Close proximity to blast: No long-term or lasting effect on cognitive performance in service members with and without TBI during blast exposure.

OBJECTIVE: Blast related characteristics may contribute to the diversity of findings on whether mild traumatic brain injury sustained during war zone deployment has lasting cognitive effects. This study aims to evaluate whether a history of blast exposure at close proximity, defined as exposure within 30 feet, has long-term or lasting influences on cognitive outcomes among current and former military personnel. METHOD: One hundred participants were assigned to one of three groups based on a self-report history of blast exposure during combat deployments: 47 close blast, 14 non-close blast, and 39 comparison participants without blast exposure. Working memory, processing speed, verbal learning/memory, and cognitive flexibility were evaluated using standard neuropsychological tests. In addition, assessment of combat exposure and current post-concussive, posttraumatic stress, and depressive symptoms, and headache was performed via self-report measures. Variables that differed between groups were controlled as covariates. RESULTS: No group differences survived Bonferroni correction for family-wise error rate; the close blast group did not differ from non-close blast and comparison groups on measures of working memory, processing speed, verbal learning/memory, or cognitive flexibility. Controlling for covariates did not alter these results. CONCLUSION: No evidence emerged to suggest that a history of close blast exposure was associated with decreased cognitive performance when comparisons were made with the other groups. Limited characterization of blast contexts experienced, self-report of blast distance, and heterogeneity of injury severity within the groups are the main limitations of this study.

Validity of the CES-D for depression screening in military service members with a history of mild traumatic brain injury.

Primary Objective: To advance knowledge about the value of the Center for Epidemiologic Studies - Depression scale (CES-D) for depression screening in military service members with a history of mild traumatic brain injury (mTBI). Research Design: Retrospective data from 336 military service members with a history of mTBI were extracted from a TBI Repository at a large military medical center. Participants included in this study screened positive for mTBI in a primary care clinic or soldier readiness processing center and were enrolled in the TBI repository from November 6, 2014 to May 31, 2017. At the time of enrollment, participants completed the CES-D and their electronic medical records (EMR) were searched for diagnoses of depressive disorders. Methods and Procedures: Receiver-operating characteristic (ROC) analysis of the CES-D was used to discriminate cases with and without depression diagnoses. Main Outcomes and Results: Area under the ROC curve (AUC) was .897. Sensitivity (.824) and specificity (.826) were maximized at a cut score of 18 or greater, slightly higher than the standard cut of 16 established for civilian samples. Conclusions: Results suggest that the CES-D is a valid screening instrument for depressive disorders in military samples with a history of mTBI.

Preliminary findings of cortical thickness abnormalities in blast injured service members and their relationship to clinical findings.

Though cortical abnormalities have been demonstrated in moderate and severe traumatic brain injured (TBI) patients, there have been no studies examining cortical changes following blast related mild TBI (mTBI). The purpose of this study was to determine the effects and functional relevance of blast mTBI on cortical thickness in a small cohort of carefully screened blast injured US Service Members (SM). Twelve SM with mTBI acquired through blast injury were compared to 11 demographically matched control SM without TBI. Both mTBI and control participants were active duty and had completed a combat deployment. Subjects underwent MRI examination and the T1 weighted anatomic images were processed using the FreeSurfer suite of tools. Cortical thickness maps were compared between groups and examined for relationships with time since injury (TSI). Utilizing a large database of functional imaging results (BrainMap), significant regions of interest (ROI) were used to determine the behavioral profiles most consistently associated with the specific ROI. In addition, clinical variables were examined as part of post-hoc analysis of functional relevance. Group comparisons controlling for age demonstrated several significant clusters of cortical thinning for the blast injured SM. After multiple comparisons correction (False Discovery Rate (FDR)), two left hemisphere clusters remained significant (left superior temporal (STG) and frontal (SFG) gyri). No clusters were significantly correlated with TSI after FDR correction. Behavioral analysis for the STG and SFG clusters demonstrated three significant behavioral/cognitive sub-domains, each associated with audition and language. Blast injured SMs demonstrated distinct areas of cortical thinning in the STG and SFG. These areas have been previously shown to be associated with audition and language. Post-hoc analyses of clinical records demonstrated significant abnormal audiology reports for the blast injured SM suggesting that the thinning in these ROIs might be related to injury to the external auditory system rather than direct injury to the brain from the blast. It is clear that additional replication is needed in much larger cohorts. Importantly, the combination of imaging tools and methods in this study successfully demonstrated the potential to define unique ROIs and functional correlates that can be used to design future studies.

