Estimating survival in advanced cancer: a comparison of estimates made by oncologists and patients.

PURPOSE: To compare estimates of expected survival time (EST) made by patients with advanced cancer and their oncologists. METHODS: At enrolment patients recorded their "understanding of how long you may have to live" in best-case, most-likely, and worst-case scenarios. Oncologists estimated survival time for each of their patients as the "median survival of a group of identical patients". We hypothesized that oncologists' estimates of EST would be unbiased (~ 50% longer or shorter than the observed survival time [OST]), imprecise (< 33% within 0.67 to 1.33 times OST), associated with OST, and more accurate than patients' estimates of their own survival. RESULTS: Twenty-six oncologists estimated EST for 179 patients. The median estimate of EST was 6.0 months, and the median OST was 6.2 months. Oncologists' estimates were unbiased (56% longer than OST), imprecise (27% within 0.67 to 1.33 times OST), and significantly associated with OST (HR 0.88, 95% CI 0.82 to 0.93, p < 0.01). Only 41 patients (23%) provided a numerical estimate of their survival with 107 patients (60%) responding "I don't know". The median estimate by patients for their most-likely scenario was 12 months. Patient estimates of their most-likely scenario were less precise (17% within 0.67 to 1.33 times OST) and more likely to overestimate survival (85% longer than OST) than oncologist estimates. CONCLUSION: Oncologists' estimates were unbiased and significantly associated with survival. Most patients with advanced cancer did not know their EST or overestimated their survival time compared to their oncologist, highlighting the need for improved prognosis communication training. Trial registration ACTRN1261300128871.

Neuromedin U receptor 2 knockdown in the paraventricular nucleus modifies behavioral responses to obesogenic high-fat food and leads to increased body weight.

Neuromedin U (NMU) is a highly conserved neuropeptide which regulates food intake and body weight. Transgenic mice lacking NMU are hyperphagic and obese, making NMU a novel target for understanding and treating obesity. Neuromedin U receptor 2 (NMUR2) is a high-affinity receptor for NMU found in discrete regions of the central nervous system, in particular the paraventricular nucleus of the hypothalamus (PVN), where it may be responsible for mediating the anorectic effects of NMU. We hypothesized that selective knock down of NMUR2 in the PVN of rats would increase their sensitivity to the reinforcing properties of food resulting in increased intake and preference for high-fat obesogenic food. To this end, we used viral-mediated RNAi to selectively knock down NMUR2 gene expression in the PVN. In rats fed a standard chow, NMUR2 knockdown produced no significant effect on food intake or body weight. However, when the same rats were fed a high-fat diet (45% fat), they consumed significantly more food, gained more body weight, and had increased feed efficiency relative to controls. Furthermore, NMUR2 knockdown rats demonstrated significantly greater binge-type food consumption of the high-fat diet and showed a greater preference for higher-fat food. These results demonstrate that NMUR2 signaling in the PVN regulates consumption and preference for high-fat foods without disrupting feeding behavior associated with non-obesogenic standard chow.

The successful use of cardiopulmonary support for a transected bronchus.

A 20-year-old male was involved in a motor vehicle accident and computed tomography revealed a completely transected right mainstem bronchus. An Emergency Department (ED) right anterior thoracotomy was necessary soon after arrival at our institution secondary to acute desaturation that was unresponsive to ventilator and chest tube management. This allowed direct intubation and ventilation of the right middle and lower lobes directly through the thoracotomy incision, which stabilized the patient for transport to the operating room. Once there, percutaneous cardiopulmonary support (CPS) was initiated to allow primary surgical repair of the transected bronchus. Post surgery, the patient was transported to the surgical intensive care unit on CPS which he required for an additional two days. The patient eventually did well and was discharged home. To our knowledge this is the first successful reported case of using the Avalon Elite dual lumen veno-venous cannula for CPS in a patient with complete right main-stem bronchus transection and bilateral pulmonary contusions.

Association of K121Q polymorphism in ENPP1 (PC-1) with BMI in Caucasian and African-American adults.

