Diverticula of Kommerell and aberrant subclavian arteries complicated by aneurysms.

This is a retrospective evaluation of the incidence of aberrant subclavian arteries (ASAs) and diverticula of Kommerell, as well as the occurrence and significance of associated aneurysms. Thoracic aortograms obtained during a 12.5-year period were reviewed, seeking the presence of aberrant right and left subclavian arteries (ARSAs/ALSAs), diverticula of Kommerell, and the incidence of associated aortic aneurysms. Several cases were evaluated with computed tomography concomitantly. Results were correlated with a literature review. Twenty-two ASAs were identified. Nineteen were on the right (ARSAs) and three were on the left (ALSAs). A diverticulum of Kommerell (DOK) was also present on the right in seven and on the left in three. Five of these patients had complicating aneurysms. Four of these were associated with ARSAs and their diverticula. Two were atherosclerotic; one was a limited dissection and one of uncertain etiology was ruptured. One additional aneurysm (atherosclerotic) involved an ALSA/DOK. The patient with the ruptured aneurysm died in surgery; three were managed conservatively because of concomitant disease; and one is being followed because of the small size (2.5 cm) of the aneurysm. ARSAs are relatively uncommon and ALSAs are rare. Both ARSA and ALSA are frequently associated with a DOK. Aneurysms rarely involve ASAs (with or without a DOK), but they are associated with a high mortality rate if they are not discovered before rupture. Early diagnosis plus surgical and/or endovascular management can be lifesaving.

Abdominal actinomycosis with hydronephrosis in childhood.

Two 11-year-old boys had similar clinical courses of abdominal actinomycosis complicating ruptured appendicitis and manifesting as abdominal masses causing hydronephrosis. Cure was effected by surgery and prolonged penicillin therapy.

Successful prophylaxis against Pneumocystis carinii pneumonia in HIV-infected children using smaller than recommended dosages of trimethoprim-sulfamethoxazole.

Prophylaxis against Pneumocystis carinii pneumonia (PCP) is an essential part of the management of children with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). No dose-ranging studies were ever performed; therefore, the amount of trimethoprim-sulfamethoxazole (TMP-SMX) needed to suppress PCP in children with HIV/AIDS is not known. The dose recommended by the Centers for Disease Control (CDC) has been thought to be just above the threshold needed for prevention, based on anecdotal breakthrough PCP in cancer patients who were improperly dosed. We have been giving prophylaxis based on body weight rather than surface area, and this, combined with growth of our children, has led to a large experience with dosages lower than the currently recommended 150 mg/m2. The medical records of children with HIV who met CDC guidelines for institution of PCP prophylaxis were reviewed. To ascertain the per square meter (m2) dosage each child was receiving, body surface area was calculated from height and weight measurements. Dosages were recalculated every 6 months and at each dosage change. Data regarding PCP infection, bacterial infections, and side effects of TMP-SMX were extracted. Data were compiled from 1,719.5 child-months of TMP-SMX prophylaxis, including 1,532.5 child-months below the currently recommended dose. Sixty-seven percent of our child-months were at or below two-thirds the CDC recommended dose. There were no cases of proven or suspected PCP. Incidence of other serious bacterial infections was low. Bacteremia and sepsis with Streptococcus pneumoniae was the most common proven bacterial infection, at a rate of 5.5 episodes per 100 child-years. The incidence of bacterial infection did not vary by the dose of TMP-SMX. TMP-SMX prophylaxis was well tolerated; most reactions were mild and self-limited and did not recur with re-institution of the drug. Only 6.1% of this cohort had TMP-SMX prophylaxis discontinued due to perceived toxicity. These data show that the currently recommended dose of TMP-SMX (150 mg/m2) may not be required to prevent PCP in children with HIV/AIDS. The drug is well tolerated at all dosage levels. The incidence of serious bacterial infection in this cohort of patients did not depend upon the amount of TMP-SMX prescribed. A prospective, controlled clinical trial of low-dose TMP-SMX for children with HIV infection is warranted.

