Geriatric trauma: resource use and patient outcomes.

INTRODUCTION: Elderly patients who suffer trauma have a higher mortality and use disproportionately more trauma resources than younger patients. To compare these 2 groups and determine the outcomes and characteristics of elderly patients, we reviewed patients in these 2 groups admitted and treated in our tertiary care provincial trauma centre. METHODS: From the provincial trauma registry we selected a cohort of 40 geriatric patients (group 1) (> or = 65 yr of age) with an ISS of 16 or more who were admitted to and spent time in our trauma service for more than 48 hours and compared them with a similar randomly selected cohort of 44 patients (group 2) aged 20-30 years. Family physicians were contacted for follow-up of these patients 2 years after discharge. We considered length of hospital stay, complications, disposition of the patients and use of consultation services. RESULTS: Patients in group 1 had a mean age of 72.1 years (range from 65-98 yr) and a mean ISS of 27.3 (range from 17-50). Patients in group 2 had a mean age of 26.3 years (range from 22-29 yr) and a mean ISS of 26.3 (range from 17-54). Hospital stay was significantly longer in the group 1: 34.5 days (95% confidence interval [CI]: 24-44 d) versus 21.6 days (95% CI: 15-28 d). More elderly patients experienced complications (35 v. 13, p < 0.001) and required medical consultations (35 v. 26, p < 0.001). In-hospital death rates were 8% (3 of 40) and 4% (2 of 44) respectively (p = 0.3). Fewer geriatric patients could be discharged home (35% [14 of 40] v. 27% [22 of 44], p = 0.056) or to rehabilitation facilities (28% [11 of 40] v. 34% [15 of 44], p = 0.3). Five geriatric patients were discharged to nursing homes (p = 0.007). Of the geriatric patients discharged to rehabilitation facilities or home, 75% were independent 2 years after discharge. CONCLUSIONS: Aggressive care for geriatric trauma patients is warranted, and resources should be directed toward rehabilitation. Based on our findings, we expect that creating a directed care pathway for these patients, targetting complications and earlier discharge, will further improve their outcomes.     

Application of stem cells in bone repair

Bone has the ability to repair minor injuries through remodeling. However, when the host source of osteoprogenitors is compromised at the defect site, one effective treatment may be cell-based therapy, as it replenishes the area of bone loss with cells possessing osteogenic potential. This review is a concise comparison of different types of stem cells that have the potential to be used in tissue-engineered scaffolds for bone repair. The clinical use of mesenchymal stem or stromal cells isolated from the bone marrow for treating various diseases has been well documented. However, the scarcity of these cells prompts the search for alternative sources of multipotential cells such as amniotic fluid stem cells and umbilical cord perivascular cells. Embryonic stem cells are another controversial source of cells with osteogenic potential. These cells have the ability to differentiate into all cell types of the adult body. Issues such as the use of human embryos and the risk of contamination from animal-derived culture components continue to prevent the therapeutic use of ESCs. As a result, abundant research has been carried out to design defined culture conditions for culturing ESCs, and alternative strategies such as the generation of induced pluripotent stem cells are being developed to eliminate the need for using embryos for cell derivation. In addition to the cell source, the ability to control stem cell differentiation into functional bone and the choice of biomaterial are also paramount objectives that are being examined in research and clinical trials.     

