Complete resection of early-stage non-small cell lung cancer (NSCLC) is potentially curative, yet approximately 50% of patients are at risk for developing metastatic recurrence. Met, the receptor for ...hepatocyte growth factor (HGF) is a receptor tyrosine kinase with demonstrated roles in regulating cellular proliferation, motility, morphogenesis, and apoptosis. Met receptor and its ligand, HGF, are commonly overexpressed in NSCLC, and their overexpression has been associated with poor prognosis, which could potentially involve a paracrine and/or autocrine activation loop. However, there is as yet no direct evidence that HGF-Met signaling directly promotes metastasis in NSCLC cells. Using retroviral transduction, we overexpressed the human c-met and hgf complementary DNA, alone or in combination in the NCI-H460 human large cell carcinoma cell line. The HGF/Met co-overexpressing (H460-HGF/Met) cells demonstrated enhanced tumorigenicity in xenograft SCID mice. When these cells are implanted orthotopically into the lungs of nude rats, only the H460-HGF/Met cells showed higher spontaneous metastases to distant organs including bone, brain, and kidney. These results provide evidence that autocrine overactivation of the Met- HGF loop enhances systemic metastases in NSCLC. Targeted interference of this loop may potentially be an effective adjuvant therapy to improve survival of early-stage NSCLC patients.
To evaluate the performance of the StatStrip™ glucose meter from Nova Biomedical for use in complex tertiary care facilities.
Performance evaluation was conducted in 6 clinical locations involving ...nurse end-users. Imprecision (CV)
<
5% was considered acceptable. Ten substances were examined for potential analytical interferences at two levels and 3 glucose concentrations. Inaccuracy was determined by 386 paired glucose differences between glucose meter and laboratory reference analyses. Acceptability was based on CSLI/ISO15197 criteria. Potential clinical impact was classified under a 5-level severity scheme.
Imprecision varied from CV 2.4 to 4.9%. Significant interference was observed only for free hemoglobin at 10 g/L. 97% of paired glucose meter-laboratory differences met CSLI/ISO15197 criteria. All discrepant results had low severity scores.
The StatStrip™ glucose meter demonstrated acceptable imprecision and inaccuracy, and was relatively free from common interferences. It should be a good candidate for general use in complex tertiary care facilities.
Tetrabromphenol blue dye based methods are used to detect proteinuria using urinalysis dipsticks. Manufacturers have claimed that alkalinity leads to false positive proteinuria, and that high ...specific gravity leads to false negative protein results. However, published reports describing this phenomenon remain equivocal. This study aimed to determine whether pH and/or specific gravity affect protein detection in patient urine using three different tetrabromophenol blue dye-based dipsticks.
Patient urine pools were divided into individual aliquots with varied pH or specific gravity, and measured for protein in triplicate using iChem 10SG, iChem Velocity, and Multistix 8SG dipsticks. The pH experiment involved progressive alkalinization of urine aliquots with either 1M NaOH, Na2CO3, or NaHCO3; pH was recorded by electrode. The specific gravity experiment involved mixing aliquots with NaCl and spiking with human albumin. Urine electrolytes and total CO2 were measured (Roche cobas 8000). Fresh patient urines (N = 35) were analyzed for physiological urine pH and total CO2.
Urine protein results were not affected by NaOH alkalinization up to pH 10.9. False positive protein occurred at pH 9.9 and >97 mmol/L total CO2 (Na2CO3 alkalization; P < .05). Moreover, false positive protein occurred at pH 7.6 when total CO2 exceeded 137 mmol/L (NaHCO3 alkalization; P < .05). Fresh patient urines did not exceed pH 8.5 or 86 mmol/L total CO2. NaCl elevated specific gravity and caused false negative protein detection when urine ionic strength was >1100 mmol/L (P < .05).
Tetrabromphenol blue dipsticks provide robust detection of proteinuria when human urine is within physiological pH, total CO2 and ionic strength.
