A phase I trial of docetaxel based induction and concomitant chemotherapy in patients with locally advanced head and neck cancer

The purpose of this study was to determine the maximum tolerated dose (MTD) of docetaxel based induction and concomitant chemoradiotherapy (CRT) after using the FHX platform (5 = 5-FU, H = hydroxyurea, X = Radiation). Patients with Stage III/IV locally advanced HNSCC were enrolled. Induction chemotherapy (carboplatin/docetaxel) was followed by 5 cycles of concomitant docetaxel based CRT. No DLTs were observed in dose levels 1/2 for induction and CRT. Dose level 2 was expanded. The overall survival CR rate after CRT was 79 percent. Median overall (OS) has not been reached and 2-year OS is 80.7 percent. The recommended Phase II dose of docetaxel with FHX CRT is 25 mg/m² and 35 mg/m² in combination with carboplatin induction (AUC = 6).     

p53 mutations in deep tissues are more strongly associated with recurrence than mutation-positive mucosal margins.

PURPOSE: Application of ultrasensitive diagnostics has shown that small numbers of p53 mutation-positive cells may signify the presence of residual tumor in histologically normal tissues after resection of squamous cell carcinomas arising in the head and neck area. To date, most studies in this area have focused on analysis of tissues at the mucosal aspect of the resection and highlighted the importance of molecular changes in the field with respect to the risk of recurrence. EXPERIMENTAL DESIGN: In the present investigation, we analyzed normal tissues from mucosal and deep surgical margins, referred to as "molecular margins," for the presence of the signature p53 mutation identified for each tumor. RESULTS: The p53 mutation status of these carcinomas did not correlate with clinical or histopathologic variables, but these mutations provided an excellent target for ultrasensitive analysis of margin status. We found that 11 of 16 (68%) of cases with histologically tumor-free (including 9 without dysplasia), but with p53 mutation-positive molecular margins, developed recurrence. The probability of developing local recurrence was significantly higher for the group with p53 mutation-positive margins when compared with the group with clear margins (P = 0.048) and more strongly associated with p53 mutation-positive deep molecular margins than mutation-positive mucosal molecular margins or positivity at both sites (P = 0.009). CONCLUSIONS: This shows that although persistent mucosal fields may contribute to recurrence, clonal p53 mutations in deep tissues are an important cause of treatment failure, and molecular margins from both sites should be analyzed in future prospective series.     

Case 33. Diagnostic difficulty in a patient with acute leukemia

A provisional diagnosis of acute myeloid leukemia, FAB type M2, was made in a 24-year-old woman. Immunophenotyping led to reassessment of the diagnosis.     

Reference values for hair cotinine as a biomarker of active and passive smoking in women of reproductive age, pregnant women, children, and neonates: systematic review and meta-analysis

Exposure to environmental tobacco smoke (ETS) is most often estimated using questionnaires, but they are unreliable. Biomarkers can provide valid information on ETS exposure, the preferred biomarker being cotinine. However, no reference range of hair cotinine exists to distinguish among active, passive, and unexposed nonsmokers. This study identifies cutoffs to validate cotinine as a marker for exposure to ETS. Data were obtained from six databases (four US, one Canada, one France). Active smoking and exposure to ETS were measured in the hair of women of reproductive age, pregnant women, their children, and neonates. Subjects were classified into active smokers, passively exposed to ETS, and unexposed nonsmokers. A total of 1746 cases were available for analysis. For active smokers, mean hair cotinine concentrations (95% confidence interval) were 2.3 to 3.1 ng/mg for nonpregnant women and 1.5 to 1.9 ng/mg for pregnant women. In the group of passive smokers, mean hair cotinine concentrations were 0.5 to 0.7 ng/mg for nonpregnant women, 0.04 to 0.09 ng/mg for pregnant women, 0.9 to 1.1 for children, and 1.2 to 1.7 for neonates. Among unexposed nonsmokers, mean hair cotinine was 0.2 to 0.4 ng/mg in nonpregnant women, 0.06 to 0.09 ng/mg in pregnant women, and 0.3 to 0.4 ng/mg in children. Cutoff values for hair cotinine were established to distinguish active smokers from passive or unexposed (0.8 ng/mg for nonpregnant women and 0.2 ng/mg for pregnant women). A cutoff value of 0.2 ng/mg was accurate in discriminating between exposed children and unexposed. These new values should facilitate clinical diagnosis of active and passive exposure to tobacco smoke. Such diagnosis is critical in pregnancy and in a large number of tobacco-induced medical conditions.     