Complicated lymphogranuloma venereum infection mimicking deep vein thrombosis in an HIV-positive man.

A 41-year-old HIV-positive man who has sex with men (MSM) with a family history of deep vein thrombosis (DVT) presented to the emergency department with an acutely swollen lower limb. The initial clinical diagnosis was of a possible DVT and the patient was anticoagulated. However, investigations subsequently excluded DVT and sexually acquired reactive arthropathy (SARA) was eventually diagnosed. This complication followed an earlier attendance at the emergency department, where proctitis due to lymphogranuloma venereum (LGV) infection went unrecognized. This is the first reported case of LGV infection mimicking a DVT. Prompt recognition and treatment of the initial proctitis may have prevented the development of SARA.

The use of time to maximum enhancement to indicate areas of ablation following the treatment of liver tumours with high-intensity focused ultrasound.

The aim of this study was to investigate the use of time to maximum enhancement (t(max)) for each voxel in contrast-enhanced MRI (CE-MRI) as a non-invasive tool to determine areas of necrosis following treatment of liver tumours with high-intensity focused ultrasound (HIFU) and, having established the utility of t(max) maps, to develop a three-dimensional (3-D) representation to display this information concisely. 3-D T(1) weighted fast spoiled gradient echo images of the liver were acquired before and after administration of contrast agent. The CE-MR images were aligned to the pre-contrast volume and an estimate of t(max) was obtained for each voxel. Such pre- and post-contrast image sets were acquired before and after ablation. The t(max) maps before and after HIFU treatment were correlated with the procedure notes, radiological reports and gross histological specimen. Finally, 3-D t(max) maps of the whole liver were reconstructed to show all areas of abnormal tissue perfusion. Normal, healthy liver tissue uniformly enhances maximally after approximately 1 min. The computed t(max) maps accurately delineated areas of abnormal contrast agent uptake, corresponding to tumour deposits. Changes in t(max) and non-enhancing voxels after treatment correlate well with volumes targeted during ablation and the necrotic regions seen on gross histological specimens. Alignment of the contrast-enhanced images with the pre-contrast volume greatly improved the conspicuity of the t(max) maps. We conclude that t(max) maps and their 3-D views can be used as a non-invasive tool to assess and potentially to quantify the success of HIFU ablation, and concisely represent the large number of CE-MRI data.

High-intensity focused ultrasound ablation of liver tumours: can radiological assessment predict the histological response?

Cancer therapies usually depend on cross-sectional imaging for the assessment of treatment response. This study was designed to evaluate the ability of MRI to predict zones of necrosis following the use of high-intensity focused ultrasound (HIFU) to treat liver metastases. Patients with liver metastases, who had been scheduled for elective surgical resection of their tumours, were recruited to this non-randomized Phase II study. In each case, a proportion of an index liver tumour target was ablated. The response to HIFU was assessed after 12 days using contrast-enhanced MRI and compared directly with histological analysis at the time of surgery. Eight patients were treated, of whom six were subsequently assessed with both MRI and histology. There were no major complications. MRI predicted complete ablation in three cases. In each case, histological analysis confirmed complete ablation. In one case, the region of ablation observed on MRI appeared smaller than predicted at the time of HIFU, but histology revealed complete ablation of the target region. The predominant characteristic of HIFU-ablated tissue was coagulative necrosis but heat fixation was evident in some areas. Heat-fixed cells appeared normal under haematoxylin and eosin staining, indicating that this is unreliable as an indicator of HIFU-induced cell death. This study demonstrates that HIFU is capable of achieving selective ablation of pre-defined regions of liver tumour targets, and that MRI evidence of complete ablation of the target region can be taken to infer histological success.

Differential expression of CXCL12 and CXCR4 during human fetal neural progenitor cell differentiation.