•Highly alkaline urine is unlikely to elicit false positive protein results with commercial urinalysis dipsticks•Total CO2 and pH could cause false positive protein detection at extreme levels which were not physiologically relevant•Specific gravity did not cause false negative protein detection but ionic strength was robustly associated with this effect
Very low high-sensitivity cardiac troponin T (hs-cTnT) thresholds on presentation can rule out acute myocardial infarction (AMI), but the ability to identify patients at low risk of 30-day major ...adverse cardiac events (MACE) is less clear. This study examines the sensitivity of low concentrations of hs-cTnT on presentation to rule out 30-day MACE.
This prospective cohort study enrolled patients with chest pain presenting to the emergency department with nonischemic electrocardiograms who underwent AMI rule-out with an hs-cTnT assay. The primary outcome was 30-day MACE; secondary outcomes were individual MACE components. Because guidelines recommend using a single hs-cTnT strategy only for patients with more than 3 hours since symptom onset, a subgroup analysis was performed for this population. Outcomes were adjudicated on the basis of review of medical records and telephone follow-up.
Of 1167 patients enrolled, 125 (10.7%) experienced 30-day MACE and 97 (8.3%) had AMI on the index visit. More than one-third of patients (35.6%) had presenting hs-cTnT concentrations below the limit of detection (5 ng/L), which was 94.4% (95% confidence interval CI, 88.8-97.7) sensitive for 30-day MACE and 99.0% (95% CI, 94.5-100) sensitive for index AMI. Of 292 patients (25.0%) with hs-cTnT < 5 ng/L and at least 3 hours since symptom onset, only 3 experienced 30-day MACE (sensitivity 97.6%; 95% CI, 93.2-100) and none had AMI within 30 days (sensitivity 100%; 95% CI, 96.3-100).
Among patients with nonischemic electrocardiograms and > 3 hours since symptom onset, low hs-cTnT thresholds on presentation confer a very low risk of 30-day MACE. In the absence of a high-risk clinical presentation, further risk stratification is likely to be low yield.
Un seuil de troponine T cardiaque hypersensible (TnTc-hs) très bas au moment de la consultation permet d’écarter le diagnostic d’infarctus aigu du myocarde (IAM), mais l’utilité de ce paramètre pour reconnaître les patients exposés à un faible risque d’événement cardiaque indésirable majeur (ECIM) à 30 jours est moins bien établie. Les auteurs examinent la sensibilité de la présence d’une faible concentration de TnTc-hs à la consultation comme critère pour écarter la possibilité d’un ECIM à 30 jours.
Ont été admis dans cette étude de cohorte prospective les patients qui se sont présentés à l’urgence en raison d’une douleur à la poitrine, dont l’électrocardiogramme n’a pas révélé d’ischémie et chez qui le diagnostic d’IAM a été écarté au moyen d’un dosage de la TnTc-hs. Le critère d’évaluation principal était la survenue d’un ECIM à 30 jours; les critères d’évaluation secondaires étaient les composantes individuelles de l’ECIM. Comme les lignes directrices recommandent le recours à un simple dosage de la TnTc-hs seulement pour les patients présentant des symptômes depuis plus de 3 heures, une analyse a été réalisée dans ce sous-groupe de la population à l’étude. Les critères d’évaluation ont été confirmés par un examen des dossiers médicaux et par un suivi téléphonique.
