CT screening for lung cancer

The Early Lung Cancer Action Project (ELCAP) recently demonstrated that earlier diagnosis of lung cancer can be achieved with CT, and these results have led to considerable demand for CT screening. The advisability of screening seems obvious, as screening has been shown to provide for lung cancer treatment at a relatively early stage, leading to a better chance to avert death from lung cancer than when treatment is prompted by symptoms and/or signs. There are, however, countervailing ideas that CT lung cancer screening has not yet been demonstrated to 'save lives.' Further, it has been stated that CT screening has a notable problem of "overdiagnosis," meaning that screening finds lesions that are not life threatening, leading to unnecessary surgery. These concerns have led to the argument that assessing 'lives saved,' as well as the effects of overdiagnosis, can only be achieved with a randomized, controlled trial comparing CT screening with no screening, using a mortality endpoint. To this end, the National Lung Screening Trial (NLST) has been funded. This randomized, controlled trial is the most expensive screening study ever proposed. It compares CT screening with chest X-ray screening, and its designers envision that it will provide an answer about the benefit of CT screening, or lack thereof, in about 10 years. We do not question the value of the randomized design of 'treatment' trials for comparing competing interventions (treatments), but we have serious concerns about the use of randomization in the evaluation of a diagnostic test, such as CT. We feel that randomization is not necessary for evaluating a diagnostic test and may generate misleading results. Rather, we feel that the desired information is how often and how early is the disease diagnosed using that test. The purpose of this article is to raise the general level of concern about the underpinnings of such randomized 'screening' trials, and to convey some of the evidence that led to our pessimism about the NLST.     

Effects of simultaneous insertion of 66 plunge needle electrodes on myocardial activation, function, and structure

Transmural recordings using plunge needle electrodes are useful in mapping ventricular tachyarrhythmia, but they interfere with activation sequences or damage the myocardium. This study evaluated the effects of insertion of 66 transmural needles on myocardial activation, structure, and function. Epicardial maps were performed at thoracotomy using a 40-electrode plaque in five mongrel dogs. Sixty-six transmural plunge needles were introduced into the anterior aspect of the septum and left ventricle. Transmural maps of unipolar electrograms were recorded every 15 minutes via 124 electrodes over a 2-hour period. Epicardial maps were repeated after the needles were removed. All recordings were performed during sinus rhythm and ventricular pacing at 300- and 200-ms cycle lengths. Gated heart pool studies were performed preoperatively and 2 weeks after thoracotomy. Programmed ventricular stimulation was performed 2 weeks after thoracotomy. In total, 15,996 electrograms were analyzed. Maximum negative dV/dt of each electrogram and the activation time at each electrode did not change significantly over the 2 hours of needle insertion. After removal of the needles, epicardial maps were unchanged compared to before needle insertion. Mean left ventricular ejection fraction 2 weeks after needle insertion was 59% versus 58% before needle insertion (P=0.9). No dogs had inducible ventricular tachycardia. Histology showed contraction bands of 0.8-mm diameter adjacent to the needle tracks but no scarring. Insertion of 66 closely spaced plunge needles did not distort epicardial or transmural maps. Multiple needles did not result in myocardial scarring, left ventricular dysfunction, or predispose to ventricular tachycardia.     

Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1)

Large clonal expansions of peripheral CD8+ T cells carrying receptors for single epitopes of CMV and EBV are common in the elderly and may be associated with an immune risk phenotype predicting mortality. Here we show that the frequency of CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1), a marker of cells unable to undergo further clonal expansion, was markedly elevated in CD8+ T cells from old donors. Moreover, tetramer staining revealed that the elevated frequency of CMV-specific CD8+ T cells in the elderly was due to an accumulation of cells bearing this dominant negative receptor. The fraction of CMV-specific T cells able to secrete interferon-gamma after specific antigenic stimulation was significantly lower in the elderly than in the young, although the total number of functional cells was comparable. Therefore, the majority of the clonally expanded virus-specific CD8+ cells in the elderly was dysfunctional. Thus, T cell responses are altered in the aged by an accumulation of replicatively senescent dysfunctional T cells carrying receptors for persistent herpes viruses. The presence of clonal expansions of such virus-specific cells may shrink the available repertoire for other antigens and contribute to the increased incidence of infectious disease in the elderly.     