OBJECTIVE: To test for association of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) K121Q polymorphism with body mass index (BMI) and diabetes in a large sample of Caucasians and African-Americans by selectively genotyping individuals at the extremes of the phenotypic distribution. SUBJECTS: Subsets comprising the extremes of the BMI distribution (10th-20th and above the 90th BMI percentile for Caucasians and between the 10th-30th and above the 80th percentile for African-Americans) from a group of 10,260 Caucasian and 2268 African-American adults participating in New York Cancer Project were studied. METHODS: Subjects were genotyped for the ENPP1 K121Q polymorphism by pyrosequencing and tested for association with BMI and diabetes by regression analysis. RESULTS: Regression analysis with BMI as the dependent variable demonstrated a significant association (P = 0.02) of genotype at K121Q with BMI, with no significant race-by-genotype interaction (P = 0.30). Compared with Q/Q or Q/K individuals, the K/K individuals had a BMI approximately 1.3 kg/m2 higher, without effects of age, gender or race. By logistic regression analysis, the K121Q alleles had no significant effect on diabetes status (P = 0.37) in obese subjects. CONCLUSION: In both Caucasians and African-Americans, the K121 polymorphism in ENPP1 was associated with increased BMI, but not with diabetes.

Screening programs to identify children at risk for diabetes mellitus: psychological impact on children and parents.

Screening programs to identify persons atrisk for diabetes mellitus (DM), before disease onset, are considered essential to understanding the natural history of the disease and for prevention program development. However, screening programs are complicated by imprecise markers of disease risk, the absence of a known effective prevention method, the use of children, and a wide variety of psychological, social, and educational challenges. Research relevant to four issues is presented: (1) parent and child anxiety in response to at-risk notification as well as how participants cope with this news; (2) accuracy of mothers' understanding of their babies' risk status; (3) predictors of participant recruitment and retention in longitudinal studies of this type; and (4) protocol compliance in prevention trials for type 1 DM. Integration of behavioral research into screening and prevention trials would help address the ethical concerns raised by such trials and improve their scientific quality.

Thymoma: update for the new millennium.

Thymomas are relatively common tumors of the anterior superior mediastinum. They are usually relatively slowly growing tumors and their prognosis depends on the macroscopic and microscopic invasion of surrounding tissues. Surgery is the mainstay treatment of thymomas, and complete resection represents one of the most important prognostic factors in this disease. Other important prognostic indicators include the tumor stage and size and the presence of symptoms. Postoperative radiotherapy is indicated in tumors with invasion of surrounding tissues, even if resection was radical, since it improves local control and survival. Cytotoxic chemotherapy has been employed in several relatively small phase II studies and in advanced disease has been demonstrated to produce a 50%-80% objective response rate. Neoadjuvant cytotoxic chemotherapy and/or external beam radiotherapy has been used with some success in patients with tumors which are not readily resectable. Novel antiproliferative systemic agents, with both cytotoxic and cytostatic mechanisms of action, are being tested in ongoing prospective clinical trials.

Use of the Extensible Stylesheet Language (XSL) for medical data transformation.

Recently, the Extensible Markup Language (XML) has received growing attention as a simple but flexible mechanism to represent medical data. As XML-based markups become more common there will be an increasing need to transform data stored in one XML markup into another markup. The Extensible Stylesheet Language (XSL) is a stylesheet language for XML. Development of a new mammography reporting system created a need to convert XML output from the MEDLee natural language processing system into a format suitable for cross-patient reporting. This paper examines the capability of XSL as a rule specification language that supports the medical XML data transformation. A set of nine relevant transformations was identified: Filtering, Substitution, Specification, Aggregation, Merging, Splitting, Transposition, Push-down and Pull-up. XSL-based methods for implementing these transformations are presented. The strengths and limitations of XSL are discussed in the context of XML medical data transformation.

Use of an Objective Structured Clinical Examination (OSCE) for the assessment of physician performance in the ultrasound evaluation of trauma.

