the cytosol of the cerebral cortex of newborn piglets. Newborn piglets were divided into normoxic (Nx, n=4), and hypoxic (Hx, n=4) groups. Anesthetized, ventilated animals were exposed to an FiO(2) of 0.21 (Nx) or 0.07 (Hx) for 60 min. Cerebral tissue hypoxia was documented biochemically by determining levels of ATP and phosphocreatine (PCr). Cytosolic fraction was isolated and passed through a G25-Sephadex column to remove endogenous ATP and cytochrome c. Fractions were collected and protein determined by UV spectrophotometry at 280 nm. Eluted high-molecular weight samples from normoxic and hypoxic animals were divided into four subgroups: subgroup 1 (control), incubated without added ATP and cytochrome c; subgroup 2, incubated with added ATP; subgroup 3, incubated with added cytochrome c; and subgroup 4, incubated with added ATP and cytochrome c. The incubation was carried out at 37 degrees C for 30 min. Following incubation, the protein was separated by 12% SDS-PAGE and active caspase-9 was detected using specific active caspase-9 antibody. Protein bands were detected by enhanced chemiluminescence. Protein density was determined by imaging densitometry and expressed as absorbance (OD x mm(2)). ATP (mumol/g brain) level was 4.7 +/- 0.18 in normoxic, as compared to 1.53 +/- 0.16 in hypoxic (p < 0.05 vs. Nx). PCr (mumol/g brain) level was 4.03 +/- 0.11 in the normoxic and 1.1 +/- 0.3 in the hypoxic brain (p < 0.05 vs. Nx). In the normoxic preparations, active caspase-9 density increased by 9, 4 and 20% in the presence of ATP, cytochrome c and ATP+cytochrome c, respectively. In the hypoxic preparations, active caspase-9 density increased by 30, 45 and 60% in the presence of ATP, cytochrome c and ATP+cytochrome c, respectively. These results show that incubation with ATP, cytochrome c and ATP+cytochrome c result in a significantly increased activation of caspase-9 in the hypoxic group (p < 0.05). We conclude that the ATP and cytochrome c dependent activation of caspase-9 is increased during hypoxia. We propose that the ATP and cytochrome c sites of apoptotic protease activating factor I that mediate caspase-9 activation are modified during hypoxia.

A phase II study of irinotecan (CPT-11) and carboplatin in patients with limited disease small cell lung cancer (SCLC).

PURPOSE: The aim of this phase II trial was to evaluate the efficacy and safety of a combination chemotherapy containing irinotecan (CPT-11) and carboplatin as first-line treatment of patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: From December 2002 to May 2004 61 patients with limited disease (IASLC classification) were enrolled who were not suitable for concurrent chemo-radiotherapy. Eighteen of the 61 patients (29.5%) had malignant pleural or pericardial effusion and 4 patients (6.6%) had involved supra- or infraclavicular lymph nodes. Patients received irinotecan 50mg/m(2) on days 1, 8 and 15 and carboplatin AUC 5 on day 1, every 4 weeks. RESULTS: A total of 233 chemotherapy cycles were administered. The median number of cycles per patient was 4. The overall response rate to chemotherapy on an intention-to-treat basis was 64%. The median overall survival was 13.8 months, the median disease-free survival 8.0 months, the 1-year survival rate 53.5%, and the 2-year survival rate 17.9%. Haematological and non-hematogical toxicities were low (CTC-grade 3 neutropenia 14.8%, grade 3 thrombocytopenia 5.2%, grade 3/4 anemia 5.1%, grade 3 nausea/vomiting 5.1%, grade 3 diarrhea 3.6%, grade 3 alopecia 3.6% of pts). CONCLUSION: The results suggest that the combination of irinotecan (CPT-11) and carboplatin is active and well tolerable in patients with limited disease SCLC who were not suitable for concurrent chemotherapy.

Docetaxel and cisplatin as first-line treatment for patients with metastatic esophageal cancer: a pilot study.

