The interobserver reliability of classification systems for radial head fractures: the Hotchkiss modification of the Mason classification and the AO classification systems

Background

Radial head fractures are common injuries, and there is little information on the reliability of classification systems for such injuries. The purpose of our study was to report the interobserver reliability of 2 commonly used classification systems: the Hotchkiss modification of the Mason classification and the AO classification systems.

Methods

We compiled the radiographs from a cohort series of 43 patients with radial head fractures, and 5 observers classified the radiographs according to both classification systems. Additionally, we collapsed the systems, with types II and III combined for the Hotchkiss classification and the final digit dropped for the AO classification. We calculated percent agreement, the κ statistic and the associated 95% confidence intervals (CIs).

Results

The mean percent agreement was 72.3% (95% CI 65.8%–78.9%) for the Hotchkiss classification and 37.7% (95% CI 30.5%–44.9%) for the AO classification. The κ statistic was 0.585 (0.541–0.661) for the Hotchkiss classification and 0.261 (0.240–0.350) for the AO classification. The mean percent agreement was 89.3% (86.6%–92.0%) for the consolidated Hotchkiss classification and 67.4% (54.6%–80.3%) for the consolidated AO classification. The κ statistic was 0.760 (0.691–0.805) for the consolidated Hotchkiss classification and 0.455 (0.372–0.521) for the consolidated AO classification.

Conclusion

The interobserver reliability for the Hotchkiss modification of the Mason classification was moderate, and that for the AO classification was fair according to the criteria of Landis and Koch. Collapsing the Hotchkiss classification improved the reliability to substantial, and collapsing the AO system improved reliability to the lower end of moderate.     

Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice

Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize glycolipid antigens in the context of the MHC class I-like antigen-presenting molecule CD1d. In vivo activation of mouse iNKT cells with the glycolipid alpha-galactosylceramide (alpha-GalCer) results in the acquisition of a hyporesponsive (anergic) phenotype by these cells. Because iNKT cells can become activated in the context of infectious agents, here we evaluated whether iNKT cell activation by microorganisms can influence subsequent responses of these cells to glycolipid antigen stimulation. We found that mouse iNKT cells activated in vivo by multiple bacterial microorganisms, or by bacterial LPS or flagellin, became unresponsive to subsequent activation with alpha-GalCer. This hyporesponsive phenotype of iNKT cells required IL-12 expression and was associated with changes in the surface phenotype of these cells, reduced severity of concanavalin A-induced hepatitis, and alterations in the therapeutic activities of alpha-GalCer. These findings may have important implications for the development of iNKT cell-based therapies.     

Measurement of serum acetaminophen-protein adducts in patients with acute liver failure

BACKGROUND & AIMS: Acetaminophen toxicity is the most common cause of acute liver failure (ALF) in the United States and Great Britain, but may be underrecognized in certain settings. Acetaminophen-protein adducts are specific biomarkers of drug-related toxicity in animal models and can be measured in tissue or blood samples. Measurement of serum adducts might improve diagnostic accuracy in acute liver failure (ALF) patients. METHODS: We measured serum acetaminophen-protein adducts using high-pressure liquid chromatography with electrochemical detection in coded sera of 66 patients with ALF collected prospectively at 24 US tertiary referral centers. Samples were included from 20 patients with well-characterized acetaminophen-related acute liver failure, 10 patients with ALF owing to other well-defined causes, 36 patients with ALF of indeterminate etiology, and 15 additional patients without ALF but with known acetaminophen overdose and minimal or no biochemical liver injury. RESULTS: Acetaminophen-protein adducts were detected in serum in 100% of known acetaminophen ALF patients and in none of the ALF patients with other defined causes, yielding a sensitivity and specificity of 100%. In daily serial samples, serum adducts decreased in parallel with aminotransferase levels. Seven of 36 (19%) indeterminate cases demonstrated adducts in serum suggesting that acetaminophen toxicity caused or contributed to ALF in these patients. Low adduct levels were present in 2 of 15 patients with acetaminophen overdose without significant liver injury. CONCLUSIONS: Measurement of serum acetaminophen-protein adducts reliably identified acetaminophen toxicity, and may be a useful diagnostic test for cases lacking historical data or other clinical information.     