Quantitation of basal dyssynchrony and acute resynchronization from left or biventricular pacing by novel echo-contrast variability imaging

OBJECTIVES: This study sought to test a novel echocardiographic method based on contrast variability imaging (CVI), to quantify cardiac dyssynchrony and magnitude of resynchronization achieved by left ventricular (LV) and biventricular (BiV) pacing therapy. BACKGROUND: Left ventricular or BiV pacing is a promising new therapy for patients with heart failure and intraventricular conduction delay. However, precise quantitation of the extent of resynchronization achieved remains scant. METHODS: Ten patients treated with BiV or LV pacing therapy were studied. Echo-contrast was infused slowly, and gated images were acquired before and during contrast appearance. The temporally normalized variance derived from 30 to 50 sequential beats was determined at each pixel to yield the CVI image-displaying improved wall delineation. Systolic regional fractional area of radial sectors was calculated with active and temporarily suspended (AAI) pacing. All analyses were performed blinded to both patient and treatment. RESULTS: Pacing increased septal inward motion from -20.4 +/- 9.6% to -30.5 +/- 14.0%, whereas lateral wall motion occurred earlier with no net magnitude change. Both spatial and temporal dyssynchrony in the LV declined nearly 40% with LV or BiV pacing (p < or = 0.001), and this correlated with increasing ejection fraction (31% to 39%; p < 0.02; p < 0.004 for correlation with dyssynchrony). CONCLUSIONS: The new imaging and regional dyssynchrony analysis methods provide quantitative assessment of resynchronization analogous to that previously obtained only by tagged magnetic resonance imaging. This could provide a useful noninvasive method for both identifying candidates and following long-term therapy.     

The prosecution of sexual assault cases: correlation with forensic evidence.

STUDY OBJECTIVE: We sought to determine the association between historical and physical evidence with judicial outcome in sexual assault cases. METHODS: A population-based, retrospective review of forensic evidence was conducted for all sexual assault cases reported in Duval County, FL, during a 2-year period. Variables examined included age, race of victim, evidence of trauma (body, genital, or both), presence of spermatozoa at the time of the forensic examination, weapon use, and whether the victim knew the assailant. In cases in which an arrest was made, logistic regression was used to estimate the strength of association with the outcome of conviction in sexual assault cases. RESULTS: During the study period, 821 sexual assaults were reported, and 801 forensic examinations were performed. The victims were predominantly female (776; 97%), with 409 (51%) being black, 376 (47%) white, and 16 (2%) other minorities. A suspect was identified in 355 (44%) of the 801 cases for which a sexual assault forensic examination was conducted. No suspect was identified in 446 (56%) of these cases. There were 271 arrests made. The police did not have enough evidence to arrest a suspect after detention in 84 cases. For those cases in which a suspect was arrested, 153 had charges dropped, 89 were found guilty, 2 were found not guilty, and 27 cases were still pending or the files were sealed and unavailable for review. There was evidence of trauma in 202 (57%) of the examinations, and spermatozoa were found at the time of the forensic examination in 110 (31%) of the cases in which a suspect was identified. Logistic regression found that victims aged younger than 18 years, the presence of trauma, and the use of a weapon by the assailant were significantly associated with successful prosecution. There was a trend toward conviction if the victim was white. CONCLUSION: Emergency physicians have an obligation to provide care for victims of sexual assault cases. This care includes a possible legal defense. To that end, emergency physicians should be vigilant in the documentation of the history of the event (eg, weapon use) and in the documentation of traumatic injuries because these factors can assist in a successful prosecution.     

British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections

Outcomes for invasive fungal infections have greatly improved in the past decade, and several new antifungal drugs have been or will be licensed in the next few years. Early accurate diagnosis and appropriate treatment have major impact on survival. In a 1995 survey of laboratory practice in the UK for mycology, major disparities were seen, with many laboratories not undertaking even simple diagnostic procedures. Delays in processing and inadequate procedures for handling samples, incomplete or delayed reporting of results, or a combination of these, compromise the care of patients. In randomised trials of antifungal chemotherapy, optimum treatments and good alternatives for others have been defined for some infections. High-quality care requires a multidisciplinary approach to diagnosis and management. In this review, we propose microbiology, histopathology, radiology, and clinical auditing standards, with the evidence base for each reviewed. The standards are absolutes, and, therefore, provide a straightforward basis for improving services to patients if they are all implemented.     

An assessment of the management of acute bleeding varices: a multicenter prospective member-based study

OBJECTIVE: Bleeding from esophagogastric varices is a major complication of portal hypertension. Despite recent practice guidelines for the management of bleeding esophageal or gastric varices, the widespread application of these measures by gastroenterologists has not been evaluated. The purpose of this study was to continue the concept of membership-based research within diverse practice settings by expanding the American College of Gastroenterology (ACG) GI Bleeding Registry to assess the management and outcome of acute variceal bleeding. METHODS: All ACG members (domestic and foreign) were invited to participate during the 1997 Annual Fall meeting and by mail. Data were collected over 12 months. Information obtained included physician training, practice demographics, patient demographics, disease etiology and severity, clinical presentation, medications, transfusion needs, therapy, complications, and rebleeding within 2 wk. RESULTS: A total of 93 physicians/centers (79.6% domestic, 26.9% university and affiliated, 3.2% Veterans Affairs) participated. Complete demographic data were available for 725 of the 741 patients enrolled with index bleeding. The median age of these 725 patients was 52 yr and 73.3% were male. The most common single etiology for portal hypertension was cirrhosis (94.3%). The most common causes of cirrhosis were alcohol (56.7%), hepatitis C virus (30.3%), and hepatitis B virus (10.0%). Hemodynamic instability was noted in 60.7% of the patients (22.3% tachycardic, 9.7% orthostatic, 28.7% hypotensive). Index interventions included banding (40.8%; median five bands), sclerotherapy (36.3%), combination banding/sclerotherapy (6.2%), octreotide (52.6%; median 3 days), balloon tamponade (5.5%), transjugular intrahepatic portosystemic shunt (TIPS) (6.6%), liver transplantation (1.1%), surgical shunt (0.7%), and embolization (0.1%). Transfusion of packed red blood cells, fresh frozen plasma, and platelets was given in 83.4%, 44.7%, and 24.6% of the patients with index bleeding, respectively. Median transfusion was four units of packed red blood cells, three units of fresh frozen plasma, and 1.5 units of platelets. Rebleeding occurred in 92 of the 741 patients (12.6%) at a median of 7 days (mean 11 days) and was treated by banding (18.5%; median six bands), sclerotherapy (30.4%), octreotide (63%; median 2 days), balloon tamponade (17.4%), TIPS (15.2%), and surgical shunt (3.3%). Complications from the index bleeding and rebleeding within 2 wk included ulceration (2.6%, 2.2%), aspiration (2.4%, 3.3%), medication side effects (0.8%, 0%), dysphagia (2.3%, 0%), odynophagia (2.2%,0%), encephalopathy (13%,17.4%), and hepatorenal syndrome (2.4%, 2.2%), respectively. After the index bleeding, 46.2% of patients were treated with beta-blockers and 8.2% with nitrates. The majority of patients with index bleeding had Child's B cirrhosis (61.5%). Patients presenting with recurrent bleeding had mostly Child's B (46.7%) or Child's C cirrhosis (44.6%). The overall short-term mortality after index bleeding was 12.9%. CONCLUSIONS: Acute variceal hemorrhage occurs more often in patients with Child's B and C cirrhosis. Endoscopic banding is the most common single endoscopic intervention. Adjunctive pharmacotherapy is prevalent acutely and after stabilization. Both morbidity and mortality may be lower than reported in previous studies.     

A meta-analysis of genome-wide linkage scans for hypertension: the National Heart,Lung and Blood Institute Family Blood Pressure Program

bACKGROUND: Four multicenter Networks (GenNet, GENOA, HyperGEN, SAPPHIRe) form the National Heart, Lung and Blood Institute Family Blood Pressure Program (FBPP), to search for hypertension/blood pressure (BP) genes. The networks used different family designs and targeted multiple ethnic groups, using standardized protocols and definitions. Linkage genome scans were done on samples within each network (N = 6245 relatives). METHODS: The evidence was synthesized using meta-analysis. RESULTS: Combining ethnic groups, no region reached LOD >2, but several small peaks were identified, including chromosome 2p where two other recent reports find hypertension linkage. CONCLUSIONS: No regions show uniformly large effects on BP/hypertension in all populations.