Publications

Genomics and proteomics have emerged as key technologies in biomedical research, resulting in a surge of interest in training by investigators keen to incorporate these technologies into their research. At least two types of training can be envisioned in order to produce meaningful results, quality publications and successful grant applications: (1) immediate short-term training workshops and (2) long-term graduate education or visiting scientist programs. We aimed to fill the former need by providing a comprehensive hands-on training course in genomics, proteomics and informatics in a coherent, experimentally-based framework. This was accomplished through a National Heart, Lung, and Blood Institute (NHLBI)-sponsored 10-day Genomics and Proteomics Hands-on Workshop held at National Jewish Health (NJH) and the University of Colorado School of Medicine (UCD). The course content included comprehensive lectures and laboratories in mass spectrometry and genomics technologies, extensive hands-on experience with instrumentation and software, video demonstrations, optional workshops, online sessions, invited keynote speakers, and local and national guest faculty. Here we describe the detailed curriculum and present the results of short- and long-term evaluations from course attendees. Our educational program consistently received positive reviews from participants and had a substantial impact on grant writing and review, manuscript submissions and publications.

A 60-year-old man on chronic corticosteroids developed diplopia, gait instability and facial weakness. Brain MRI revealed a multiloculated pontine lesion. Cerebrospinal fluid (CSF) analysis demonstrated a neutrophil-predominant pleocytosis with elevated protein and low glucose. CSF cultures were negative, as was an extensive infectious diseases evaluation. Neurosurgical intervention was deferred in favour of empiric antimicrobial therapy due to the lesion's inaccessible location. After discontinuation of therapy, the patient reported a severe headache. A subsequent MRI demonstrated intraventricular pus. CSF culture grew Nocardia farcinica. The patient received parenteral therapy followed by oral trimethoprim-sulfamethoxazole. At 9 months, he is symptom free. This case illustrates the importance of including Nocardia in the differential diagnosis of brainstem abscesses, especially in immunocompromised patients. The availability of antimicrobial agents with excellent Nocardia activity and CSF penetration may enable treatment of brainstem abscesses for which surgical intervention has traditionally been considered necessary with medical management alone.

6-min walk distance (6MWD) has recently been shown to be associated with the risk of mortality in patients with idiopathic pulmonary fibrosis (IPF); however, the independent contribution of 6MWD to the prediction of mortality risk has not been evaluated in a large, well-defined population of patients with IPF. A Cox proportional hazards model was used to characterise the relationship between risk factors of interest and all-cause mortality in IPF patients who completed a week 24 study visit in a clinical trial evaluating interferon γ-1b (n=748). Risk factors of interest included the independent predictors of mortality in the previously published clinical prediction model together with 6MWD and 24-week change in 6MWD. Baseline 6MWD <250 m was associated with a two-fold increase in the risk of mortality (hazard ratio 2.12, 95% CI 1.15-3.92) and a 24-week decline in 6MWD >50 m was associated with a nearly three-fold increase in mortality risk (hazard ratio 2.73; 95% CI 1.60-4.66). Inclusion of 6MWD data improved model discrimination compared with the original model (C-statistic 0.80 (95% CI 0.76-0.85) versus 0.75 (0.71-0.79)). Both 6MWD and change in 6MWD are independent predictors of mortality in patients with IPF. The addition of 6MWD to the clinical prediction model improves model discrimination compared with the original model.

BACKGROUND

The purpose of the present study was to quantify perfusion to the femoral head and head-neck junction using gadolinium-enhanced magnetic resonance imaging following three surgical dislocations of the hip (trochanteric flip osteotomy, standard posterior approach, and modified posterior approach).

METHODS

The medial femoral circumflex artery was cannulated in fifty fresh-frozen cadaveric hips (twenty-five pelvic specimens). One hip on each pelvic specimen was randomly chosen to undergo one of the three surgical dislocations, and the contralateral hip was used as a control. Gadolinium enhancement on the magnetic resonance imaging scan was quantified in both the femoral head and head-neck junction by volumetric analysis using custom magnetic resonance imaging analysis software. A polyurethane compound was then injected, and gross dissection was performed to assess the extraosseous vasculature.

RESULTS

Magnetic resonance imaging quantification revealed that the trochanteric flip osteotomy group maintained almost full perfusion (mean, 96% for the femoral head and 98% for the head-neck junction). The standard posterior approach almost completely compromised perfusion (mean, 4% for the femoral head and 8% for the head-neck junction). Six specimens in the modified posterior approach group demonstrated partial perfusion (mean, 32% in the femoral head and 26% in the head-neck junction). Three specimens in the modified posterior approach group demonstrated almost full perfusion (mean, 96% in the femoral head and 97% in the head-neck junction). Gross dissection revealed that all specimens in the standard posterior approach group and seven of ten in the modified posterior approach group sustained disruption of the ascending branch of the medial femoral circumflex artery. All specimens in the standard posterior approach group demonstrated disruption of the inferior retinacular artery. The inferior retinacular artery remained intact in nine of ten specimens in the modified posterior approach group. One specimen in the modified posterior approach group that had disruption of both the ascending medial femoral circumflex artery and inferior retinacular artery demonstrated a substantial decrease in perfusion (7% in the femoral head and 5% in the head-neck junction).

CONCLUSIONS

The trochanteric flip osteotomy preserves the vascular supply to the femoral head and head-neck junction. The standard posterior approach disrupts the vascular supply and should be completely abandoned for surgical hip dislocation. Despite reduced enhancement, substantial perfusion of the femoral head and head-neck junction was present in the modified posterior approach group, likely because of the preservation of the inferior retinacular artery. The modified posterior approach produced variable results, indicating that improvement to the modified posterior approach is needed.

CLINICAL RELEVANCE

Our study provides previously unreported quantitative magnetic resonance imaging data on the perfusion to the femoral head and head-neck junction during common surgical approaches to the hip.