Direction of gaze effects on early face processing: eyes-only versus full faces

The N170 event-related potential (ERP) reflects an early stage of face processing. We wished to determine if it would also index the intuitively important information provided by direction of gaze. Two studies were run. In one, stimuli included full faces with the eyes looking forward, to the left or closed; in the other study the stimuli included eyes-only, looking forward, left or closed. Gaze direction had no effects on amplitude, but longer latencies were found for faces with eyes closed. With eyes-only stimuli, more marked effects on latencies and borderline effects on amplitudes were seen. We suggest that there can only be limited evidence of gaze-specific sensitivity in ERP studies in humans, without eye movement.     

Clinical data sharing improves quality measurement and patient safety

ObjectiveAccurate and robust quality measurement is critical to the future of value-based care. Having incomplete information when calculating quality measures can cause inaccuracies in reported patient outcomes. This research examines how quality calculations vary when using data from an individual electronic health record (EHR) and longitudinal data from a health information exchange (HIE) operating as a multisource registry for quality measurement. Materials and MethodsData were sampled from 53 healthcare organizations in 2018. Organizations represented both ambulatory care practices and health systems participating in the state of Kansas HIE. Fourteen ambulatory quality measures for 5300 patients were calculated using the data from an individual EHR source and contrasted to calculations when HIE data were added to locally recorded data.ResultsA total of 79% of patients received care at more than 1 facility during the 2018 calendar year. A total of 12 994 applicable quality measure calculations were compared using data from the originating organization vs longitudinal data from the HIE. A total of 15% of all quality measure calculations changed (P < .001) when including HIE data sources, affecting 19% of patients. Changes in quality measure calculations were observed across measures and organizations.DiscussionThese results demonstrate that quality measures calculated using single-site EHR data may be limited by incomplete information. Effective data sharing significantly changes quality calculations, which affect healthcare payments, patient safety, and care quality.ConclusionsFederal, state, and commercial programs that use quality measurement as part of reimbursement could promote more accurate and representative quality measurement through methods that increase clinical data sharing.     

Replication of genetic associations in the inflammation, complement, and coagulation pathways with intraventricular hemorrhage in LBW preterm neonates

Intraventricular hemorrhage (IVH) is a significant morbidity seen in very LBW infants. Genes related to the inflammation, infection, complement, or coagulation pathways have been implicated as risk factors for IVH. We examined 10 candidate genes for associations with IVH in 271 preterm infants (64 with IVH grades I-IV and 207 without IVH) weighing <1500 g. The heterozygous genotype OR = 8.1, CI = 2.5-26.0, p = 4 × 10(-4)) and the A allele (OR = 7.3, CI = 2.4-22.5, p = 1 × 10(-4)) of the coagulation factor V (FV) Leiden mutation (rs6025) were associated with an increased risk of developing IVH grade I or II but not grade III or IV after correction for multiple testing with Bonferroni. Lack of association in the severe grades of IVH may be a result of lack of power to detect an effect given the small sample size (n = 8). However, this result is consistent with previous research that demonstrates that the heterozygous genotype of the FV mutation is associated with increased risk for the development of IVH but a decreased risk for the progression or extension to more severe grades of IVH.     

Behavior outbursts, orofacial dyskinesias, and CSF pleocytosis in a healthy child

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis represents a new category of immune-mediated neurologic disorders. Viral encephalitis is often the presumptive diagnosis because of the acute neurologic changes, cerebrospinal fluid lymphocytic pleocytosis, and occasional hyperthermia. We report here the case of a previously healthy 7-year-old boy with new-onset aggressive behavior, seizure activity, and orofacial dyskinesias with cerebrospinal fluid and serum that tested positive for anti-NMDA receptors.