Epileptic patients refractory to drug therapy

We compared two groups of patients with idiopathic epilepsy, 41 patients whose seizure frequency was not controlled by adequate therapy and 39 patients in good seizure control, in respect of hematology, kidney and liver function tests, serum IgG, IgA and IgM concentrations and drug concentrations. The only difference that emerged were in the serum immunoglobulins, which were raised in the drug refractory group, significantly (p less than 0.01) so in the case of IgG. Failure of seizure control did not depend on inadequacy of drug dose or of blood concentration. Although the serum Ig changes do not warrant the assumption of an immunological origin for drug resistance, they do suggest a useful research line.     

Identification of dermatophyte species by 28S ribosomal DNA sequencing with a commercial kit

We have shown that dermatophyte species can be easily identified on the basis of a DNA sequence encoding a part of the large-subunit (LSU) rRNA (28S rRNA) by using the MicroSeq D2 LSU rRNA Fungal Sequencing Kit. Two taxa causing distinct dermatophytoses were clearly distinguished among isolates of the Trichophyton mentagrophytes species complex.     

Immunophenotypic analysis of the transformation zone of human cervix

The immunocompetent cell population of the cervical transformation zone of 18 uteri removed for noncervical disease, has been investigated with monoclonal antibodies. The panel included Leu 2a, 3a, 4, 14, and IL II receptor for lymphocytes and T cell subsets, Leu 7 for NK cells, Leu M5, Leu 10, HLA-DR, DRC 1 for dendritic cells, and Leu 6 for Langerhans' cells (LC). In ectocervical epithelium HLA-DR, Leu 6 and Leu 10 antibodies identified subpopulations of dendritic cells which differed in number and in topographic distribution. Furthermore, a strong HLA-DR epithelial positivity was constantly observed in endocervical columnar cells as well as in keratinocytes of squamous metaplasia. Leu 2a+ cells (T suppressor/cytotoxic) prevailed in the stromal and epithelial compartments of ecto/endocervix; in 6 cases, however, Leu 3a+ cells (T helper/inducer) represented the main T cell subset in the ectocervical stroma. B lymphocytes were occasionally noticed in the subepithelial stroma while NK and DRC-1 cells were never observed. Finally, only few lymphocytes displayed a positivity for IL II receptor. This study suggests that several phenotypes of intraepithelial dendritic cells are present in the transformation zone and that endocervical columnar cells and keratinocytes of squamous metaplasia express HLA-DR products; the latter finding may be related to the presence of intraepithelial and stromal T lymphocytes.     

Comparison of HE4, CA125 and ROMA algorithm in women with a pelvic mass: Correlation with pathological outcome

ObjectiveThe quality of first surgery is one of the most important prognostic factors in ovarian cancer patients. Pre-surgical distinction of benign and malignant pelvic mass plays a critical role in ovarian cancer management and survival. The aim of this study was to evaluate the clinical performance of ROMA algorithm and of CA125 and HE4 in the triage of patients with a pelvic mass undergoing surgery, in order to discriminate benign from malignant disease.MethodsThree hundred and forty-nine pre- and post-menopausal women, aged 18 years or older undergoing surgery because of a pelvic mass were enrolled: serum concentrations of CA125 and HE4 were determined and ROMA was calculated for each sample.ResultsMedian serum CA125 and HE4 levels were higher in patients with EOC compared to subjects with benign disease (p < 0.0001). The resultant accuracy (using Receiver Operating Characteristics, ROC Area) values for HE4, CA125 and ROMA showed a good performance ranging from 89.8% for CA125 in pre-menopausal patients to 93.3% for ROMA in post-menopausal patients: AUC for ROMA resulted significantly higher in comparison to CA125 alone (93.3% vs 90.3%, p = 0.0018) in post menopausal patients. A sub-analysis considering the 40 patients with endometrioid disease showed the highest accuracy of HE4 in these patients.ConclusionsData presented confirm the accuracy of HE4 and of the ROMA algorithm in the distinction of ovarian carcinoma from benign disease, with a trend towards better performance for ROMA than for CA125 alone, statistically significant in postmenopausal patients.     

Metrics and tools for consistent cohort discovery and financial analyses post-transition to ICD-10-CM

In the United States, International Classification of Disease Clinical Modification (ICD-9-CM, the ninth revision) diagnosis codes are commonly used to identify patient cohorts and to conduct financial analyses related to disease. In October 2015, the healthcare system of the United States will transition to ICD-10-CM (the tenth revision) diagnosis codes. One challenge posed to clinical researchers and other analysts is conducting diagnosis-related queries across datasets containing both coding schemes. Further, healthcare administrators will manage growth, trends, and strategic planning with these dually-coded datasets. The majority of the ICD-9-CM to ICD-10-CM translations are complex and nonreciprocal, creating convoluted representations and meanings. Similarly, mapping back from ICD-10-CM to ICD-9-CM is equally complex, yet different from mapping forward, as relationships are likewise nonreciprocal. Indeed, 10 of the 21 top clinical categories are complex as 78% of their diagnosis codes are labeled as “convoluted” by our analyses. Analysis and research related to external causes of morbidity, injury, and poisoning will face the greatest challenges due to 41 745 (90%) convolutions and a decrease in the number of codes. We created a web portal tool and translation tables to list all ICD-9-CM diagnosis codes related to the specific input of ICD-10-CM diagnosis codes and their level of complexity: “identity” (reciprocal), “class-to-subclass,” “subclass-to-class,” “convoluted,” or “no mapping.” These tools provide guidance on ambiguous and complex translations to reveal where reports or analyses may be challenging to impossible.Web portal: http://www.lussierlab.org/transition-to-ICD9CM/Tables annotated with levels of translation complexity: http://www.lussierlab.org/publications/ICD10to9     

