Validity of the Bern Score as a Surrogate Marker of Clinical Severity in Patients with Spontaneous Intracranial Hypotension.

BACKGROUND AND PURPOSE: The Bern score is a quantitative scale characterizing brain MR imaging changes in spontaneous intracranial hypotension. Higher scores are associated with more abnormalities on brain MR imaging, raising the question of whether the score can serve as a measure of disease severity. However, the relationship between clinical symptom severity and the Bern score has not been evaluated. Our purpose was to assess correlations between Bern scores and clinical headache severity in spontaneous intracranial hypotension. MATERIALS AND METHODS: This study was a single-center, retrospective cohort of patients satisfying the International Classification of Headache Disorders-3 criteria for spontaneous intracranial hypotension. Fifty-seven patients who completed a pretreatment headache severity questionnaire (Headache Impact Test-6) and had pretreatment brain MR imaging evidence of spontaneous intracranial hypotension were included. Pearson correlation coefficients (ρ) for the Headache Impact Test-6 and Bern scores were calculated. Receiver operating characteristic curves were used to assess the ability of Bern scores to discriminate among categories of headache severity. RESULTS: We found low correlations between clinical headache severity and Bern scores (ρ = 0.139; 95% CI, -0.127-0.385). Subgroup analyses examining the timing of brain MR imaging, symptom duration, and prior epidural blood patch showed negligible-to-weak correlations in all subgroups. Receiver operating characteristic analysis found that the Bern score poorly discriminated subjects with greater headache severity from those with lower severity. CONCLUSIONS: Pretreatment Bern scores show a low correlation with headache severity in patients with spontaneous intracranial hypotension. This finding suggests that brain imaging findings as reflected by Bern scores may not reliably reflect clinical severity and should not replace clinical metrics for outcome assessment.

There is no impact of exposure measurement error on latency estimation in linear models.

Identification of the latency period for the effect of a time-varying exposure is key when assessing many environmental, nutritional, and behavioral risk factors. A pre-specified exposure metric involving an unknown latency parameter is often used in the statistical model for the exposure-disease relationship. Likelihood-based methods have been developed to estimate this latency parameter for generalized linear models but do not exist for scenarios where the exposure is measured with error, as is usually the case. Here, we explore the performance of naive estimators for both the latency parameter and the regression coefficients, which ignore exposure measurement error, assuming a linear measurement error model. We prove that, in many scenarios under this general measurement error setting, the least squares estimator for the latency parameter remains consistent, while the regression coefficient estimates are inconsistent as has previously been found in standard measurement error models where the primary disease model does not involve a latency parameter. Conditions under which this result holds are generalized to a wide class of covariance structures and mean functions. The findings are illustrated in a study of body mass index in relation to physical activity in the Health Professionals Follow-Up Study.

In prostate cancer needle biopsies, detections of PTEN loss by fluorescence in situ hybridization (FISH) and by immunohistochemistry (IHC) are concordant and show consistent association with upgrading.

The prognostic value of phosphatase and tensin homolog (PTEN) loss in prostate cancer has primarily been evaluated by either fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC). Previously, we found that PTEN loss by IHC was associated with increased risk of upgrading from biopsy (Gleason 3 + 3) to prostatectomy (Gleason 7+). Now, using an evaluable subset of 111 patients with adjacent biopsy sections, we analyzed the association between PTEN deletion in cancer and the odds of upgrading by a highly sensitive and specific four-color FISH assay. We also compared the concordance of PTEN loss by IHC and PTEN deletion by FISH. PTEN deletion was found in 27 % (12/45) of upgraded cases compared with 11 % (7/66) of controls (P = 0.03). Cancers with PTEN deletions were more likely to be upgraded than those without deletions (adjusting for age odds ratio = 3.40, 95 % confidence interval 1.14-10.11). With respect to concordance, of 93 biopsies with PTEN protein detected by IHC, 89 (96 %) had no PTEN deletion by FISH, and of 18 biopsies without PTEN protein by IHC, 15 had homozygous or hemizygous PTEN deletion by FISH. Only 4 biopsies of the 93 (4 %) with PTEN protein intact had PTEN deletion by FISH. When the regions of uncertainty in these biopsies were systematically studied by FISH, intra-tumoral variation of PTEN deletion was found, which could account for variation in immunoreactivity. Thus, FISH provides a different approach to determining PTEN loss when IHC is uncertain. Both FISH and IHC are concordant, showing consistent positive associations between PTEN loss and upgrading.

Intraprostatic inflammation is positively associated with serum PSA in men with PSA <4 ng ml(-1), normal DRE and negative for prostate cancer.

BACKGROUND: Biopsies performed for elevated serum PSA often show inflammatory infiltrates. However, the influence of intraprostatic inflammation on serum PSA in men without biopsy indication and negative for prostate cancer has not been described in detail. METHODS: We studied 224 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT) who underwent end-of-study biopsy per trial protocol, had PSA <4 ng ml(-1), normal digital rectal examination and a biopsy negative for cancer. We analyzed data from hematoxylin and eosin-stained slides containing a mean of three biopsy cores. Inflammation measures included the extent (percentage of tissue area with inflammation) and intensity (product of scores for extent and grade) of total, acute and chronic inflammation in the entire tissue area examined, and by tissue compartment. We calculated median measures of inflammation by prebiopsy serum PSA tertile (>0 to ≤0.8, >0.8 to ≤1.5 and >1.5 to <4.0 ng ml(-1)). We estimated the association between percentage of tissue area with inflammation and natural logarithm of PSA using linear regression adjusting for age at biopsy. RESULTS: Median percentage of tissue area with inflammation increased from 2 to 5 to 9.5% across PSA tertiles (P-trend <0.0001). For every 5% increase in tissue area with inflammation, log PSA increased by 0.061 ng ml(-1) (P=0.0002). Median extent and intensity scores increased across PSA tertiles in luminal and intraepithelial compartments for acute inflammation and in stromal and intraepithelial compartments for chronic inflammation (all P-trend ≤0.05). CONCLUSIONS: In men without clinical suspicion of prostate cancer, greater overall inflammation, luminal and intraepithelial acute inflammation and stromal and intraepithelial chronic inflammation were associated with higher serum PSA.