BACKGROUND: A reliable means of assessing physician competency in performing ultrasound (US) is critical for training and credentialing. Objective Structured Clinical Examinations (OSCE) have been used successfully to assess clinical competency in other areas of surgical education but have not been applied previously to trauma ultrasound training. The objectives of this study were to assess physician performance in the focused abdominal sonography in trauma (FAST) examination by using a specifically designed OSCE, and to determine whether the OSCE detects differences in two determinants of competency (knowledge acquisition and clinical interpretation skills). METHODS: Eighty-two physicians in surgery (n = 49) and emergency medicine (n = 33) at a Level I trauma center were evaluated. All participated in a FAST course consisting of didactic sessions on US physics, indications, and technique, FAST examination videos, and a hands-on session with human models. The OSCE consisted of two parts: written examination that assessed factual knowledge, and videotape of real-time US examinations that assessed interpretation skills. The OSCE was administered before and after the FAST course. RESULTS: Significant improvements in postcourse OSCE scores were observed for factual knowledge (52.5 +/- 2.0 vs. 87.5 +/- 1.1, p < 0.001) and interpretation skills (27.2 +/- 1.4 vs. 62.9 +/- 1.3, p < 0.007). Scores for US interpretation were significantly lower than those for factual knowledge at both precourse (27.2 +/- 1.4 vs. 52.5 - 2.0, p < 0.001) and postcourse (62.9 +/- 1.3 vs. 87.5 +/- 1.1, p < 0.01). No performance differences were observed between surgeons and emergency medicine physicians and no effect of training level on test scores was observed. CONCLUSION: Knowledge acquisition and US interpretation skills can be assessed reliably with a specifically designed OSCE. Although both skills improved after participation in a FAST course, US interpretation scores were consistently lower than those for factual knowledge. This study supports the use of the objective structured clinical examination in both the design of ultrasound teaching programs and the assessment of physician competency.

Clinical and scientific importance of source control in abdominal infections: summary of a symposium.

In May 1997, a panel of surgeon-investigators met to discuss the clinical importance and research implications of controlling the source of abdominal infections. It was concluded that source control is critical to therapeutic success and that antimicrobial therapy and other adjunctive interventions will fail if the source of infection is not controlled by resection, exteriorization or other means. The panelists presented different definitions of source control, depending on the scientific purpose of the definition. All participants agreed that failure to consider the adequacy of source control of infection has limited the value of most clinical trials of therapeutic anti-infective agents. Besides recognizing source control as an essential goal of patient care, the panelists emphasized the need for further investigative work to define, record and stratify the adequacy of source control in clinical trials of therapeutic agents for abdominal infections.

Management of major tracheobronchial injuries: a 28-year experience.

BACKGROUND: Tracheobronchial injuries are rare but potentially life threatening. Their successful diagnosis and treatment often require a high level of suspicion and surgical repairs unique to the given injury. METHODS: We reviewed our experience with 32 patients with tracheobronchial injuries treated over the past 28 years. RESULTS: Forty-one percent (13/32) of the injuries were due to blunt trauma and 59% (19/32), to penetrating trauma. Most penetrating injuries were located in the cervical trachea (74%), whereas blunt injuries were more commonly located close to the carina (62%). Fifty-nine percent of the patients required urgent measures to secure the airway. Penetrating injuries were usually diagnosed by clinical findings or at surgical exploration. The diagnosis of blunt injuries was more difficult and required a high index of suspicion and the liberal use of bronchoscopy. The majority of the injuries were repaired primarily using techniques specific to the injury, and most patients returned to their normal activity soon after discharge. CONCLUSIONS: A high level of suspicion and the liberal use of bronchoscopy are important in the diagnosis of tracheobronchial injury. A tailored surgical approach is often necessary for definitive repair.

Mechanism of lethal proarrhythmia observed in the Cardiac Arrhythmia Suppression Trial: role of adrenergic modulation of drug binding.

