Diagnostic misclassification reduces the ability to detect linkage in inflammatory bowel disease genetic studies.

BACKGROUND: Linkage data have now identified several inflammatory bowel disease (IBD) susceptibility loci but these data have not been consistently replicated in independent studies. One potential explanation for this is the possibility that patients enrolled in such studies may have been erroneously classified with respect to their diagnosis. AIMS: To determine the rate and type of misclassification in a large population of individuals referred for participation in an IBD genetics study and to examine the effect of diagnostic misclassification on the power to detect linkage. METHODS: The medical records of 1096 patients entered into an IBD genetics programme were reviewed using standardised diagnostic criteria. The original patient reported diagnoses were changed, if necessary, based on review, and the reasons for the change in diagnosis were recorded. To evaluate the effect of misclassification on linkage results, simulations were created with Gensim and analysed using Genehunter to evaluate a model for IBD inheritance. RESULTS: Sixty eight of 1096 (6.2%) individuals had a change in diagnosis from that originally reported. The majority of changes were patients with either Crohn's disease or ulcerative colitis who were determined not to have IBD at all. The principal reasons for changes to the original diagnosis were discordance between the patients' subjective reports of diagnosis and actual clinical history, endoscopic, or pathological results; a change in disease pattern over time; and insufficient information available to confirm the original diagnosis. A 10% misclassification rate resulted in 28.4% and 40.2% loss of power to detect a true linkage when using a statistical model for a presumed IBD locus with lambda(s) values of 1.8 and 1.3, respectively. CONCLUSIONS: Diagnostic misclassification occurs in patients enrolled in IBD genetic studies and frequently involves assigning the diagnosis of IBD to non-affected individuals. Even low rates of diagnostic misclassification can lead to significant loss of power to detect a true linkage, particularly for loci with modest effects as are likely to be found in IBD.     

A safe surgical technique for the infradiaphragmatic removal of caval tumor thrombus complicating renal cell carcinoma

The management of patients with renal cell cancer extending to the vena cava is controversial and challenging. Careful planning of the operative procedure, adequate exposure, complete mobilization of the retrohepatic vena cava and control of the hepatic venous effluence will allow patients with retrohepatic vena caval occlusions to be managed safely and successfully. The major advantage of this technique is the minimizing of both peroperative bleeding and circulatory and biochemical disturbances of the liver due to the interruption of the blood flow.     

BRAF Mutant Lung Cancer: Programmed Death Ligand 1 Expression,Tumor Mutational Burden,Microsatellite Instability Status,and Response to Immune Check-Point Inhibitors

Introduction

The efficacy of immune checkpoint inhibitors (ICPi) in BRAF mutant NSCLC is unknown.

Immunotherapy for Head and Neck Squamous Cell Carcinoma

Purpose of Review

Discussion of current strategies targeting the immune system related to solid tumors with emphasis on head and neck squamous cell carcinoma (HNSCC).This review will outline the current challenges with immunotherapy and future goals for treatment using these agents.

Recent Findings

Agents targeting immune checkpoint receptors (IR) such as program death 1 (PD1) have been used in the clinical realm for melanoma and non-small cell lung cancer (NSCLC), and the use of these agents for these malignancies has provided crucial information about how and why patients respond or not to inhibitory checkpoint receptor blockade therapy (ICR). The anti PD1 agent, nivolumab, was recently approved by the FDA as a standard of care regimen for patients with platinum refractory recurrent/metastatic (R/M) HNSCC. Molecular pathways leading to resistance are starting to be identified, and work is underway to understand the most optimal treatment regimen with incorporation of immunotherapy.

Summary

ICR has renewed interest in the immunology of cancer, but resistance is not uncommon, and thus understanding of these mechanisms will allow the clinician to appropriately select patients that will benefit from this therapy.

     

Influence of sex and disease on illness-related concerns in inflammatory bowel disease.

Identifying the normal concerns of people with ulcerative colitis and Crohn's disease (CD) facilitates a comprehensive approach to their medical care. Clinically, it can be easily appreciated that the concerns of men and women with inflammatory bowel disease (IBD) may differ and that this may have a substantial impact on both coping and treatment decisions. However, sex differences have received little empirical study. METHODS: Significant differences between the sexes on the 25 items of the Rating Form of IBD Patient Concerns (RFIPC) were determined in 343 subjects by univariate ANOVA with disease type and sex as factors, correcting for multiple comparisons and covarying for IBD symptom severity. RESULTS: Compared with men, women reported higher levels of IBD symptom severity and higher overall RFIPC scores. Women were more concerned than men about feelings related to their bodies, attractiveness, feeling alone and having children. There was an interaction between disease and sex regarding concern about sexual performance and intimacy. In both cases, men with CD reported less concern than each other comparison group. The illness concerns that differ between sexes are not the most intense concerns in either sex. DISCUSSION: These results confirm that sex has a significant influence on a number of illness concerns, particularly concerns related to self-image and relationships. The interaction of disease type and sex with respect to concern over sexual performance and intimacy is open to several potential explanations and requires further research. Sex differences should be considered in the treatment of IBD. Specific inquiry into sex-specific concerns may be useful for the clinician. Further research is required to replicate these retrospective findings.     

Open-window mapping of accessory pathways utilizing high-density mapping

Journal of Interventional Cardiac Electrophysiology - Accessory pathway (AP) mapping is currently based on point-by-point mapping and identifying if a local electrogram’s origin is atrial,...     

Does Oral Enzyme Replacement Therapy Reverse Intestinal Lactose Malabsorption?

The effects of oral enzyme replacement therapy on breath hydrogen excretion and symptoms after milk ingestion were studied in lactase-deficient patients. Sixteen symptomatic patients underwent interval hydrogen breath tests using whole milk as substrate. Each study was repeated with the addition of 250 mg of β-D-galactosidase derived from Aspergillus oryzae (Lactrase) given orally with the milk. Subsequently seven of those 11 patients who did not normalize their hydrogen excretion with 250 mg of Lactrase were available to be restudied with a 500-mg dose. Mean cumulative and peak hydrogen excretions were calculated for the baseline (milk alone), 250 mg, and 500 mg Lactrase groups. Significant (p ≤ 0.05) decreases in cumulative and peak hydrogen excretion were noted between the 500 mg Lactrase versus the baseline group, but not between the 250 mg versus baseline group. Five of the 16 (31%) symptomatic lactase-deficient patients normalized their hydrogen excretion after 250 mg of Lactrase; four of seven (57%) who bad not normalized on 250 mg, normalized their hydrogen excretion with 500 mg of Lactrase. A different pattern was observed in the incidence of symptoms. Five of the nine patients (56%) whose hydrogen excretion normalized with the addition of Lactrase at either dosage became asymptomatic after milk ingestion; in addition, three patients who did not normalize their hydrogen also became asymptomatic. We conclude that oral Lactrase in sufficient dosage temporarily reverses lactose malabsorption in some patients.