Association of variants in genes related to the immune response and obesity with BPH in CLUE II.

BACKGROUND: Chronic inflammation and obesity may contribute to the genesis or progression of BPH and BPH-associated lower urinary tract symptoms (LUTS). The influence of variants in genes related to these states on BPH has not been studied extensively. Thus, we evaluated the association of 17 single-nucleotide polymorphisms (SNPs) in immune response genes (IL1B, IL6, IL8, IL10, TNF, CRP, TLR4 and RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG and TCF7L2), with BPH. METHODS: BPH cases (N = 568) and age-frequency matched controls (N=568) were selected from among adult male CLUE II cohort participants who responded in 2000 to a mailed questionnaire. BPH was defined as BPH surgery, use of BPH medications or symptomatic BPH (American Urological Association Symptom Index Score ⩾ 15). Controls were men who had not had BPH surgery, did not use BPH medications and whose symptom score was ⩽ 7. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. RESULTS: None of the candidate SNPs was statistically significantly associated with BPH. However, we could not rule out possible weak associations for CRP rs1205 (1082C>T), ADIPOQ rs1501299 (276C>A), PPARG rs1801282 (-49C>G) and TCF7L2 rs7903146 (47833T>C). After summing risk alleles, men with ⩾ 4 had an increased BPH risk compared with those with ⩽ 1 (OR, 1.78; 95% CI, 1.10-2.89; P(trend) = 0.006). CONCLUSIONS: SNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH.

Masking of exercise-induced ST-segment depression by rate-dependent left-axis deviation.

An unexpected high incidence of false negative ST-segment responses to exercise was previously reported for patients with coronary artery disease and abnormal left-axis deviation on their resting electrocardiograms. In the case presented, an exercise-induced, "ischemia" ST-segment depression was masked with the onset of rate-dependent left-axis deviation. The state of the base-line electrocardiogram is an important but often overlooked factor in assessing the incidence of false negative and false positive ST-segment responses to exercise.

Detection of left ventricular aneurysms by cross-sectional echocardiography.

Real-time cross-sectional echocardiographic studies of the left ventricle were performed in 31 consecutive patients with angiographically proven left ventricular aneurysms (group I). In each of these patients the presence and location of the aneurysm was visualized by the cross-sectional echocardiography. In four patients discrepancy in the extent of the aneurysm was noted due either to failure of the cross-sectional technique to visualize the entire anterior wall of the ventricle (3) or failure of the single plane angiogram to adequately define the lateral extent of the aneurysm (1). Ventricular shape and contraction sequence in patients with aneurysms were compared with similar patterns in 20 patients with normal left ventricles (group II), and 20 patients with ischemic heart disease and localized ventricular dysfunction without aneurysm formation (group III). Other noninvasive methods for detecting aneurysms (including physical examination, chest roentgenography, electrocardiography, and M-mode echocardiography) were also evaluated in the aneurysm group. This report suggests that cross-sectional echocardiography is a useful method for detecting ventricular aneurysms noninvasively.

M-mode echocardiography in the evaluation of patients for aneurysmectomy.

In order to determine whether echocardiography could be useful in predicting surgical mortality of aneurysmectomy, preoperative condensed M-mode echocardiographic scans were taken from both mid (standard position) and low (nearer apex) intercostal spaces and/or from the subxiphoid area in eighteen patients who were sent to surgery for aneurysmectomy. Eleven of the eighteen patients survived aneurysmectomy. All eleven had mid left ventricular dimensions less than 3.3 cm/m2 and low dimensions of 3.8 cm/m2 or less. Of the seven patients who died, the mid and low left ventricular dimensions exceeded 3.3 cm/m2 and 3.8 cm/m2, respectively, with one exception. The combination of abnormal mitral valve closure, a dilated mid dimension and lack of normal motion in opposing wall segments was only seen in six nonsurvivors. Echocardiography can provide information concerning the state of the left ventricle in patients with ventricular aneurysms and these findings may be helpful in predicting surgical mortality for aneurysmectomy.

Left axis deviation and left anterior hemiblock among 8,000 Japanese-American men.

Electrocardiographic patterns of left axis deviation and left anterior hemiblock, defined by a frontal plane QRS axis of minus 30 degrees to minus 44 degrees and minus 45 degrees to minus 90 degrees, respectively, with normal QRS duration, were found to be fairly common (2.6 and 1.5 percent, respectively) in a community population of 8,000 Japanese-American men aged 45 to 69 years. More than 60 percent of men with these electrocardiographic patterns had no other cardiovascular abnormalities, and the incidence of fatal or nonfatal coronary heart disease and stroke in this group during observation periods of 3 to 6 years was not significantly different from that of control normal men. A significant association was found between these electrocardiographic patterns and the prevalence of hypertension, myocardial infarction and stroke. However, the association of myocardial infarction with left anterior hemiblock appeared to be coincidental and was attributed largely to the similarity of the electrocardiographic manifestations of left anterior hemiblock and inferior wall myocardial infarction. Men with left axis deviation were fatter and had higher blood pressure than the control population. No such difference could be demonstrated for men with left anterior hemiblock although this group was significantly older than control subjects and men with left axis deviation. The results of our study suggest that there are qualitative differences between the causative mechanisms and clinical features of left axis deviation and those of left anterior hemiblock.