BACKGROUND: We investigated the combination of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic esophageal cancer. PATIENTS AND METHODS: 16 chemotherapy-naïve patients with distant metastases were included in the study (15 male, 1 female; median age: 58.5 years (range 37-69); median ECOG performance status: 1). 11 patients (69%) had esophageal cancer, and 5 patients (31%) had cancer of the gastroesophageal junction. Patients received docetaxel 75 mg/m2 and cisplatin 80 mg/m2 on day 1 every 3 weeks. A total of 55 chemotherapy cycles was administered. The median number of cycles was 3 (range 1-6). RESULTS: The overall response rate was 31.3%. 4 out of 10 patients (40%) with squamous cell carcinoma and 1 out of 5 patients (20%) with adenocarcinoma responded to chemotherapy. The median overall survival was 29.6 weeks, and the median progression-free survival was 18.6 weeks. Hematological and non-hematological toxicities were moderate (neutropenia WHO grade III/IV: 42.9%, alopecia grade II/III: 64.3%, nausea/vomiting grade II/III: 57.2%, neurotoxicity grade II: 14.3%). CONCLUSION: The combination of docetaxel and cisplatin is an active regimen with moderate toxicity in the treatment of patients with metastatic esophageal cancer. This pilot study demonstrates the feasibility of a combination treatment containing a taxane and cisplatin in metastatic esophageal cancer.

Pretreatment vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) serum levels in patients with metastatic non-small cell lung cancer (NSCLC).

PURPOSE: In the present study, we investigated the prognostic value of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 serum levels in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From September 1999 to June 2001, pretreatment serum levels of VEGF and MMP-9 were analysed in 194 patients of a randomized phase III trial with enzyme-linked immunoassays. RESULTS: Patients with a VEGF serum level higher than the median serum level (10,995 pg/ml) had a significantly shorter overall survival than those with a lower serum level (P=0.04). The MMP-9 serum level did not correlate with survival. In a multivariate Cox regression analysis, only the pretreatment serum level of VEGF, the Karnofsky performance status, and the presence of bone metastases were identified as independent prognostic factors. CONCLUSIONS: The pretreatment VEGF serum level was identified as independent prognostic factor in this study and may help to assess individual risk and treatment profiles in patients with metastatic NSCLC.

Serum levels of Magic Roundabout protein in patients with advanced non-small cell lung cancer (NSCLC).

BACKGROUND: Magic Roundabout (MR; ROBO 4) is a recently discovered gene which encodes a protein that derived its name form the structural homology with the roundabout family of genes. Genes of the roundabout family comprise neuronal-specific cell surface receptors that are involved in axon guidance. MR in contrast showed endothelial specificity in vitro and in vivo using immunohistochemistry and in situ hybridisation. The putative role of MR as an endothelial analogue of Roundabout in angiogenesis makes it an attractive target for anti-angiogenic cancer therapy. PATIENTS AND METHODS: Using specific antibodies against MR peptide, we screened pretreatment sera from 193 patients with advanced non-small cell lung cancer (NSCLC) for MR-protein levels. RESULTS: Patients with serum levels of MR-protein lower than median (E(450 nm) = 0.652) had a median survival of 41.0 weeks whereas those with a higher serum level had a considerably shorter median survival of 32.4 weeks (P = 0.05). The pretreatment serum level of MR-protein achieved no significance in a univariate Cox regression analysis. CONCLUSIONS: This is the first study to present clinical data that link MR expression with outcome in patients with NSCLC, whether the correlation of pretreatment serum levels of MR and survival can be attributed to MR dependent angiogenesis remains to be investigated.

Magic roundabout is a new member of the roundabout receptor family that is endothelial specific and expressed at sites of active angiogenesis.

We have used bioinformatic data mining to identify a novel, endothelial-specific gene encoding a protein with homology to the axon guidance protein roundabout (ROBO1). The new gene has been called magic roundabout (ROBO4; GenBank acc. no. AF361473) and is smaller than other members of the roundabout gene family. Thus, in the extracellular region, magic roundabout has only two of the five immunoglobulin and two of the three fibronectin domains present in other roundabout genes. Expression of magic roundabout in vitro was detected in only endothelial cells and was greater in cells exposed to hypoxia. In situ hybridization and immunohistochemistry validated the bioinformatic prediction that magic roundabout expression would be endothelial specific in vivo. Magic roundabout expression in the adult was restricted exclusively to sites of active angiogenesis, notably tumor vessels. The identification of magic roundabout shows that the roundabout gene family extends beyond neuronal tissue and that roundabout/slit interactions are likely to have a role in angiogenesis.