Lymphatic mapping with 99mTc-Evans Blue dye in sheep

Objective   ^99mTc-Evans Blue (EB) is an agent that contains both radioactive and color signals in a single dose. Earlier studies in animal models have suggested that this agent when compared with the dual-injection technique of radiocolloid/blue dye can successfully discriminate the sentinel lymph node. The aim of this study was to investigate the potential of ^99mTc-EB as an agent to map the lymphatic system in an ovine model. Methods  Doses of ^99mTc-EB (23 MBq) containing EB dye (4 mg) were administered intradermally to the limbs of four anesthetized sheep, and they were then imaged over 20–30 min using a gamma camera. The study protocol was repeated using ^99mTc-antimony trisulfide colloid (ATC) and Patent Blue V dye. The lymph nodes (popliteal, inguinal, and iliac for hind limbs or prescapular for fore limbs) were identified with a gamma probe during the operative exposure, then dissected and counted in a large volume counter. Results  Simple and complex (dual) drainage patterns were visible on the scans, and the sentinel node was more radioactive than higher tier nodes in a chain, for both radiotracers. For ^99mTc-EB, maximum radioactive uptake was achieved at 3–6 min for popliteal lymph nodes, 12–14 min for iliac nodes, and 13–14 min for prescapular nodes. ^99mTc-ATC resulted in maximum radioactive uptake at 4–6 min for popliteal lymph nodes, 13 min for an inguinal node, 13–20 min for iliac nodes, and 18 min for a prescapular node. Following ^99mTc-EB injection, 15/15 lymph nodes harvested were all radioactive and blue. For ^99mTc-radiocolloid/Patent Blue V injection, 8/14 nodes were radioactive and blue, and 6/14 nodes were radioactive only. Conclusions  The soluble radiotracer ^99mTc-EB appeared to be a useful lymphoscintigraphic agent in sheep, in which radioactive counts from superficial lymphatic channels and lymph nodes were sufficient for planar imaging. In comparison with ^99mTc-antimony trisulfide colloid, both tracers discriminated the sentinel lymph node up to 50 min after administration; however, ^99mTc-EB had the advantage of providing radioactive (gamma probe) and color signals simultaneously during the operative exposure.     

T-cell/histiocyte-rich large B-cell lymphoma: a heterogeneous entity with derivation from germinal center B cells

T-cell/histiocyte-rich large B-cell non-Hodgkin's lymphoma (THRLBCL) is an unusual morphologic variant of diffuse large B-cell lymphoma. We reviewed 30 cases of THRLBCL to evaluate its heterogeneity based on morphologic, immunophenotypic, and genetic features. Cases were classified according to the appearance of the large neoplastic B cells into three morphologic variants: 1) lymphocytic and histiocytic (L&H-like) (resembling the L&H cells of nodular lymphocyte predominance Hodgkin's lymphoma (14 cases); 2) centroblast (or immunoblast)-like (10 cases), and 3) Reed-Sternberg cell-like (resembling the neoplastic cells of classic Hodgkin's lymphoma) (6 cases). We used a panel of immunohistochemical stains, including those with specificity for germinal center B cells: CD20, CD79a, CD30, CD15, epithelial membrane antigen, BCL-2, BCL-6, and CD10. The /JH polymerase chain reaction assay was further performed to investigate a relationship to follicular lymphoma. The results were correlated with Epstein-Barr virus status as determined by staining for latent membrane protein and EBER-1 in situ hybridization. All cases were of B-cell immunophenotype with strong surface CD20 reactivity in the neoplastic large lymphoid cells, although CD79a was more inconsistently and weakly expressed (10 of 17). Nuclear positivity for the BCL-6 protein was detected in the tumor cells in 26 of 29 (90%) cases. However, differences in expression of other antigens were encountered in the histologic subtypes. Epithelial membrane antigen positivity, a feature often seen in nodular lymphocyte predominance Hodgkin's lymphoma, was observed in 11 of 30 (37%) cases and was most commonly seen in cases with L&H cell morphology (8 of 14; 57%). CD30 expression was observed in 9 of 30 (30%) cases but was most frequent in cases with Reed-Sternberg-like morphology (3 of 6 [50%]). CD10 expression was infrequent overall (3 of 29; 10%), with 2 of 3 positive cases identified in the centroblastic group. The overall rarity of positivity for CD10, BCL-2 (3 of 22; 13%), and -2 JH rearrangement (1 of 28; 4%) indicates a lack of connection to follicular lymphoma for all subtypes. The three cases that were negative for BCL-6 protein were LMP-1 positive and EBER-1 positive by in situ hybridization, and 2 of 3 had neoplastic cells with Reed-Sternberg-like morphology. These results demonstrate that although a large proportion of THRLBCL represent tumors of germinal center B cell derivation, they exhibit a diversity of morphologic and immunophenotypic features. A subset of THRLBCL may be related to nodular lymphocyte predominance Hodgkin's lymphoma. A small percentage show features closely resembling classic Hodgkin's lymphoma and could be considered a variant of grey zone lymphoma.     