Stromal cell-derived factor 1 alpha (SDF-1alpha, CXCL12) and its receptor CXCR4 play an important role in the central nervous system (CNS) development and adulthood by mediating cell migration, enhancing precursor cell proliferation, assisting in neuronal circuit formation, and possibly regulating migration during repair. The expression pattern of CXCR4 and CXCL12 during neurogenesis has not been thoroughly elucidated. In this study, we investigated the expression of CXCL12 and CXCR4 during neural progenitor cells (NPC) differentiation by microarray analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) using human fetal NPC as a model system. The production of CXCL12 was measured by enzyme-linked immunosorbent assay (ELISA). CXCR4 expression was determined by florescence-activated cell sorting (FACS) analysis, immunocytochemical staining, and CXCR4-mediated inhibition of cyclic AMP (cAMP) accumulation. Our data demonstrated that CXCR4 expression is significantly upregulated when NPC are differentiated into neuronal precursors, whereas CXCL12 is upregulated when differentiated into astrocytes. We also provide evidence that CXCR4 localization changes as neurons mature. In neuronal precursors, CXCR4 is localized in both neuronal processes and the cell body, whereas in mature neurons, it is primarily expressed on axons and dendrites. This differential expression of CXCR4 and CXCL12 may be important for the temporal regulation of neuronal migration and circuit formation during development and possibly in adult neurogenesis and repair.

High intensity focused ultrasound in the treatment of abdominal and gynaecological diseases.

In recent years high intensity focused ultrasound (HIFU) has received increasing interest as a non-invasive modality for the treatment of tumours of solid organs. Surgeons continue their quest to find the optimal technique whereby a diseased organ can be treated with a minimum of damage to the patient, while providing a comprehensive treatment to produce either cure or resolution of symptoms. Two of the areas in which HIFU is beginning to establish itself as a real therapeutic alternative, are in the treatment of abdominal and gynaecological disease. In this paper, we will review the literature available regarding the use of HIFU in the treatment of various organs: liver, kidney, pancreas, bladder, uterus and vulva.

The safety and feasibility of extracorporeal high-intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population.

High-intensity focused ultrasound (HIFU) provides a potential noninvasive alternative to conventional therapies. We report our preliminary experience from clinical trials designed to evaluate the safety and feasibility of a novel, extracorporeal HIFU device for the treatment of liver and kidney tumours in a Western population. The extracorporeal, ultrasound-guided Model-JC Tumor Therapy System (HAIFU Technology Company, China) has been used to treat 30 patients according to four trial protocols. Patients with hepatic or renal tumours underwent a single therapeutic HIFU session under general anaesthesia. Magnetic resonance imaging 12 days after treatment provided assessment of response. The patients were subdivided into those followed up with further imaging alone or those undergoing surgical resection of their tumours, which enabled both radiological and histological assessment. HIFU exposure resulted in discrete zones of ablation in 25 of 27 evaluable patients (93%). Ablation of liver tumours was achieved more consistently than for kidney tumours (100 vs 67%, assessed radiologically). The adverse event profile was favourable when compared to more invasive techniques. HIFU treatment of liver and kidney tumours in a Western population is both safe and feasible. These findings have significant implications for future noninvasive image-guided tumour ablation.

High-intensity focused ultrasound for the treatment of liver tumours.

High-intensity focused ultrasound (HIFU) has been investigated as a tool for the treatment of cancer for many decades, but is only now beginning to emerge as a potential alternative to conventional therapies. In recent years, clinical trials have evaluated the clinical efficacy of a number of devices worldwide. In Oxford, UK, we have been using the JC HIFU system (HAIFU Technology Company, Chongqing, PR China) in clinical trials since November 2002. This is the first report of its clinical use outside mainland China. The device is non-invasive, and employs an extracorporeal transducer operating at 0.8-1.6 MHz (aperture 12-15 cm, focal length 9-15 cm), operating clinically at Isp (free field) of 5-15 KWcm(-2). The aims of the trials are to evaluate the safety and performance of the device. Performance is being evaluated through two parallel protocols. One employs radiological assessment of response with the use of follow-up magnetic resonance imaging and microbubble-contrast ultrasound. In the other, histological assessment will be made following elective surgical resection of the HIFU treated tumours. Eleven patients with liver tumours have been treated with HIFU to date. Adverse events include transient pain and minor skin burns. Observed response from the various assessment modalities is discussed.

A study of blood cross-matching requirements for surgery in gynecological oncology: improved efficiency and cost saving.

