Adipose tissue imaging as nutritional predictors in patients undergoing enterocutaneous fistula repair.

OBJECTIVES: The management of enterocutaneous fistulae (ECF) is complex, challenging, and often associated with metabolic, septic, and nutritional complications. Radiographic quantification of body composition such as fat or lean body mass distribution is a potentially valuable preoperative assessment tool to optimize nutritional status. The aim of this study was to investigate the correlation between total adipose tissue (fat) area (TFA), assessed by computed tomography and magnetic resonance imaging radiology tests, with body weight, body mass index (BMI), various biochemical parameters, need for nutritional support, and survival in patients undergoing ECF repair. METHODS: Biochemical and anthropometric parameters at the time of ECF surgery were retrospectively collected for adult patients undergoing ECF repair at University College London Hospital, UK. Visceral and subcutaneous adiposity was measured at the level of the third lumbar vertebra (Image J) at computed tomography or magnetic resonance imaging. Statistical analysis included descriptives, univariate and multivariate analysis between TFA and various parameters, and their influence on postoperative survival. RESULTS: A complete set of data was available for 85 patients (51 women, 56.9 ± 14.5 y of age) who underwent ECF repair. ECF originated mainly as a surgical complication (86%) while 14% were undergoing a second ECF repair. Median BMI was 22.8 kg/m2 and mean TFA was 361 ± 174.9 cm2, with a higher visceral fat content in men than in women (183.8 ± 99.2 versus 99 ± 59.7 cm2, P < 0.001). BMI, body weight, and creatinine were significantly positively correlated with TFA (ρ = 0.77, 0.73, and 0.50, respectively, P < 0.001); no correlation was noted between TFA and preoperative albumin levels. Patients in the low TFA group had a higher use of parenteral nutrition (P = 0.049). Hospital length of stay was longer in patients receiving artificial nutrition support (70 versus 22 d, P < 0.001). A TFA cutoff point of 290 cm2 discriminated patients who required artificial nutrition versus no nutritional support with moderate sensitivity (75%) but poor specificity (45%). At multivariate analysis, only >60 y of age (hazard ratio [HR], 2.69, P < 0.02) and use of parenteral nutrition (HR, 3.90, P < 0.02) were associated with worse overall survival. CONCLUSION: Abdominal adiposity was strongly correlated with anthropometric parameters at the time of surgery. Earlier identification of patients requiring artificial nutrition at standard preoperative imaging might allow integration of nutritional optimization into initial clinical management plans reducing length of stay and improving clinical outcomes.

Safety and immunogenicity study of Multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa.

BACKGROUND: We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults. METHODOLOGY/PRINCIPAL FINDINGS: Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×10(10) or 1×10(11) particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone. CONCLUSIONS/SIGNIFICANCE: The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints. TRIAL REGISTRATION: ClinicalTrials.gov NCT00124007.

Baseline morbidity in 2,990 adult African volunteers recruited to characterize laboratory reference intervals for future HIV vaccine clinical trials.

BACKGROUND: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. METHODS: Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). RESULTS AND CONCLUSIONS: Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons.

A prospective longitudinal study of cosmetic outcome in immediate latissimus dorsi breast reconstruction and the influence of radiotherapy.

BACKGROUND: Immediate breast reconstruction may result in superior cosmetic outcomes as a result of the preservation of the skin envelope. The impact of implant use and radiotherapy (RT) on the cosmetic outcome of latissimus dorsi (LD) breast reconstruction, however, has never been prospectively evaluated with adequate long-term follow-up. METHODS: Women undergoing immediate LD breast reconstruction from January 2000 to February 2007 underwent photographic assessment and clinical evaluation for breast retraction analysis (BRA) at 3, 6 and 12 months postoperatively and on the anniversary of their surgery. The resulting photographs were subject to panel cosmetic assessment. A patient-reported cosmetic outcome questionnaire and the body image scale (BIS) were administered to each woman at a single time point to coincide with the anniversary of their surgery. Multilevel linear regression modelling was used to analyse the results. RESULTS: Seventy-three women underwent 53 implant-assisted LD breast reconstructions and 20 autologous procedures with a mean follow-up of 2.71 years. The incidence of radiotherapy in this cohort was 43%. RT over time adversely influenced overall cosmetic outcome as assessed by the panel (P = 0.0002), and BRA (P = 0.033), both of which were significantly worse in the implant-assisted group (P = 0.020). Patient reporting of overall cosmetic outcome and BIS, however, did not differ significantly between the LD groups or following RT. CONCLUSION: Radiotherapy may adversely affect the cosmetic outcome of latissimus dorsi breast reconstruction, particularly if an implant is used, but this is not universal. Patient assessment of their cosmetic outcome may, however, differ significantly from the clinician's view.

Medical and surgical outcome of tricuspid regurgitation caused by flail leaflets.

OBJECTIVE: We sought to evaluate the medical and surgical outcome of tricuspid regurgitation caused by flail leaflets. METHODS: We analyzed the cause, clinical presentation, outcome, and natural history of 60 patients with tricuspid regurgitation caused by flail leaflets, a cause of mostly severe and organic tricuspid regurgitation, diagnosed by means of echocardiography between 1980 and 2000. RESULTS: The main cause was traumatic (62%). Clinical presentation was often severe: 57% were symptomatic, 33% had a history of congestive heart failure, and 40% had a history of atrial fibrillation. Compared with expected survival of the US matched population, excess mortality (39% +/- 10% at 10 years or 4.5% yearly, P <.01) was observed. Even patients asymptomatic at presentation experienced high tricuspid-related event rates (at 10 years, 75% +/- 15% had symptoms or heart failure, atrial fibrillation, surgical intervention, or death). In those patients severe enlargement of right-sided chambers was predictive of poor outcome (at 5 years: 86% +/- 9% vs 39% +/- 11%, P <.01) independent of cause (P =.31). The poor medical outcome was further confirmed by high event rates (69% +/- 9% at 15 years) in the natural history beginning from the flail's occurrence. Tricuspid operations were performed in 33 patients (55% +/- 7% at 5 years), with valve repair in 82%, low mortality (3%), and, despite frequently refractory atrial fibrillation, symptomatic improvement in 88%. CONCLUSION: Tricuspid regurgitation caused by flail leaflets is a serious disease associated with excess mortality and high morbidity. Tricuspid valve repair can often be performed with low risk, allowing symptomatic improvement. These results suggest that surgical intervention should be considered early in the course of the disease before the occurrence of irreversible consequences.