A variety of recent in vivo studies have sought to clarify the mechanism underlying the proarrhythmic response of flecainide in the Cardiac Arrhythmia Suppression Trial (CAST). Increased inducibility of relatively stable ventricular arrhythmias in subacute and chronic postinfarction models has been universally observed. The arrhythmogenesis has been explained in part by drug induced modulation of anisotropic conduction in persistently ischemic tissue, increased durations of vulnerable windows, enhanced generation of unidirectional block with the introduction of extrastimuli, variability of repolarization within the ventricular wall, and the creation of stable reentrant circuits with narrow central zones of propagation. While these data explain arrhythmogenesis in general, malignant ventricular arrhythmia capable of producing the excess sudden or arrhythmic death mortality in the CAST trial have not been universally observed, nor have the proported beneficial effects of beta-blockade seen in the CAST trial and other studies been explained. Additional studies examining the adrenergic modulation of flecainide binding have shown reversal of flecainide effects in normal tissue, but paradoxical amplification of flecainide induced conduction slowing in depolarized tissue. This variable effect in normal versus abnormal tissue produces significant dispersions of conduction with an expected increased propensity for conduction failure in response to ectopy, increased liminal length for impulse propagation, enhanced vulnerability to premature extrastimuli, and completed reentrant circuits in regions of depressed membrane potentials. This, along with the decrease in action potential duration and accompanying refractoriness in the setting of adrenergic modulation may favor more malignant double wavelet or unstable ventricular arrhythmias.

Dual-inflow great vessel aneurysm: delayed presentation after penetrating trauma.

Aneurysms constitute uncommon sequelae of injuries to the thoracic outlet. Most such aneurysms are secondary to blunt trauma and usually involve the great vessels at their take-off from the aortic arch. Penetrating injuries are more often identified in the more distal vessels and only very rarely present as pseudoaneurysms. Reported here is a single case of a chronic posttraumatic pseudoaneurysm arising from both the right common carotid artery and the right subclavian artery. The workup and surgical approach provide practical lessons, complemented with illustrations that aid in the understanding of the case. It is an unusual case because of the dual-inflow nature of the aneurysm.

Essential fatty acid deficiency and predisposition to lung disease in cystic fibrosis.

UNLABELLED: Essential fatty acid (EFA) deficiency is a predisposing factor for pulmonary infection with Staphylococcus aureus and Pseudomonas aeruginosa, the two major pathogenic microorganisms in cystic fibrosis (CF). OBJECTIVE: The goal of this study was to investigate the essential fatty acid status of CF patients from infancy to 20 years old. MATERIALS AND METHODS: Plasma fatty acid profiles for phospholipid (PL) were determined for cord (n = 6), 4 months (n = 40), 16 months (n = 25), 3 y (n = 8), 5-10 y (n = 10), and 10-20 y (n = 10) aged CF patients and compared to their respective control; cord (n = 22), 1-36 months (n = 38) and adult (n = 100). Significance was established by Student's t-test (p < 0.05). RESULTS: The plasma PL fatty acid profile for all CF patients, except cord, revealed consistent deficiency in omega 3 and omega 6 EFAs. These deficiencies were most marked at infancy and more pronounced for patients with meconium ileus. CONCLUSIONS AND RELEVANCE: EFA deficiency may contribute to the predisposition of CF infants to develop respiratory disease and to the excess cytotoxic activity found in bronchoalveolar lavage fluid at 2 months of age in the majority of screened infants.

Penetrating intrapericardial wounds: clinical experience with a surgical protocol.

BACKGROUND: From 1972 to 1977, a treatment protocol was developed at our institution for patients with suspected penetrating intrapericardial wounds. It consists of immediate transport to the operating room, pericardial decompression by subxiphoid pericardial window under local or light general anesthesia in patients in stable condition, and median sternotomy and operative repair with limited use of cardiopulmonary bypass. METHODS: The records of 79 consecutive patients with acute penetrating intrapericardial injury who underwent operation from March 1978 to July 1991 were reviewed. There were 59 patients (75%) with stab wounds and 20 (25%) with gunshot wounds. Wound location was as follows: right ventricle, 33 (42%); left ventricle, 28 (35%); multiple sites, 8 (10%); atrium, 5 (6%); and great vessels, 5 (6%). RESULTS: Subxiphoid pericardial window was performed under local or light general anesthesia in 53 patients (67%). Cardiopulmonary bypass was required in only 4 patients. Overall mortality was 6%. CONCLUSION: Approach to a trauma victim must be systematic. We believe one treatment protocol for patients with suspected penetrating intrapericardial wounds is effective.

Homograft patch repair for hemorrhagic mediastinitis.

Hemorrhage from the heart and great vessels is a potentially lethal complication of post-sternotomy mediastinitis. We report 2 cases in which a cryopreserved descending thoracic aortic homograft was used successfully to repair defects of the ascending aorta and right ventricle in the setting of active mediastinal infection. An overview of mediastinitis and management strategies for life-threatening mediastinal bleeding is included.