Des 1167 patients retenus, 125 (10,7 %) ont présenté un ECIM à 30 jours et 97 (8,3 %) avaient reçu un diagnostic d’IAM à la visite de référence. Au moment de la consultation, plus du tiers des patients (35,6 %) présentaient une concentration de TnTc-hs sous le seuil de détection (5 ng/l), ce qui représente une sensibilité de 94,4 % (intervalle de confiance IC à 95 % : de 88,8 à 97,7) dans le cas de l’ECIM à 30 jours et de 99,0 % (IC à 95 % : de 94,5 à 100) dans le cas de l’IAM de référence. Des 292 patients (25,0 %) présentant un taux de TnTc-hs < 5 ng/l et des symptômes apparus depuis au moins 3 heures, seulement 3 ont subi un ECIM à 30 jours (sensibilité de 97,6 %; IC à 95 % : de 93,2 à 100) et aucun n’a subi d’IAM dans les 30 jours (sensibilité de 100 %; IC à 95 % : de 96,3 à 100).
Chez les patients dont l’électrocardiogramme ne révèle pas d’ischémie et qui présentent des symptômes depuis au moins 3 heures, un seuil de TnTc-hs faible au moment de la consultation est associé à un très faible risque d’ECIM à 30 jours. En l’absence d’un tableau clinique associé à un risque élevé, il est peu probable qu’une stratification du risque plus poussée soit utile.
Here we validate a GC, Flame Ionization Detection (GC-FID), liquid injection method using hydrogen as a carrier gas combining analysis of toxic volatile alcohols (VA): methanol, ethanol, isopropanol, ...acetone, as well as glycols, ethylene glycol (EG) and propylene glycol (PG), in a single method.
200 μL of calibrator, QC, or patient specimen were deproteinized with 400 μL of acetonitrile containing internal standards (10 mmol/L N-propyl alcohol for VA and 2.5 mmol/L 1,2-butanediol for glycols). GC-FID analysis using hydrogen carrier gas and nitrogen makeup gas utilized an Agilent 7890 system equipped with Agilent 7683 liquid autosampler on a 30 m × 530 μm RTX-200 fused silica column. Method validation included repeatability, recovery, carryover, linearity, lower limit of quantification (LLOQ), accuracy, selectivity and measurement uncertainty.
The 8.3 min from injection to injection reduced time of analysis by 45% over a previously reported method using Helium carrier gas with no loss in resolution. Within-run and Between-run variability were ≤1.4% and ≤6.8% respectively. Recovery was 100% within a 95% confidence interval. Carryover was negligible for all but EG. LLOQ was <1 mmol/L for all analytes. The upper range of linearity was 120 mmol/L for methanol, ethanol and isopropanol, 100 mmol/L for acetone and 50 mmol/L for EG. Analytes demonstrated acceptable accuracy and measurement uncertainty using College of American Pathologists (CAP) criteria. Toluene can cause a false positive EG, while benzene, xylene and 1,3 butanediol can cause false negative EG.
Converting from Helium to Hydrogen carrier gas benefits patient care through a reduction in turnaround time and provides a cost savings to the laboratory.
The importance of offering on-site cardiac troponin (cTn) testing at pediatric hospitals may be underappreciated. We developed a rapid rule-in process for myocardial injury at a pediatric hospital ...experiencing delays in off-site high-sensitivity cardiac troponin T (hs-cTnT) testing.
Collect-to-verify turnaround times (TATs) for off-site testing were reviewed. Pre-analytic changes to improve TATs were devised, implemented and evaluated, after which a new analyzer was selected and evaluated for on-site cTn testing. Performance of the new analyzer's assay was compared to the off-site hs-cTnT assay, and post go-live TATs for on-site testing were assessed.
Median collect-to-verify TAT for short turnaround-time (STAT) priority off-site plasma hs-cTnT testing was 104 min, with 35% of orders having a TAT >120 min. Eliminating serum separator tubes and requiring a separate plasma separator tube did not significantly reduce TATs. A QuidelOrtho Triage® MeterPro whole blood cardiac troponin I (cTnI) assay was implemented to "triage" time-critical and STAT priority specimens collected for off-site hs-cTnT testing. Elevated cTnI (≥0.02 µg/L) had a sensitivity of 91% for clear elevations in hs-cTnT (≥53 ng/L) but a 0% sensitivity for modest elevations (5 to 13 ng/L, 14 to 52 ng/L). An interpretive comment was auto-appended to cTnI results indicating that clinicians should wait for the hs-cTnT result if cTnI was normal. Median collect-to-verify TAT for on-site cTnI testing was <50% the TAT for off-site hs-cTnT testing.