Bacteremia, central catheters, and neonates: when to pull the line.

OBJECTIVES: Physicians who treat neonates who become bacteremic while dependent on central venous catheters face a serious and common dilemma. We sought 1) to evaluate the relationship between central venous catheter removal and outcome in bacteremic neonates, 2) to determine species of bacteria that are associated with an increased risk of infectious complications if the central catheter is not removed promptly, and 3) to provide evidence-based recommendations for central catheter management. METHOD: A retrospective cohort study of all neonates who had central venous access and developed bacteremia between July 1, 1995, and July 31, 1999, was conducted in the Duke University neonatal intensive care unit. RESULTS: The outcome for patients in whom the central catheter was not removed within 24 hours of organism identification was significantly worse (odds ratio = 9.8) than it was for those whose catheters were removed promptly. For patients who were infected with Staphylococcus aureus or with nonenteric Gram-negative rods, delayed removal of the central catheter was associated with complicated bacteremia. Catheter sterilization was attempted in 27 neonates who were infected with enteric Gram-negative rods; only 10 of these infants retained their catheters without infection-related complications. Infants who had 4 consecutive blood cultures that were positive for coagulase-negative staphylococcus (CoNS) were at significantly increased risk for end-organ damage and death, compared with infants who had 3 or fewer positive blood culture for CoNS (odds ratio = 29.58). CONCLUSIONS: Bacteremic infants experienced fewer infection-related complications when the central catheter was removed promptly. One positive blood culture for S aureus or a Gram-negative rod warrants central line removal in a neonate. Clinicians who are faced with a neonate who has 1 positive culture for CoNS may attempt medical management without central catheter removal, but documentation of subsequent negative blood cultures is crucial. Once a neonate has 3 positive blood cultures for CoNS, the central catheter should be removed.central line, neonate, bacteremia, bacteria, umbilical catheter, Broviac, percutaneous.

When to suspect fungal infection in neonates: A clinical comparison of Candida albicans and Candida parapsilosis fungemia with coagulase-negative staphylococcal bacteremia.

OBJECTIVES: To determine the epidemiology of candidemia in our neonatal intensive care unit; to compare risk factors, clinical presentation, and outcomes for neonates infected with Candida albicans, Candida parapsilosis, and coagulase-negative staphylococcus (CoNS); and to suggest a rational approach to empiric antifungal therapy of neonates at risk for nosocomial infection. DESIGN: Retrospective chart review of all neonatal intensive care unit patients with systemic candidiasis or CoNS infection between January 1, 1995 and July 31, 1998 at Duke University Medical Center. RESULTS: Fifty-one patients were reviewed. Nine of 19 patients infected with C parapsilosis and 5 of 15 patients infected with C albicans died of fungemia. Seventeen neonates had >2 positive cultures for CoNS obtained within 96 hours and 1 died. There was no statistically significant difference in birth weight, gestational age, or age at diagnosis between patient groups; however, candidemic patients had a sevenfold higher mortality rate. Before diagnosis, candidemic patients had greater exposure to systemic steroids, antibiotics, and catecholamine infusions. Of the 51 patients, 32 received third-generation cephalosporins in the 2 weeks before diagnosis and 19 did not. Twenty-nine of the 32 who were treated with third-generation cephalosporins subsequently developed candidemia, while candidemia occurred in only 5 of 19 patients who were not treated with cephalosporins. At the time of diagnosis, candidemic patients were more likely to have required mechanical ventilation and were less likely to be tolerating enteral feeding. Multivariate clustered logistic regression analysis revealed that candidemic patients had more exposure to third-generation cephalosporins. Once the clinician was notified of a positive blood culture for Candida, patients infected with C parapsilosis retained their central catheters longer than patients infected with C albicans. CONCLUSIONS: In this retrospective review, we were able to identify aspects of the clinical presentation and medication history that may be helpful in differentiating between candidemia and CoNS bacteremia. Those key features may be used by clinicians to initiate empiric amphotericin B therapy in premature neonates at risk for nosocomial infections. Prolonged use of third-generation cephalosporins was strongly associated with candidemia. There was no statistically significant difference in the morbidity and mortality between patients infected with C parapsilosis and those infected with C albicans. Observed delays in removal of the central venous catheter may have contributed to finding a mortality rate from C parapsilosis that was higher than was previously reported.

