Prognostic implications of genetic aberrations in acute myelogenous leukemia with normal cytogenetics

Acute myelogenous leukemia (AML) is a genetically heterogeneous disease in which somatic mutations, that disturb cellular growth, proliferation, and differentiation, accumulate in hematopoietic progenitor cells. Cytogenetic findings, at diagnosis, have been proven to be one of the most important prognostic indicators in AML. About half of the patients with AML are found to have "normal" cytogenetic analysis by standard culture techniques. These patients are considered as an intermediate risk group. Cytogenetically normal AML (CN-AML) is the largest cytogenetic risk group, and the variation in clinical outcome of patients in this group is greater than in any other cytogenetic group. Besides mutation testing, age and presenting white blood cell count are important predictors of overall survival, suggesting that other factors independent of cytogenetic abnormalities, contribute to the outcome of patients with AML. The expanding knowledge at the genetic and molecular levels is helping define several subgroups of patients with CN-AML with variable prognosis. In this review, we describe the clinical and prognostic characteristics of CN-AML patients as a group, as well as the various molecular and genetic aberrations detected in these patients and their clinical and prognostic implications.     

Using virtual reality to explore the role of conflict resolution and environmental salience in Freezing of Gait in Parkinson's disease

BackgroundThe freezing phenomenon is among the most disabling symptoms of Parkinson's disease (PD) manifesting most commonly as Freezing of Gait with a paroxysmal cessation of effective stepping. Recent studies have suggested that freezing is related to both impairments in conflict resolution as well as the processing of environmentally salient information.MethodsIn this study, we utilized a virtual reality gait paradigm to investigate differences in motor outflow between PD patients with (n = 36) and without (n = 37) Freezing of Gait, as well as age-matched healthy controls (n = 18). Subjects were required to navigate a realistic on-screen environment with the use of foot pedals to simulate stepping whilst responding to either cues associated with conflict resolution (congruent ‘Red’, ‘Green’ or ‘Blue’) or environmental salience (wide, narrow and sliding doorways). Footstep latency was used as a measure of motor output.ResultsSignificantly increased stepping latencies were observed in freezers compared to non-freezers (p = 0.004) and controls (p = 0.016) in response to stimuli requiring the inhibition of implicitly cued behavior (‘red’ cue). Patients with Freezing of Gait also demonstrated increased motor latency compared to non-freezers and controls specifically in response to environmentally salient triggers including narrow doorways (p = 0.03 and 0.01 respectively) and the opening of a sliding door (p = 0.036 and 0.048 respectively). Performance on the paradigm in relation to these triggers correlated significantly with self-reported freezing severity.ConclusionThese results suggest that deficits in conflict resolution and visuospatial processing may reflect some of the neural mechanisms associated with freezing behavior and that these can be probed in a virtual reality environment.     

Blood flow to the heart from noncoronary arteries: an intriguing but challenging research field

IntroductionIt has been proven that blood supply to the heart can include blood from noncoronary collateral circulation. Whether this network can somehow be augmented to provide an alternative therapy for ischemic patients is an intriguing hypothesis with no clear answer yet due to the challenging nature of this research field. In an attempt to enhance noncoronary collateral blood flow, we experimented with left internal thoracic artery ligature and angiogenic growth factors in a canine model.Materials and methodsEight dogs weighing between 20 and 29 kg were scheduled for three operations each. Neutron-activated microspheres were used for blood flow measurement throughout the study. The first operation was a left thoracotomy for ameroid constrictor positioning at the proximal segment of the circumflex coronary artery. Three weeks later the left internal thoracic artery was ligatured distally. A micro-pump was positioned in the mediastinum, connected with a small catheter inserted in the proximal segment of the left internal thoracic artery for slow delivery of vascular endothelial growth factor. The protocol called for a coronary angiography 4 weeks later, sacrifice of the animals, and explantation of the heart for microsphere analysis.ResultsFour of the dogs failed to tolerate ameroid constrictor positioning by thoracotomy and died after the first operation. The remaining four dogs underwent a second operation to ligate their left internal thoracic arteries and implant micro-pumps with catheters. The implant was a success, but only one dog survived in the postoperative period. When the last dog was voluntarily sacrificed after a third operation, coronary angiography showed no neovascularization, nor did heart slice analysis reveal microspheres.ConclusionsDespite the technical challenge of building research protocols to exactly quantify blood from noncoronary arteries, there are many historical, anatomical, physiopathological, clinical, radiological, and surgical indications suggesting that blood flow from extracardiac structures may play an important role in ischemic heart disease. Our preliminary investigation combining internal thoracic artery occlusion and angiogenic growth factors was unsuccessful for several reasons, the main one being it was too heavy a protocol for the dogs. Despite this, we think that noncoronary collateral blood flow represents an intriguing research field worthy of debate and further study.     

Leukocyte Esterase From Synovial Fluid Aspirate : A Technical Note

Accurate and efficient diagnosis of periprosthetic joint infection remains one of the most challenging tasks for orthopedic surgeons. Currently, no widely used diagnostic test allows for quick and efficient performance, low cost, and high sensitivity and specificity. Aspiration of synovial fluid from a patient's joint can be done in the clinic both quickly and easily; oftentimes, the aspirate obtained is bloody, thus rendering the use of colorimetric strip testing impractical. We describe a simple, inexpensive, and effective protocol using centrifugation to allow for leukocyte esterase (LE) testing after bloody joint aspirations. In all cases, both septic and aseptic, there was a 100% concordance in LE enzyme test results. Although further validation may be necessary, these initial results demonstrate that accuracy of LE testing is not affected by centrifugation.     

Reoperative Surgery After Repair of Postcholecystectomy Bile Duct Injuries: Is it Worthwhile?

Background

Repeat repair of bile duct injuries (BDIs) after cholecystectomy is technically challenging, and its success remains uncertain. We retrospectively evaluated the short- and long-term outcomes of patients requiring reoperative surgery for BDI at a major referral center for hepatobiliary surgery.

Methods

Between January 1991 and May 2011, we performed surgical BDI repairs in 46 patients. Among them, 22 patients had undergone a previous surgical repair elsewhere (group 1), and 24 patients had no previous repair (group 2). We compared the early and late outcomes in the two groups.

Results

The patients in group 1 were younger (48.6 vs. 54.8 years, p = 0.0001) and were referred after a longer interval (>1 month) from BDI (72.7 vs. 41.7 %, p = 0.042). Intraoperative diagnosis of BDI (59.1 vs. 12.5 %, p = 0.001), ongoing cholangitis (45.4 vs. 12.5 %; p = 0.02), and delay of repair after referral to our institution (116 ± 34 days vs. 23 ± 9 days; p = 0.001) were significantly more frequent in group 1 than in group 2. No significant differences were found for postoperative mortality, morbidity, or length of stay between the groups. Patients with associated vascular injuries had a higher postoperative morbidity rate (p = 0.01) and associated hepatectomy rate (p = 0.045). After a mean follow-up of 96.6 ± 9.7 months (range 5–237.2 months, median 96 months), the rate of recurrent cholangitis (6.5 %) was comparable in the two groups.

Conclusions

This study demonstrates that short- and long-term outcomes after surgical repair of BDI are comparable regardless of whether the patient requires reoperative surgery for a failed primary repair. Associated vascular injuries increase postoperative morbidity and the need for liver resection.