ACR Appropriateness Criteria Right Lower Quadrant Pain—Suspected Appendicitis

The diagnostic imaging of patients presenting with right lower quadrant pain and suspected appendicitis may be organized according to age and gender and to the presence or absence of "classic" signs and symptoms of acute appendicitis. Among adult patients presenting with clinical signs of acute appendicitis, the sensitivity and specificity of CT are greater than those of ultrasound, with improved performance when CT is performed with intravenous contrast. The use of rectal contrast has been associated with decreased time in the emergency department. Computed tomography has also been shown to reduce cost and negative appendectomy rates. Both CT and ultrasound are also effective in the identification of causes of right lower quadrant pain unrelated to appendicitis. Among pediatric patients, the sensitivity and specificity of graded-compression ultrasound can approach those of CT, without the use of ionizing radiation. Performing MRI after inconclusive ultrasound in pregnant patients has been associated with sensitivity and specificity of 80% to 86% and 97% to 99%, respectively. The ACR Appropriateness Criteria(?) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.     

Comparative analysis of drug response and gene profiling of HER2-targeted tyrosine kinase inhibitors

Background Human epidermal growth factor 2 (HER2/ERBB2) is frequently amplified/mutated in cancer. The tyrosine kinase inhibitors (TKIs) lapatinib, neratinib, and tucatinib are FDA-approved for the treatment of HER2-positive breast cancer. Direct comparisons of the preclinical efficacy of the TKIs have been limited to small-scale studies. Novel biomarkers are required to define beneficial patient populations.Methods In this study, the anti-proliferative effects of the three TKIs were directly compared using a 115 cancer cell line panel. Novel TKI response/resistance markers were identified through cross-analysis of drug response profiles with mutation, gene copy number and expression data.Results All three TKIs were effective against HER2-amplified breast cancer models; neratinib showing the most potent activity, followed by tucatinib then lapatinib. Neratinib displayed the greatest activity in HER2-mutant and EGFR-mutant cells. High expression of HER2, VTCN1, CDK12, and RAC1 correlated with response to all three TKIs. DNA damage repair genes were associated with TKI resistance. BRCA2 mutations were correlated with neratinib and tucatinib response, and high expression of ATM, BRCA2, and BRCA1 were associated with neratinib resistance.Conclusions Neratinib was the most effective HER2-targeted TKI against HER2-amplified, -mutant, and EGFR-mutant cell lines. This analysis revealed novel resistance mechanisms that may be exploited using combinatorial strategies.Subject terms: Tumour biomarkers, Targeted therapies     

Differential effects of toremifene on doxorubicin, vinblastine and Tc-99m-sestamibi in P-glycoprotein-expressing breast and head and neck cancer cell lines

The effect of toremifene on P-glycoprotein-mediated multidrug resistance (MDR) in breast and head and neck cancer cell lines was measured in vitro and in vivo. Pgp expression was low and high, respectively, in drug-sensitive (MCF7-S, KB) and drug-resistant (MCF7-R, MCF7-R1, KBV1) cell lines. Toremifene (7.5 microM) significantly enhanced cytoplasmic and nuclear accumulation of doxorubicin in drug-resistant cells. Toremifene (10 microM) increased the in vitro cytotoxicity of doxorubicin in drug-resistant breast cancer cells (13-fold and 21-fold for MCF7-R and MCF7-R1, respectively) without affecting the sensitivity of MCF7-S cells. Similarly, toremifene (10 microM) caused a 12-fold increase in the sensitivity of KBV1 cells to vinblastine. In contrast, toremifene (5 microM) reduced the net uptake of the radiolabelled Pgp substrate, Tc-99m-sestamibi, in the Pgp-overexpressing cell lines by factors of 0.32 and 0.42 for MCF7-R1 and KBV1 cells, respectively (p < 0.01), and, to a lesser extent, by corresponding factors of 0.89 and 0.86 in the drug-sensitive cell lines (p < 0.05 and p > 0.05, respectively). In nude mice bearing both KB and KBV1 xenograft tumours, significantly higher tumour levels of Tc-99m-sestamibi were recorded in KB tumours compared with KBV1 tumours. After 3 days of treatment with intraperitoneal toremifene (25 mg/kg), tumour levels of Tc-99m-sestamibi were reduced in KB and KBV1 tumours but only statistically significantly for KB tumours. Toremifene is a potent MDR modulating agent with respect to chemotherapeutic agents but has the opposite effect with respect to Tc-99m-sestamibi. This finding is of importance in view of the widespread use of Tc-99m-sestamibi as an imaging surrogate for a chemotherapeutic agent.     

The placenta revisited: radiologic-pathologic correlation

The placenta is the central support organ for the developing fetus. Recognition of placental variants and insignificant findings is important so as not to suggest an abnormality when one is not present. However, the degree of abnormality, as well as the clinical implications of the findings, must be understood to help guide management of the pregnancy. This article reviews the normal sonographic appearance of the placenta and some anatomic variants, in addition to illustrating various common pathological conditions of the placenta and correlating with gross pathologic and histologic specimens.