Candidal mycetoma in the neonatal kidney.

OBJECTIVE: To determine the natural history of renal mycetoma (fungal balls) in the neonate. DESIGN: Retrospective chart review of all neonatal intensive care unit patients with systemic candidiasis and sonographic evidence of renal mycetoma admitted to the Duke University Medical Center between January 1, 1993, and July 1, 1998. RESULTS: Fourteen patients were reviewed. Three died from fungemia, and 3 died from other causes months after completing treatment. Ten patients had urine cultures obtained within 1 week of diagnosis; each had a positive routine or fungal urine culture for candida. The rate of improvement of renal mycetoma by ultrasound was variable, ranging from 10 days to 4 months and was not predictive of survival or long-term renal function. All patients who were discharged from the hospital had creatinine

Passive IgA monoclonal antibody is no more effective than IgG at protecting mice from mucosal challenge with respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a mucosally restricted pathogen that can cause severe respiratory disease. Although parenteral administration of sufficient RSV-specific IgG can reduce severity of lower respiratory tract infection in high-risk infants, delivery of antibody by direct airway administration is an attractive alternative. Topical and parenteral administration of an IgA monoclonal antibody (MAb) specific for the RSV F glycoprotein was compared with an IgG MAb, specific for the same antigenic site, for ability to protect mice against RSV infection. Administration of RSV-specific IgG was more effective in reducing RSV titers in lung (4.6 log10 pfu/g) than IgA MAb (3.6 log10 pfu/g) when given intranasally immediately prior to infection (P=.005). RSV titers in the nose were reduced only by prophylactic administration of IgG parenterally. Therefore, topical administration of IgA is no more effective than topically administered IgG and is less effective than systemically administered IgG for protecting against RSV infection.

Prophylaxis with respiratory syncytial virus F-specific humanized monoclonal antibody delays and moderately suppresses the native antibody response but does not impair immunity to late rechallenge.

Respiratory syncytial virus (RSV) is the most significant viral cause of lower respiratory tract disease in infants and children. This study tested the hypothesis that a humanized murine monoclonal antibody (MAb) would protect against RSV infection in mice and have minimal suppressive effect upon the immune response because it is directed against a single epitope. A humanized murine MAb (RSHZ19) was tested for both prophylaxis and treatment of RSV infection in BALB/c mice and compared with a polyclonal product. Mice were rechallenged when passively administered antibody was undetectable (day 104). RSHZ19 reduced virus titer and protected against illness when used in prophylaxis and effected rapid virus clearance when used as treatment. Polyclonal antibody was also an effective prophylaxis but required 200 times the dose in total protein. Peak neutralizing antibody responses were delayed and somewhat suppressed in the prophylactically treated groups, but mice were protected against infection on rechallenge. Secondary antibody response to rechallenge in passively immunized mice was equal to that in untreated mice.

Incidence and management of catheter occlusion in implantable arm ports: results in 391 patients.