Reduced renal function and benefits of treatment in cystinuria vs other forms of nephrolithiasis

A significant study from the USA compares cystine stone formers and routine stone formers; the former group had a higher requirement for therapeutic procedures, but this was less if they took chelating agents, although remaining higher than in the latter group. Other interesting findings are also presented. OBJECTIVE: First, to compare two types of stone formers (SF), those with cystinuria and those without, for effects of treatments for stones, as cystinuria leads to recurrent stones that are difficult to fragment with shock-wave lithotripsy, and there is disagreement about the efficacy of current treatments. Second, to compare these two groups with respect to blood pressure (BP) and renal function, as cystine stones may be associated with more morbidity than are routine stones. PATIENTS AND METHODS: Fifty-two cystinuric patients (cystine SF) entering our programme since 1970 were compared with 3215 SF without cystinuria (routine SF), of whom 114 had a single functioning kidney (routine SF + nephrectomy). All patients had three 24-h urine and blood samples taken to determine the risk of stones before their first clinic visit; these studies were repeated after therapy was initiated, and at regular intervals to monitor therapy. Cystine was measured in the urine samples of the cystine SF. All stone-related procedures were recorded, and BP measured at clinic visits. Creatinine clearances (CCr) were calculated from each set of serum and urine values. Cystine supersaturation (SS) was directly measured in 16 urine samples collected before treatment and 13 afterward. RESULTS: Patients were treated with increased fluid intake, potassium alkali and chelating agents such as alpha-mercapto-propionyl-glycine, as needed. The mean (sd) CCr, corrected for age and gender, was significantly lower at entry in cystine SF than in routine SF, at 91 (6) vs 160 (1) L/day, respectively (P < 0.001), and remained so at the last CCr. Neither systolic nor diastolic BP, similarly corrected, differed between the groups, but cystine SF had significantly more procedures, corrected for time at risk, before treatment than did routine SF, at 4.0 (0.4) vs 1.86 (0.06), respectively (P < 0.001); time-adjusted procedures decreased significantly in both groups during treatment, but remained higher in cystine SF, at 0.88 (0.14) vs 0.23 (0.02), respectively, (P < 0.001). Urine volume and pH were significantly higher in cystine SF than in routine SF, both before and during treatment. Cystine SS decreased during treatment, consistent with the increase in urine volume and decline in procedure rates during treatment. CONCLUSION: Cystine SF have significantly higher procedure rates than routine SF, but procedure rates decline during therapy, although they remain higher than in routine SF. The lower CCr in cystinurics suggests that treatment to prevent stone recurrence and the need for procedures is particularly important, and emphasizes the need for a close follow-up. Use of cystine SS measurements may allow closer monitoring of the effect of treatment on the risk of stone recurrence.     

MRI visible Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> polypropylene mesh: 3D reconstruction of spatial relation to bony pelvis and neurovascular structures

Introduction and hypothesis

To demonstrate mesh magnetic resonance imaging (MRI) visibility in living women, the feasibility of reconstructing the full mesh course in 3D, and to document its spatial relationship to pelvic anatomical structures.

Methods

This is a proof of concept study of three patients from a prospective multi-center trial evaluating women with anterior vaginal mesh repair using a MRI-visible Fe₃O₄ polypropylene implant for pelvic floor reconstruction. High-resolution sagittal T2-weighted (T2w) sequences, transverse T1-weighted (T1w) FLASH 2D, and transverse T1w FLASH 3D sequences were performed to evaluate Fe₃O₄ polypropylene mesh MRI visibility and overall post-surgical pelvic anatomy 3 months after reconstructive surgery. Full mesh course in addition to important pelvic structures were reconstructed using the 3D Slicer® software program based on T1w and T2w MRI.

Results

Three women with POP-Q grade III cystoceles were successfully treated with a partially absorbable MRI-visible anterior vaginal mesh with six fixation arms and showed no recurrent cystocele at the 3-month follow-up examination. The course of mesh in the pelvis was visible on MRI in all three women. The mesh body and arms could be reconstructed allowing visualization of the full course of the mesh in relationship to important pelvic structures such as the obturator or pudendal vessel nerve bundles in 3D.

Conclusions

The use of MRI-visible Fe₃O₄ polypropylene meshes in combination with post-surgical 3D reconstruction of the mesh and adjacent structures is feasible suggesting that it might be a useful tool for evaluating mesh complications more precisely and a valuable interactive feedback tool for surgeons and mesh design engineers.

     

Isolated Limb Infusion for Malignant Melanoma: Predictors of Response and Outcome

Purpose

Isolated limb infusion (ILI) is an alternative to isolated limb perfusion (ILP) for the treatment of unresectable limb melanoma recurrence. The aims of this study were to determine the response rates of unresectable local and/or in-transit melanoma of the upper or lower limb to ILI and to identify factors predictive of survival.