HPV genotype distribution according to severity of cervical neoplasia using the digene HPV genotyping LQ test

A new genotyping-based DNA assay (Digene LQ^®) was developed recently. The primary aim was to assess the distribution of HPV types using this new assay in atypical squamous cells of undeterminate significance (ASCUS). The secondary aim was to correlate the HPV types with the severity of the disease. The study population comprised 376 ASCUS women. The women were all Hybrid Capture II (HCII) positive and were admitted in three European referral gynecology clinics between 2007 and 2010. A colposcopy with histological examination was performed in all these patients. HPV 16 was typed in 40 % of patients, HPV 18 in 7 %, and HPV 31 in 17 %, and 18 % of patients had mixed genotypes. Patients aged over 30 more often had the HPV 16 genotype than patients aged under 30 (29 % vs. 11 %, chi-square test p < 0.001). The risk of cervical intra-epithelial neoplasia of grade 2 or more (CIN2 +) when HPV 18 positive is lower than the probability associated with HPV 16 or HPV 31: 28 % vs. 58 % and 52 %, respectively (chi-square test, p = 0.005 and p = 0.05, respectively). The Digene LQ^®, a new sequence-specific hybrid capture sample preparation, is fast and efficient and allows high-throughput genotyping of 18 HR HPV types by PCR compared to traditional non-sequence-specific sample preparation methods.     

The Role of Psychological Sense of School Membership and Postcode as Predictors of Profiles of Socio-emotional Health in Primary School Children in England

School Mental Health - A dual approach to mental health in schools has been widely defended, where the assessment of psychological distress and the examination of strengths/well-being are two...     

EGFR gene gain and PTEN protein expression are favorable prognostic factors in patients with KRAS wild-type metastatic colorectal cancer treated with cetuximab

Introduction

Cetuximab is a monoclonal epidermal growth factor receptor (EGFR)-targeting antibody, used in the treatment of colon cancer. KRAS mutation status is strongly predictive of cetuximab efficacy, but more predictive factors are needed for better patient selection. PTEN is a downstream inhibitor of the EGFR pathway and has been evaluated as a predictive factor of cetuximab efficacy in colorectal cancer.

Patients and methods

Formalin-fixed paraffin-embedded tumor tissue samples were collected from 226 patients with advanced or metastatic colorectal cancer that had been treated with cetuximab. Clinical information was collected retrospectively from the patients’ medical records. After central evaluation, 147 cases with adequate material were eligible for further evaluation. EGFR and PTEN status was evaluated with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Data were associated with cetuximab treatment outcome. Additional analysis was performed with previously published data on PIK3CA, BRAF and KRAS mutation status and EGFR ligand amphiregulin (AREG) and epiregulin intratumoral mRNA expression levels. PIK3CA mutation status and PTEN protein expression were also analyzed as a single complex parameter, to evaluate the predictive value of PI3K/PTEN axis dysfunction as one entity.

Results

Analysis showed a borderline association of overall response rate (ORR) and time to progression (TTP) with EGFR protein overexpression by IHC (p = 0.059 and p = 0.057, respectively) and a positive association of EGFR gain by FISH (found in only five cases) with longer TTP (p = 0.026). No association was found between ORR or TTP and PTEN IHC or FISH status. Comparative analysis with previously published data showed that PTEN protein expression is associated with longer TTP in patients with wild-type (WT) KRAS (p = 0.036) and especially in the ones with elevated AREG levels (p = 0.046), as well as in patients with both KRAS and BRAF WT (p = 0.019). Patients with both PIK3CA WT and PTEN protein expression had significantly longer TTP (p = 0.010) versus all others, in the absence of BRAF and KRAS mutations, a finding which persisted in the KRAS WT/AREG high subgroup (p = 0.046).

Conclusions

In this cetuximab-treated colorectal cancer population, EGFR gain was associated with better outcome and PTEN protein expression with longer TTP in KRAS WT, KRAS WT/AREG high and KRAS/BRAF WT subpopulations. Cetuximab efficacy is greater with intact and activated EGFR signaling, without activating mutations of KRAS/BRAF and in the presence of preserved PTEN inhibitory activity upon the PI3K/AKT pathway. These results reflect a solid biological rationale and warrant further evaluation of the predictive role of PTEN in prospective studies.     

Prognostic value of pathological patterns of lymph node positivity in squamous cell carcinoma of the vulva Stage III and IVA FIGO

Lymph node positivity in invasive squamous cell vulvar cancer implies a severe decrease in survival rates. Pathological lymph node positivity covers a wide range of metastatization patterns. In the present investigation the nodal positivity of 53 patients affected by Stage III and IVA invasive vulvar squamous cell carcinoma has been carefully evaluated and correlated with survival. Number, size of the metastasis inside the node, intracapsular or extracapsular site of the metastasis, and immune response of the positive nodes were considered. Cancer-related survival has been obtained for the whole study group (53 cases), for the patients with monolateral node positivity (36 cases), and for the patients showing only one positive node (19 cases). The diameter and the site of the metastasis were significantly correlated with survival in all three groups studied. Patients showing an intracapsular positivity or a size of metastasis less than 5 mm had a 5-year cancer-related survival of almost 90%, while patients showing a metastasis larger than 15 mm or an extracapsular site had a 20% survival. The results demonstrate that patients affected by invasive squamous cell vulvar cancer with positive nodes can be divided into two groups with a significantly different survival according to the histopathological pattern of lymph node invasion.