Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema.

The composite physiologic index (CPI) was derived to represent the extent of fibrosis on high-resolution computed tomography (HRCT), adjusting for emphysema in patients with idiopathic pulmonary fibrosis (IPF). We hypothesised that longitudinal change in CPI would better predict mortality than forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) or diffusing capacity of the lung for carbon monoxide (D(L,CO)) in all patients with IPF, and especially in those with combined pulmonary fibrosis and emphysema (CPFE). Cox proportional hazard models were performed on pulmonary function data from IPF patients at baseline (n = 321), 6 months (n = 211) and 12 months (n = 144). Presence of CPFE was determined by HRCT. A five-point increase in CPI over 12 months predicted subsequent mortality (HR 2.1, p = 0.004). At 12 months, a 10% relative decline in FVC, a 15% relative decline in D(L,CO) or an absolute increase in CPI of five points all discriminated median survival by 2.1 to 2.2 yrs versus patients with lesser change. Half our cohort had CPFE. In patients with moderate/severe emphysema, only a 10% decline in FEV(1) predicted mortality (HR 3.7, p = 0.046). In IPF, a five-point increase in CPI over 12 months predicts mortality similarly to relative declines of 10% in FVC or 15% in D(L,CO). For CPFE patients, change in FEV(1) was the best predictor of mortality.

Sex differences in physiological progression of idiopathic pulmonary fibrosis.

In idiopathic pulmonary fibrosis, incidence is higher in males, and females may have better survival. The aim of the present study was to determine whether the rate of increase in desaturation during serial 6-min walk testing would be greater, and survival worse, for males versus females. Serial changes in the percentage of maximum desaturation area (DA) over 1 yr were estimated using mixed models in 215 patients. DA was defined as the total area above the curve created using desaturation percentage values observed during each minute of the 6-min walk test. Multivariate Cox regression assessed survival differences. Adjusting for baseline DA, 6-min walk distance, change in 6-min walk distance over time and smoking history, the percentage of maximum DA increased by an average of 2.83 and 1.37% per month for males and females, respectively. Females demonstrated better survival overall, which was more pronounced in patients who did not desaturate below 88% on ambulation at baseline and after additionally adjusting for 6-month relative changes in DA and forced vital capacity. These data suggest that differences in disease progression contribute to, but do not completely explain, better survival of females with idiopathic pulmonary fibrosis.

Reader accuracy and confidence in diagnosing diffuse lung disease on high-resolution computed tomography of the lungs: impact of sampling frequency.

BACKGROUND: The accuracy of the number of high-resolution computed tomography (HRCT) images necessary to diagnose diffuse lung disease (DLD) is not well established. PURPOSE: To evaluate the impact of HRCT sampling frequency on reader confidence and accuracy for diagnosing DLD. MATERIAL AND METHODS: HRCT images of 100 consecutive patients with proven DLD were reviewed. They were: 48 usual interstitial pneumonia, 22 sarcoidosis, six hypersensitivity pneumonitis, five each of desquamative interstitial pneumonitis, eosinophilic granulomatosis, and lymphangioleiomyomatosis, and nine others. Inspiratory images at 1-cm increments throughout the lungs and three specified levels formed complete and limited examinations. In random order, three experts (readers 1, 2, and 3) ranked their top three diagnoses and rated confidence for their top diagnosis, independently and blinded to clinical information. RESULTS: Using the complete versus limited examinations for correct first-choice diagnosis, accuracy for reader 1 (R1) was 81% versus 80%, respectively, for reader 2 (R2) 70% versus 70%, and for reader 3 (R3) 64% versus 59%. Reader accuracy within their top three choices for complete versus limited examinations was: R1 91% versus 91% of cases, respectively, R2 84% versus 83%, and R3 79% versus 72% of cases. No statistically significant differences were found between the diagnosis methods (P=0.28 for first diagnosis and P=0.17 for top three choices). The confidence intervals for individual raters showed considerable overlap, and the point estimates are almost identical. The mean interreader agreement for complete versus limited HRCT for both top and top three diagnoses were the same (moderate and fair, respectively). The mean intrareader agreement between complete and limited HRCT for top and top three diagnoses were substantial and moderate, respectively. CONCLUSION: Overall reader accuracy and confidence in diagnosis did not significantly differ when fewer or more HRCT images were used.

High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive (n = 99) or HIV-1-seronegative (n = 32) subjects, and correlating these results with the level of circulating CD4(+) and CD8(+) T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4(+) T cell count (P = 0.02) and a higher percentage and absolute number of circulating naive (CD45RA+CD62L+) CD4(+) T cells (P < 0.04). The prevalence of an abundant thymus was especially high in younger HIV-1-seropositive adults ( 40 yr) regardless of CD4 count (P = 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease.

Focal interstitial CC chemokine receptor 7 (CCR7) expression in idiopathic interstitial pneumonia.

BACKGROUND/AIMS: Idiopathic interstitial pneumonias (IIPs) are a diverse grouping of chronic pulmonary diseases characterised by varying degrees of pulmonary fibrosis. The triggers of the fibroproliferative process in IIP remain enigmatic but recent attention has been directed towards chemokine involvement in this process. METHODS: The expression of two chemokine receptors, CCR7 and CXCR4, and their respective ligands, CCL19, CCL21, and CXCL12, were examined in surgical lung biopsies (SLBs) from patients with IIP. Transcript and protein expression of these receptors and their ligands was compared with that detected in histologically normal margin SLBs. RESULTS: CCR7 and CXCR4 were detected by gene array and real time polymerase chain reaction analysis and CCR7, but not CXCR4, expression was significantly raised in usual interstitial pneumonia (UIP) relative to biopsies from patients diagnosed with non-specific interstitial pneumonia (NSIP) or respiratory bronchiolitis/interstitial lung disease (RBILD). CCR7 protein was expressed in interstitial areas of all upper and lower lobe UIP SLBs analysed. CCR7 expression was present in 50% of NSIP SLBs, and CCR7 was restricted to blood vessels and mononuclear cells in 75% of RBILD SLBs. Immune cell specific CXCR4 expression was seen in IIP and normal margin biopsies. CCR7 positive areas in UIP biopsies were concomitantly positive for CD45 (the leucocyte common antigen) but CCR7 positive areas in all IIP SLBs lacked the haemopoietic stem cell antigen CD34, collagen 1, and alpha smooth muscle actin. CONCLUSION: This molecular and immunohistochemical analysis showed that IIPs are associated with abnormal CCR7 transcript and protein expression.

Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function.

OBJECTIVE: To characterize immune phenotype and thymic function in HIV-1-infected adults with excellent virologic and poor immunologic responses to highly active antiretroviral therapy (HAART). METHODS: Cross-sectional study of patients with CD4 T cell rises of > or = 200 x 10(6) cells/l (CD4 responders; n = 10) or < 100 x 10(6) cells/l (poor responders; n = 12) in the first year of therapy. RESULTS: Poor responders were older than CD4 responders (46 versus 38 years; P < 0.01) and, before HAART, had higher CD4 cell counts (170 versus 35 x 106 cells/l; P = 0.11) and CD8 cell counts (780 versus 536 x 10(6) cells/l; P = 0.02). After a median of 160 weeks of therapy, CD4 responders had more circulating naive phenotype (CD45+CD62L+) CD4 cells (227 versus 44 x 10(6) cells/l; P = 0.001) and naive phenotype CD8 cells (487 versus 174 x 10(6) cells/l; P = 0.004) than did poor responders (after 130 weeks). Computed tomographic scans showed minimal thymic tissue in 11/12 poor responders and abundant tissue in 7/10 responders (P = 0.006). Poor responders had fewer CD4 cells containing T cell receptor excision circles (TREC) compared with CD4 responders (2.12 versus 27.5 x 10(6) cells/l; P = 0.004) and had shorter telomeres in CD4 cells (3.8 versus 5.3 kb; P = 0.05). Metabolic labeling studies with deuterated glucose indicated that the lower frequency of TREC-containing lymphocytes in poor responders was not caused by accelerated proliferation kinetics. CONCLUSION: Poor CD4 T cell increases observed in some patients with good virologic response to HAART may be caused by failure of thymic T cell production.

Court-mandated community outpatient treatment for persons found not guilty by reason of insanity: a five-year follow-up.

The authors conducted a 5-year follow-up study of 79 persons found not guilty by reason of insanity who were referred to and accepted for court-mandated community outpatient treatment. This was a severely mentally ill and violent group with extensive experience in both the criminal justice and mental health systems. This program was not without risks despite a readiness to revoke the patients' conditional release status when indicated; during the 5-year follow-up period, 25 (32%) were rearrested (18 [72%] for crimes of violence), 37 (47%) were hospitalized, and 38 (48%) had their conditional releases revoked. The authors believe that members of this population need social controls and long-term treatment when they are in the community.

Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival.

PURPOSE: We evaluated the risk and potential benefit of high-dose corticosteroid therapy in patients with idiopathic pulmonary fibrosis. SUBJECTS AND METHODS: We prospectively studied 41 patients with previously untreated, biopsy-proven idiopathic pulmonary fibrosis. Before treatment, we calculated clinical, radiographic, and physiologic severity-of-illness scores for each patient. We scored high-resolution computerized tomographic (CT) scans for ground glass and interstitial opacity. We determined the extent of cellular infiltration, interstitial fibrosis, desquamation, and granulation in open lung biopsy samples. Patients were monitored monthly for steroid-related side effects, response to therapy at 3 months, and mortality. RESULTS: All patients experienced at least one steroid-induced side effect. Eleven (27%) patients were nonresponders, 11 (27%) were responders, and 19 (46%) remained stable. Of the 19 patients who died during a mean (+/- SD) follow-up of 3.3 +/- 2.3 years, 8 (42%) lost weight during the initial 3 months of steroid therapy; only 3 (14%) of the 22 patients still living (P = 0.08) experienced weight loss. In a multivariate analysis, greater fibrosis (hazard ratio [HR] = 1.4 per unit increase; 95% confidence interval [CI]: 1.0 to 1.9; P = 0.03) and cellularity (RR = 1.9 per unit increase; 95% CI: 1.3 to 2.8; 3, P <0.001) in the biopsy sample and whether a patient was classified as a responder (RR = 0.4 versus nonresponder; 95% CI: 0.2 to 1.0; P = 0.05) or stable (RR = 0.2 versus nonresponder; 95% CI: 0.1 to 0.6, P <0.001) after steroid therapy were associated with mortality. CONCLUSION: Corticosteroid treatment for idiopathic pulmonary fibrosis is associated with substantial morbidity. Patients who remain stable or respond to corticosteroid therapy have better survival than those who fail to respond. Whether this difference reflects an effect of treatment or less severe disease can be determined only in a randomized trial.

Assessing dangerousness and responding appropriately: Hedlund expands the clinician's liability established by Tarasoff.

The complexities of the Tarasoff and Hedlund cases extended the liability of clinicians in situations in which patients communicate threats of harm to third parties. Because of these and other rulings, clinicians need to follow guidelines for staged responses to such threats and to document and substantiate their decisions.

The sensitivity of high-resolution CT in detecting idiopathic pulmonary fibrosis proved by open lung biopsy. A prospective study.

OBJECTIVES: To assess the sensitivity of high-resolution chest computed tomography (HRCT) in detecting idiopathic pulmonary fibrosis proved by biopsy specimen. To determine the degree of physiologic and pathologic abnormalities in patients with idiopathic pulmonary fibrosis who have a false-negative HRCT. DESIGN: Prospective 2-year study. SETTING: Tertiary care university hospital. PATIENTS: All patients with dyspnea and suspected interstitial lung disease referred to the University of Michigan for enrollment in the Idiopathic Pulmonary Fibrosis Specialized Center of Research (SCOR) protocol were included; 25 underwent open lung biopsy and formed the final study group. MEASUREMENTS: All patients underwent physiologic (pulmonary function, gas exchange, and exercise testing), radiologic (chest x-ray film and HRCT), and pathologic assessments (bronchoscopic and open lung biopsy). The results of HRCT were prospectively compared with results of standard pulmonary function tests, cardiopulmonary exercise testing, and open lung biopsy. RESULTS: Of 25 patients who had both HRCT and open lung biopsy, 3 patients (12%) had HRCTs that demonstrated no evidence of interstitial lung disease. These three patients had less severe disease based on clinical, radiographic, and physiologic (CRP) scores, gas exchange abnormalities, and pathologic scoring of open lung biopsy specimens, compared with those with an abnormal HRCT. CONCLUSION: We conclude that in the evaluation of patients with dyspnea and abnormal results of pulmonary function studies, a normal HRCT does not exclude early and clinically significant interstitial lung disease. In our patient population, physiologic testing was more sensitive than HRCT in detecting mild abnormalities in patients with idiopathic pulmonary fibrosis proved by biopsy specimen.

Impact of pre-radiology clinical years on resident performance.

In 1971, the American Board of Radiology dropped the requirement for at least one pre-radiology clinical year (PRCY) of training. However, requiring a clinical year for radiology residents remains a controversial issue. We reviewed 896 rotation evaluation forms involving 62 residents to see if a difference in performance could be detected between residents who entered training without or with at least one PRCY. Forty-five residents had no previous clinical training, whereas 17 had one or more PRCYs. No significant differences were detected in resident performance between non-PRCY and PRCY residents, nor were differences found by sex, age, presence of non-medical postgraduate degrees, or scores on the first part of the National Board of Medical Examiners. No study of PRCY versus non-PRCY residents can be adequately controlled; thus the failure to show a difference in performance must be interpreted with caution.

Augmented pulmonary IL-4 and IL-13 receptor subunit expression in idiopathic interstitial pneumonia.

BACKGROUND: Some idiopathic interstitial pneumonias (IIPs) are characterised by fibroproliferation and deposition of extracellular matrix. Because efficacious treatment options are limited, research has been directed towards understanding the cytokine networks that may affect fibroblast activation and, hence, the progression of certain IIPs. AIMS: To examine the expression of interleukin 4 (IL-4), IL-13, and their corresponding receptor subunits in the various forms of IIP and normal patient groups. METHODS: Molecular and immunohistochemical analysis of IL-4, interferon gamma (IFNgamma), IL-13, IL-4 receptor (IL-R), and IL-13 receptor subunits in surgical lung biopsies (SLBs) from 39 patients (21 usual interstitial pneumonia (UIP), six non-specific interstitial pneumonia (NSIP), eight respiratory bronchiolitic interstitial lung disease (RBILD), and five normal controls). RESULTS: Molecular analysis demonstrated that IL-13Ralpha2, IL-13Ralpha1, and IL-4Ralpha were present in a greater proportion of upper and lower lobe biopsies from patients with UIP than patients with NSIP and RBILD. Immunohistochemical analysis of patients with UIP, NSIP, and RBILD revealed interstitial staining for all three receptor subunits, whereas such staining was only seen in mononuclear cells present in normal SLBs. Fibroblastic foci in patients with UIP strongly stained for IL-4Ralpha and IL-13Ralpha2. Localised expression of IL-4Ralpha was also seen in SLBs from patients with NSIP but not in other groups. CONCLUSION: Some histological subtypes of IIP are associated with increased pulmonary expression of receptor subunits responsive to IL-4 and IL-13. These findings may be of particular importance in understanding the pathogenesis of IIP and, more importantly, may provide important novel therapeutic targets.

Can computed tomography of the chest stage lung cancer? Yes and no.

To determine the accuracy of computed tomography (CT) of the chest in the staging of lung cancer, we studied 418 patients with primary pulmonary carcinoma between 1979 and 1986. Each had a preoperative scan performed before detailed operative staging. Each CT scan was analyzed for components of the current TNM staging system. Computed tomography sensitivity and specificity for mediastinal lymph node metastasis were 84.4% and 84.1%, with corresponding positive and negative predictive accuracies of 68.7% and 92.9%, respectively. When TNM stages were derived from CT scans, only 190 of 418 (45.4%) completely agreed with operative staging. An additional 53 of 418 (12.7%) predicted the correct stage, although components of the TNM system were incorrect. In 94 of 418 scans (22.5%) CT overestimated the stage, whereas in 81 (19.4%) CT downgraded the stage. Computed tomography suggested metastatic lesions in liver, lung, adrenal gland, bone, or abdominal lymph nodes in 40 of 373 scans (10.7%); only five of 40 (12.5%) had documented metastasis. In summary, CT of the chest cannot accurately stage primary lung carcinoma according to the TNM classification. Because the negative predictive accuracy for mediastinal lymph node metastasis remains high (92.9%), invasive staging can be deferred for definitive thoracotomy when no lymphadenopathy is evident on CT. The high negative predictive accuracy for scans of the chest and upper abdomen makes CT a useful tool for exclusion of metastatic disease.

Computed tomography of the chest in the intensive care unit.

Two recent reports evaluated thoracic CT in critically ill patients. One looked at 87 patients with concurrent mobile chest radiographs and CT scans. CT provided unsuspected significant diagnostic information in 61 of the 87 patients. Examples included malpositioned or occluded chest tube, unsuspected large pleural effusion, empyema, pneumothorax, lung abscess, and pericardial effusion/thickening. In addition, two patients with prolonged adult respiratory distress syndrome and fever were shown by CT to have bronchiectasis as the likely explanation for the fever. Similar results were reported in the other series. Our experience concurs, and suggests that although chest CT is not needed in the majority of ICU patients, it is tremendously helpful in patients whose clinical course is not explained by the available information or whose chest radiographs are difficult to interpret.

How well does applicant rank order predict subsequent performance during radiology residency?

RATIONALE AND OBJECTIVES: Residency selection committees expend substantial time and resources on assessing the quality of residency applicants to derive an appropriate rank order for the National Residency Matching Program. The authors determined whether there is a relationship between the rank number or rank percentile of applicants selected for a residency training program and subsequent radiology residency performance. MATERIALS AND METHODS: Records of radiology residents completing their residency between 1991 and 1998 were reviewed. Available rank numbers and rank percentiles for each resident were compared with subsequent performance, as assessed subjectively by 4th-year radiology rotation evaluation forms and retrospective recall of four senior faculty members and objectively by numerical and percentile scores on the written portion of the American Board of Radiology (ABR) examinations. Correlation coefficients were obtained for each comparison. RESULTS: Rank number and rank percentile were not significantly correlated with 4th-year resident rotation evaluations or ABR written examination scores or percentiles. A small correlation existed between rank order and retrospective evaluation of resident performance by the four senior faculty. CONCLUSION: Applicant rank number and rank percentile do not correlate with subsequent radiology residency performance as assessed on rotation evaluation forms or the ABR written examinations.

Evaluation of competence in the interpretation of chest radiographs.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine relative rates of missed diagnoses for radiologists as a measure of competence in interpreting chest radiographs. MATERIALS AND METHODS: Cases involving differing interpretations of chest radiographs were collected from January 1994 through December 1999 by faculty (chest and nonchest radiology specialists) in an academic radiology department. A quarterly peer-review process designated cases months after the fact, and anonymously, as no miss or as class I (nondiagnosable), class II (very difficult diagnosis), class III (should be diagnosed most of time), or class IV (should almost always be diagnosed) missed diagnoses. The rates and classes of missed diagnoses were compared among chest faculty and for the nonchest radiology specialists as a group. RESULTS: Chest radiologists read 184,977 studies, and nonchest radiologists read 300,684 studies. Of these, 243 missed diagnoses were classified (classes I and II, 184 cases; class III, 50; and class IV, nine). No difference was detected in the rate of class III and IV misses among chest faculty, but nonchest faculty had significantly more class III (P = .022) and class IV misses (P = .016). CONCLUSION: Random sampling of differing interpretations can yield a relative rate of missed diagnoses for radiologists. No difference was detected in clinically important misses (ie, classes III and IV) among chest radiologists, but a statistically significantly higher rate of seemingly obvious misdiagnoses was found for nonchest specialty radiologists. Potential biases may have influenced this analysis, including disease prevalence, sampling, clinical factors, observer variability, and truth-in-diagnosis.

Identification of vertebral arteries on CT of the chest.

Knowledge of the superior mediastinal course of the vertebral arteries is important for radiologists who evaluate chest CT, particularly in the setting of trauma, when planning a percutaneous interventional procedure or for pre-operative planning. Our aim was to determine how often the vertebral arteries could be identified on chest CT studies. Contrast enhanced chest CT studies from 100 consecutive patients were reviewed, with specific attention to the vertebral arteries in the superior mediastinal and thoracic outlet regions. The left vertebral artery was identified in 85 patients and the right vertebral artery in 76 patients. Non-visualization of a vertebral artery was usually owing to proximal venous occlusion with extensive collateral vessels in the expected location of the vertebral arteries, local lymphadenopathy, poor contrast bolus technique or local beam hardening artefact. Radiologists need to alert surgeons planning resection of mass lesions in this region to the location of the vertebral arteries. It is also important to note that a vertebral artery was not identified on chest CT in 24% of patients.

Community treatment of severely mentally ill offenders under the jurisdiction of the criminal justice system: a review.

OBJECTIVE: Very large numbers of severely mentally ill persons now fall under the jurisdiction of the criminal justice system. A number of conditions are placed on those who are returned to the community, including specific ones related to treatment. This paper reviews the principles and practice of forensic outpatient mental health treatment. METHODS: MEDLINE, Psychological Abstracts, and the Index to Legal Periodicals and Books were searched from 1978, and all pertinent references were obtained. RESULTS AND CONCLUSIONS: Community treatment of severely mentally ill offenders who fall under the jurisdiction of the criminal justice system has important differences from treatment of nonoffenders, which focuses on alleviation of symptoms. Patients must comply with legal restrictions on their behavior, and treatment first addresses a patient's risk of harm to the community. Mentally ill offenders are often resistant to treatment. The mental health system may be disinclined to treat them due to their resistance and their criminal history, especially a history of violence. It is critical to identify a treatment philosophy that strikes a balance between individual rights and public safety and includes clear treatment goals, a close liaison between treatment staff and the criminal justice system, adequate structure and supervision, treatment staff who are comfortable with using authority, interventions for managing violence, incorporation of the principles of case management, appropriate and supportive living arrangements, and a recognition of the role of family members and significant others in treatment.

Enlarging pleural effusion after liver transplantation.

Ten of 42 patients who underwent liver transplantation were retrospectively found to have enlarging pleural effusions later than 3 days after transplantation. Seven of the 10 patients had subdiaphragmatic pathology, including 4 with hematomas, 1 with a biloma, and 2 with abscesses. One patient with a subphrenic abscess also had an empyema. Patients with a enlarging pleural effusion later than 3 days after transplantation should be evaluated for subdiaphragmatic pathology.

Management of the fetus with an abdominal wall defect.

Eleven fetuses with omphalocele and two with gastroschisis were diagnosed by prenatal ultrasonographic examination. Intact omphalocele was accurately distinguished from gastroschisis by detection of a membranous sac covering the herniated viscera, by liver protruding from the abdomen, and by the frequent association of major structural anomalies. Gastroschisis was characterized by the absence of these findings and the presence of bowel loops floating freely in the amniotic fluid. Nine of eleven fetuses with omphaloceles had other major malformations and did not survive. Two small omphaloceles and two gastroschises were correctly diagnosed as isolated defects, free from associated anomalies. All four underwent maternal transport and were successfully managed with good outcome. Prenatal ultrasonography allows rational decisions about perinatal management by distinguishing between omphalocele and gastroschisis and by screening for associated anatomic defects. Karyotype analysis should be a part of the prenatal workup. Most isolated defects can be followed and delivered normally near term. Accurate prenatal diagnosis allows maternal transport and in a few cases may alter the timing or mode of delivery.