Methodology

A prospective database identified 74 patients (35 male and 39 female) with local and/or in-transit melanoma recurrence without metastatic disease who underwent hyperthermic ILI with melphalan at a single institution between January 1996 and December 2008. Three patients could not be evaluated for response. Median follow-up was 34 months.

Results

Of the 74 patients, the majority had N2c disease (57/74, 67%), while 17/74 (33%) patients had N3 disease. Median maximum temperature achieved was 38.1°C and median tourniquet time was 32.5 min. Wieberdink III/IV complications occurred following 7/74 (10%) ILI and were associated with higher limb volumes and higher total melphalan dose. Complete response (CR) was seen following 17/71 (24%) ILI and the partial response rate was 30% (22/71). The median duration of CR was 43 months. Univariable analyses found that limb volume >8.0 l and maximum limb temperature >38.5°C were the only independent factors predictive for a CR following ILI. Multivariate analyses identified CR and positive lymph nodes as the only independent prognostic factors for melanoma-specific survival.

Conclusions

Patients who obtain CR have significantly improved survival compared with nonresponders. The challenge remains to improve CR rates and prospectively identify responders.     

A health economic analysis of the use of rhBMP-2 in Gustilo–Anderson grade III open tibial fractures for the UK, Germany, and France

The purpose of this study was to determine the cost savings from a societal perspective for recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in grade III A and B open tibial fractures treated with a locked intramedullary nail and soft-tissue management in the UK, Germany, and France. Health care system costs (direct health care costs) and costs for productivity losses (indirect health care costs) were calculated using the raw data from the Bone Morphogenetic Protein Evaluation Group in Surgery for Tibial Trauma “BESTT study”. Return-to-work time for estimation of productivity losses was assumed to correspond with the time of fracture healing. For calculation of secondary interventions costs and productivity losses the respective 2007/2008 national tariffs for surgical procedures and average national wages for the UK, Germany, and France were used. For a 1 year perspective, overall treatment costs per patient after the initial surgery of the control vs. the rhBMP-2 group were €44,757 vs. €36,847 for the UK, €50,197 vs. €40,927 for Germany and €48,766 vs. €39,474 for France in favour of rhBMP-2 with overall savings overall savings per case of rhBMP-2 treatment of €7911 for the UK, €9270 for Germany, and €9291 for France which was mainly due to reduced productivity losses by significant faster fracture healing in the rhBMP-2 group (p = 0.01). These savings largely offset the upfront price of rhBMP-2 of €2266 (£1790) in the UK, €2970 in Germany, and €2950 in France. Total net savings can be estimated to be €9.6 million for the UK, €14.5 million for Germany, and €11.4 million for France. The results depend on the methodology used particularly for calculation of productivity losses and return-to-work time which was assumed to correspond with fracture healing time. In summary, despite the apparent high direct cost of rhBMP-2 in grade III A and B open tibial fractures, at a national level there are net cost savings from a societal perspective for all three countries.     

Reliability among clinicians diagnosing low back-related leg pain

Purpose

To investigate agreement and reliability among clinicians when diagnosing low back-related leg pain (LBLP) in primary care consulters.

Methods

Thirty-six patients were assessed by one of six physiotherapists and diagnosed as having either leg pain due to nerve root involvement (sciatica) or referred leg pain. Assessments were video recorded. In part one, the physiotherapists each viewed videos of six patients they had not assessed. In part two, videos were viewed by another six health professionals. All clinicians made an independent differential diagnosis and rated their confidence with diagnosis (range 50–100 %).

Results

In part one agreement was 72 % with fair inter-rater reliability (K = 0.35, 95 % CI 0.07, 0.63). Results for part two were almost identical (K = 0.34, 95 % CI 0.02, 0.69). Agreement and reliability indices improved as diagnostic confidence increased.

Conclusion

Reliability was fair among clinicians from different backgrounds when diagnosing LBLP but improved substantially with high confidence in clinical diagnosis.

     

Alterations in midline cortical thickness and gyrification patterns mapped in children with 22q11.2 deletions

The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome)is a neurogenetic condition associated with visuospatial deficits,as well as elevated rates of attentional disturbance, mood disorder,and psychosis. