Diagnostic yield of high-density versus low-density EEG: The effect of spatial sampling,timing and duration of recording

ObjectiveTo investigate the effect of spatial sampling and of recording duration on the diagnostic yield of EEG for identification of interictal epileptiform discharges (IEDs). Previous studies demonstrated that high-density (HD) recordings increased accuracy of localization compared to low-density (LD) recordings.MethodsWe have prospectively evaluated the effect of spatial sampling and of recording duration in patients who had short-term (ST) recordings with a HD array of 256 electrodes following long-term (LT) recordings with a LD array consisting of the standard IFCN array of 25 electrodes. IED clusters were identified in four datasets: LT-LD, ST-LD (spatially down-sampled to the standard IFCN array), ST-HD and a shortened (90 minutes) epoch of LT-LD.ResultsSixty consecutive patients were recruited. We identified 89 IED clusters totally. Two clusters were found by increasing spatial sampling from 25 to 256 electrodes. This modest increase was not statistically significant. Eight clusters were missed by reducing the recording duration to 90 minutes, as compared with the LT recordings (p = 0.003).ConclusionsRecording duration is more important for the diagnostic yield of EEGs than increasing spatial sampling beyond the standard IFCN electrode array.SignificanceThe standard IFCN electrode array provides sufficient spatial sampling for identification of the IEDs.     

Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer

Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1(V561M)), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.     

A mutant human IgG molecule with only one C1q binding site can activate complement and induce lysis of target cells

There are potentially two binding sites for C1q on IgG, one on each C(H)2 domain of the gamma heavy chains, close to the lower hinge region. It is not clear whether the presence and involvement of both the C1q binding sites is necessary to induce the activation signal of human IgG. In order to clarify this issue, we made a hybrid mutant IgG1/IgG3 molecule where the IgG1 half of the molecule was made unable to activate complement through the introduction of a P329A mutation. The IgG3 half of the molecule was mutated to harbor a hinge region identical to that of IgG1, and for detection a peptide tag derived from p21ras was introduced into the FG loop of the C(H)1 domain. The hybrid IgG1P329A/IgG3h1-ras molecules were isolated by Protein A affinity chromatography and shown to activate complement and induce complement-mediated lysis at the same levels as wild-type IgG1 and IgG3h1-ras molecules. Thus, one C1q binding site per IgG is sufficient to induce activation. Wild-type human IgG molecules might also normally expose only one C1q binding site as already shown for interaction with FcgammaR, were IgG expose one binding site per molecule.     

Nose- and sinus-related quality of life and GERD

Though some data indicate an association between gastroesophageal reflux disease (GERD) and upper airway inflammatory disease, a connection between GERD and chronic rhinosinusitis (CRS) is a matter of controversy in today’s medicine. The aim of this study was to examine whether patients with GERD have a different nose- and sinus-related quality of life compared to a control group. A total of 77 patients with GERD diagnosed by gastroscopy were evaluated according to their nose- and sinus-related quality of life. It was scored using the Sino-Nasal Outcome Test-20 (SNOT-20). Total SNOT-20 score was compared with a control group consisting of 480 teachers. The average total SNOT-20 score in patients with GERD was 22.1, and in the control group 9.4 (p < 0.005). In the patient group, the median was 17.0 and standard deviation 18.4 corresponding to 5.0 and 11.5 in the controls. The 95% confidence interval in the patient group was (18.0, 26.3), and (8.3, 10.4) in the control group. Patients with GERD have a reduced nose- and sinus-related quality of life compared to a control group based on the fact that they have a significantly higher total SNOT-20 score than the controls. Accordingly, this study indicates that there is a causal relationship between GERD and CRS.