The relationship between faculty ward evaluations, OSCE, and ABSITE as measures of surgical intern performance.

BACKGROUND: This study determined the degree to which ward evaluations, the American Board of Surgery In-Training Examination (ABSITE), and an Objective Structured Clinical Examination (OSCE) provide equivalent information about intern performance. METHODS: Twenty-two general surgery interns completed both the ABSITE and a 17-problem, 35-station OSCE. Faculty members completed several 12-item ward evaluations for each intern. Pearson product-moment correlations were employed to determine the degree of association among the various evaluation measures. RESULTS: The total OSCE score correlated with both the total ABSITE score and the overall ward evaluations, but the latter two measures did not correlate with each other. The ward evaluations identified the performance of 1 of the 22 interns (5%) as deficient, the ABSITE identified 9 (41%) as deficient in knowledge, and the OSCE 8 (36%). CONCLUSIONS: In the future, performance-based testing methods such as the OSCE should become more important as an evaluative parameter in assessing the clinical performance of postgraduate surgical trainees.

Transesophageal echocardiography in the diagnosis of traumatic rupture of the aorta.

BACKGROUND: Rupture of the aorta is a major cause of death after motor vehicle accidents. Survival depends on early diagnosis, and emergency aortography is the standard imaging method. Although transesophageal echocardiography is noninvasive and can provide high-resolution images of the aorta, information about its value in patients with trauma is limited. We conducted this study to assess prospectively the value of transesophageal echocardiography in the emergency evaluation of patients at risk for aortic injury. METHODS: Transesophageal echocardiography of the aorta was attempted in 101 patients admitted to the emergency room with a diagnosis of possible traumatic rupture of the aorta. Echocardiography and aortography personnel were notified simultaneously of the arrival of the patient, and the two tests were performed sequentially by operators who were blinded to the results of the other test. The sensitivity and specificity of transesophageal echocardiography were calculated on the basis of the results of aortography of the arch, surgery, or autopsy. RESULTS: Transesophageal echocardiography was attempted in 101 patients. The study was successfully performed in 93 patients but could not be completed in 8 because of lack of cooperation on the part of the patient (7 patients) or maxillofacial trauma (1 patient). Despite a high injury-severity score (mean, 29.6), transesophageal echocardiography was performed without complications, and within a mean (+/- SD) of 29 +/- 12 minutes. Eleven of the 93 studies (12 percent) demonstrated rupture of the aorta near the isthmus. The findings were confirmed in 10 of the 11 patients by aortography (9 patients), surgery (9 patients), or autopsy (1 patient), yielding a sensitivity of 100 percent and specificity of 98 percent for the detection of injury to the aorta. There was one false positive echocardiogram. CONCLUSIONS: Transesophageal echocardiography is a highly sensitive and specific method of detecting injury to the thoracic aorta. This technique can be used safely and quickly in critically injured patients with suspected traumatic rupture of the aorta and compares favorably with arch aortography.

Assessing surgical residents' and medical students' interpersonal skills.

Effective physician-patient interaction is an important part of surgical practice. This study had three goals: (1) to measure the interpersonal skills (IS) of surgical students and residents in structured clinical settings and to determine the reliability of such measurements; (2) to determine the relationship of IS to clinical performance; and (3) to determine the impact of level of training on IS. Twenty third-year medical students and 30 junior-level interns (23 PGY-1s, 7 PGY-2s) interacted with nine actual or simulated patients as part of an objective structured clinical examination. Using a global rating scale, faculty graded both the IS and the organizational skills of the candidates. A two-way analysis of variance indicated significant differences among the three groups of trainees (P = 0.0002) and among the IS scores for each of the nine patient problems (P < 0.0001). Both the PGY-2s and the medical students exhibited significantly better interpersonal skills than did the PGY-1s. The IS scores correlated significantly with the data gathering scores, the data interpretation scores, and the organizational scores. We conclude that faculty measurement of IS is moderately reliable even when a simple global rating scale is used. Overall IS scores were rather poor, particularly in the PGY-1 group. IS were highly correlated with overall objective clinical performance.