PURPOSE: To evaluate the incidence and management of catheter occlusion in implantable arm ports. MATERIALS AND METHODS: Findings were prospectively examined in 391 patients in whom 393 arm ports were placed. The indications for port placement included chemotherapy (n = 347), antibiotic administration (n = 35), combination chemotherapy/antibiotic use (n = 7), transfusion (n = 3), and phlebotomy (n = 1). Of the total catheters, 323 (82.2%) underwent tip modification prior to placement. Malfunctioning catheters were usually treated with urokinase instillation. RESULTS: Three hundred ninety-three devices were implanted with 247 mean days of catheter use (total, 97,256 days; range, 1-694 days). The overall incidence of catheter occlusion was 0.14 per 100 catheter days. A single catheter occlusion occurred in 90 (22.9%) catheters, with a mean of 90.1 days before the event. A second occlusion occurred in 36 (9.2%) of the above catheters, with a mean of 60.1 catheter days before the second event. Eighty-five (24.0%) of the 347 cancer patients had at least one occlusive event, yielding a complication rate of 0.098 per 100 catheter days at risk (95% confidence interval [CI]; 0.079-0.114). Of the 35 patients receiving antibiotics, three (8.6%) had at least one occlusive event. This represented a complication rate of 0.032 per 100 catheter days at risk (95% CI; 0.010-0.061). Seventeen (24.3%) of the nonmodified catheters developed an occlusion versus 72 (22.3%) of the modified (P > .05; Fisher exact test). Of the catheters with a first occlusive event, 75 (98.7%) were treated successfully with urokinase instillation. Four (1.0%) patients developed symptomatic subclavian vein thrombosis. No bleeding complications occurred. CONCLUSION: Catheter occlusion is a common complication of long-term arm port placement, with a significantly higher incidence in the cancer patients in our series (P <. 05, Fisher exact test). Catheter tip modification, however, does not considerably affect the incidence of occlusion. Low-dose urokinase therapy is a safe and efficacious treatment of catheter occlusion, obviating the need for catheter removal.

Infectious complications of 393 peripherally implantable venous access devices in HIV-positive and HIV-negative patients.

PURPOSE: To compare and investigate the rate of infection in patients with and without human immunodeficiency virus (HIV) who have implantable venous access devices placed by interventional radiologists. MATERIALS AND METHODS: Three hundred ninety-one patients undergoing radiologically guided placement of peripheral arm ports were grouped according to their HIV serologic status. Findings were prospectively reviewed in 393 peripherally placed arm ports that were implanted in the basilic, cephalic, or brachial vein under fluoroscopic or sonographic guidance over a 4-year span. Infectious complications were categorized according to severity (local or systemic) and time (periprocedural or late). RESULTS: Three hundred ninety-three ports have been indwelling for a total of 97,256 patient days (range, 1-694; mean duration, 247 days). Among the 30 catheter placements in 29 HIV-positive patients with a total exposure time of 7,242 days, five (one local and four systemic) infections occurred, resulting in a 16.6% overall infection rate, yielding 0.069 infections per 100 catheter days at risk (95% confidence interval [CI], 0.032-0.127). In the remaining 362 HIV-negative patients, 27 (14 local and 13 systemic) infectious complications (7.4%) occurred, translating into 0.030 infections per 100 catheter days (95% CI, 0.021-0.042). The odds ratio of getting an infection from the implantable arm ports in the HIV-positive group was 2.5 times higher than that of the HIV-negative group. The relative risk was similar and was calculated to be 2.3. The P value was .084 (P < .05 required to be considered significant). CONCLUSIONS: These results suggest a significant difference in the infectious complication rate encountered in HIV-positive patients compared with the general population. However, the HIV-positive peripheral arm port infection rate compares favorably with the surgically placed catheters and ports. Many more arm ports in HIV-positive patients must be evaluated for the data to achieve an acceptable level of statistical significance.

Vascular gene therapy.

Gene therapy is an exciting frontier in medicine today. Radiologists will be involved in tracking the effects of these new therapies through imaging. Vascular and interventional radiology techniques also are ideally suited for minimally invasive, readily monitored gene delivery. Gene therapy is accomplished through gene augmentation or gene blocking. The latter is accomplished through antisense oligonucleotides or transcription factor decoys. Vectors are agents that facilitate gene delivery and expression and can be viral or nonviral. The vascular wall is an ideal target for gene therapy because of its central role in many biologic processes and its ready accessibility. Recombinant genes can be delivered ex vivo and in vivo, with the latter approaches involving open surgical, percutaneous injection, and endovascular catheter-based methods. Perforated, hydrogel-coated, and double balloon catheters have been used with varying success. Optimal catheter systems for gene transfer will enable delivery of the vector to the precise anatomic location with transfection limited to the cells of interest and will minimize shedding of the vector to distal sites, systemic effects of the therapeutic agent, and morbidity from the delivery method. Radiologists must become familiar with the basic rationale, strategies, and mechanisms of gene therapy and involved in its clinical trials to ensure an active role in this field.