On-site point-of-care whole blood cTn testing can rapidly confirm significant or late-presenting myocardial injury. Combined with simultaneous off-site high-sensitivity cardiac troponin (hs-cTn) testing, this workflow is a viable interim solution for pediatric hospitals without on-site hs-cTn testing.
•Clinical tools and diagnostic signs and symptoms remain adequate at diagnosing NAS.•There is a significant gap in knowledge whether drug testing results are being used to confirm the diagnosis of ...NAS.•Each matrix (meconium, umbilical cord, and urine) has its own unique advantages and limitations.•There is a lack of standardization in the cut-off value and analyte profiles.•The goal of neonatal drug testing is to support the diagnosis of NAS, provide the appropriate follow-up and treatment for the mother-neonate dyad, not to identify maternal substance use disorder.
Illicit drug use during pregnancy is a concern worldwide, with many international studies describing attempted strategies to mitigate this problem. Drug misuse during pregnancy is associated with significant maternal as well as perinatal complications, which include a high incidence of stillbirths, fetal distress, neonatal abstinence syndrome (NAS) and increased neonatal mortality.
Unfortunately, the identification of a drug-exposed mother or neonate is challenging. Maternal disclosure of drug use is often inaccurate, principally due to psychosocial factors including behavioral denial or the fear of the consequences resulting from such admissions. Likewise, many infants who have been exposed to drugs in utero may appear normal at birth and initially show no overt manifestations of drug effects. Thus, the identification of the drug-exposed infant requires a high index of clinical suspicion. Conversely, analytical testing is an objective means of determining drug exposure when it may be necessary to document proof of the infant's exposure to illicit drugs.
The review will discuss the different matrices that are most commonly used for testing (e.g., maternal urine, neonatal urine, meconium, and umbilical cord), the strengths and limitations for each matrix, which drugs and metabolites are appropriate for testing, the various testing methods, and the advantages and disadvantages of each method.
Blood gas analyzers employing glucose-oxidase biosensors under-recover glucose when pO2 is low. The manufacturer of the GEM®Premier™ series of analyzers introduced an algorithm to detect specimens at ...risk of low pO2 interference. We investigated the reliability of this algorithm.
Whole blood specimens were tested by GEM®Premier™ 4000 (GEM 4000) and 5000 (GEM 5000). Specimens with an incalculable (“incalc”) error code for glucose result or that had a glucose ≥ 20 mmol/L were retested on a second analyzer of the same type within 5 min over the course of 30 months in 5 hospitals in Calgary, Alberta. Discordant retests were defined as either: 1) paired numeric results with a difference >10 %, or 2) an “incalc” code that yielded a numeric result upon retesting. Glucose recovery in relation to pO2 level was assessed by comparing specimens experimentally depleted of pO2 between GEM 5000 and a laboratory analyzer (Siemens Vista®).
Of 1,776 glucose tests repeated on the GEM 5000 or 1,544 on GEM 4000, 10% were discordant. GEM 5000 produced twice as many discordant numeric retests versus the GEM 4000 5.9% (98/1,651) vs 2.7% (38/1,391). The majority of “incalc” error codes repeated with a numeric glucose result on both GEM analyzers (79.7% (122/153) vs 75.2% (94/125). Among specimens experimentally depleted of pO2, the GEM 5000 under-recovered glucose by up to 30% compared to the Siemens Vista and were not flagged by an “incalc” code.
The algorithm in the GEM®PremierTM series of analyzers that flags specimens at risk for glucose under-recovery due to low pO2 does not reliably detect specimens at risk for glucose under-recovery.
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