The objective of this study was to design and implement a maximum surgical blood order schedule (MSBOS) within a specialist gynecological oncology department in a tertiary referral center and evaluate its impact on the cross-match to transfusion ratio (CTR). A retrospective case note audit was undertaken to identify common operations performed within the unit and their transfusion requirements. The efficiency of blood usage was assessed using the CTR, and an MSBOS was devised and implemented. A prospective audit of preoperative blood cross-matching and subsequent blood usage was then performed for consecutive elective operations in the unit, to assess the effect of the MSBOS. The retrospective study of 222 cases demonstrated a CTR of 2.25 equivalent to 44% usage of cross-matched blood. Ninety two percent of operations performed within the unit could be incorporated into an MSBOS. The prospective study of 207 cases demonstrated a significantly reduced CTR of 1.71 or 59% blood usage (chi2 = 12.4, P < 0.001). This equates to a saving of 102 units of blood over the 15 months prospective audit. Protocol adherence was 77%. No patient was adversely affected by the adoption of the MSBOS. We conclude that an MSBOS can be safely introduced into a gynecological oncology department resulting in significant financial savings.

High intensity focused ultrasound: surgery of the future?

For 50 years, high intensity focused ultrasound (HIFU) has been a subject of interest for medical research. HIFU causes selective tissue necrosis in a very well defined volume, at a variable distance from the transducer, through heating or cavitation. Over the past decade, the use of HIFU has been investigated in many clinical settings. This literature review aims to summarize recent advances made in the field. A Medline-based literature search (1965-2002) was conducted using the keywords "HIFU" and "high intensity focused ultrasound". Additional literature was obtained from original papers and published meeting abstracts. The most abundant clinical trial data comes from studies investigating its use in the treatment of prostatic disease, although early research looked at applications in neurosurgery. More recently horizons have been broadened, and the potential of HIFU as a non-invasive surgical tool has been demonstrated in many settings including the treatment of tumours of the liver, kidney, breast, bone, uterus and pancreas, as well as conduction defects in the heart, for surgical haemostasis, and the relief of chronic pain of malignant origin. Further clinical evaluation will follow, but recent technological development suggests that HIFU is likely to play a significant role in future surgical practice.

Building on our accomplishments.

BACKGROUND AND OVERVIEW: There are at least five forces--knowledge, finances, diversity, faculty and government--that have the potential to change the current model of dental education significantly in the new century. The author explores these forces and attempts to project their future impact on dental education and the profession. CONCLUSIONS: Our understanding of the etiology and pathogenesis of oral diseases will increase, though likely not enough to facilitate the elimination of either dental caries or adult-onset periodontitis. A mandatory year of additional formal education in the form of a postgraduate residency will become necessary. Current trends in the sources of revenue supporting dental education will continue, and dental education will face a financial crisis. The changing ethnic and racial diversity of the United States and the dental work force will require curricular changes to prepare students to meet the oral health needs of diverse populations. The current shortage of full-time dental faculty members will continue, and dental schools will need to redefine what it means to be a faculty member. Finally, the continuing decline in the dentist:population ratio and a peak in the actual number of active dentists will cause government to again question the adequacy of the dental work force. PRACTICE IMPLICATIONS: Academic dentistry faces a new century with new challenges, all of which have implications for current and future dental practitioners. The extent to which these challenges are successfully met will depend on the degree to which those with a vested interest in a thriving profession come together for the mutual benefit of all.

Exposures to blood and body fluids among dental school-based dental health care workers.

A survey of United States dental schools was conducted to determine the annual incidence of reported percutaneous and mucosal exposures to blood and other body fluids among dental school-based dental health care workers (DHCW). A response rate of 51.9 percent provided information on 10,433 DHCW and 1.6 million student clinic and 169,836 school-based faculty practice patient visits. This response represents approximately half of all DHCW and student clinic visits in U.S. dental schools in AY 1996/1997. A total of 652 exposures were reported, of which 629 occurred in student clinics. Dental schools averaged twenty-three reported exposures per year, and the overall annual reported exposure rate in student clinics was 4.0/10,000 patient visits and 1.3/10,000 in faculty practice. Dental students accounted for 62.5 percent of all reported exposures, a rate of 106.3/1000 students per year. The exposure rate for dental students was significantly greater that any other category of DHCW. Expressed in terms of person years, an exposure rate of 0.17 was comparable to that reported for dental schools but considerably less than found in other dental care settings. A second survey directed to individual DHCW drew responses from only 8.3 percent of the 10,433 DHCW. Among these respondents, 31 percent of those acknowledging an exposure reported it. A judgment that the injury was not serious, the time necessary to report an exposure, and a belief that the patient was healthy were the primary reasons for not reporting. The results of this study provide dental schools with benchmarks for comparing their reported exposure experience and assessing programs intended to prevent and manage exposures.