"Lumps" and "bumps" that mimic acute aortic and brachiocephalic vessel injury.

Laceration of the thoracic aorta or brachiocephalic vessels due to blunt trauma is relatively common. In such cases, prompt and accurate diagnosis followed by timely surgery is essential. These injuries typically occur at the aortic isthmus and can usually be readily identified at aortography, which remains the standard of reference for diagnosis. However, numerous anatomic variants that manifest as "lumps" or "bumps" on aortograms can mimic true vascular injury, thereby leading to false-positive or false-negative diagnosis. These variants include aortic spindle, classic or atypical ductal diverticula, and infundibula of the brachiocephalic arteries and adjacent branches or of the right third intercostal artery. Ductus diverticula typically occur at the isthmus and have smooth, uninterrupted margins with gently sloping shoulders. Infundibula are also smoothly marginated but can occur in a variety of locations and generally taper into one or more vessels at their apex. Knowledge of the imaging appearances of these anatomic variants is necessary for correct interpretation of aortograms of the aorta and brachiocephalic vessels in blunt trauma patients.

Subtle or atypical injuries of the thoracic aorta and brachiocephalic vessels in blunt thoracic trauma.

Aortic or brachiocephalic vessel injuries secondary to blunt thoracic trauma are relatively common and can occur throughout the length of the thoracic aorta or in various locations in the brachiocephalic vessels. Aortography remains the standard of reference for the diagnosis of these injuries despite recent technologic advances in other imaging modalities. The classic aortographic finding in aortic or brachiocephalic vessel injury consists of a large false aneurysm, typically protruding from the medial aspect of the aortic isthmus. However, intrathoracic aortic or brachiocephalic vessel injury can and does occur at any intrathoracic location and may exhibit a wide variety of radiographic appearances, thereby presenting a diagnostic challenge even for experienced trauma angiographers. Large false aneurysms may appear oval or rounded, tubular, or asymmetrically globular and may manifest in unusual locations such as the ascending aorta. Although smaller, irregularly shaped false aneurysms at atypical locations may be obscure or mimic ductus diverticula, their irregular, sharp margins allow them to be distinguished as injuries. The subtlety of aortic or brachiocephalic vessel injuries necessitates a high degree of suspicion along with meticulous imaging technique in all cases and the use of additional projections in equivocal cases for definitive diagnosis.

Twenty years of outpatient respiratory syncytial virus infection: a framework for vaccine efficacy trials.

BACKGROUND: Respiratory syncytial virus (RSV) is the most important viral respiratory pathogen of infancy and childhood. Much has been written about inpatients with severe disease. Inpatients, however, represent only a minority of RSV-infected children. We studied the characteristics of symptomatic outpatient RSV infection in healthy children to gain a better understanding of RSV disease and to provide a background for the testing of intervention strategies in children without high-risk conditions. METHODS: A total of 1113 children were followed during 20 consecutive RSV seasons. Signs and symptoms of respiratory infection were monitored. Cultures were obtained for febrile upper respiratory infection, acute otitis media, and lower respiratory infection (LRI). Rates of febrile upper respiratory infection, acute otitis media, LRI, and hospitalization were calculated. Given those rates, numbers of children needed to demonstrate efficacy of a vaccine product were calculated. RESULTS: Mild disease from RSV infection lacked some of the classic features of RSV infection seen in hospitalized children. Involvement of the lower respiratory tract was, however, noted to be much higher in RSV infection than it was in infection with other viral respiratory pathogens. LRI was, therefore, considered the best candidate endpoint for vaccine trials. A product with 60% efficacy could be proven, with a power of 0.8, to be efficacious with as few as 1500 infants. CONCLUSIONS: RSV infection is common and often involves the lower respiratory tract, even in outpatients. Our 20-year study of RSV infection provides a basis for calculation of sample sizes to be used in trials of vaccine candidates.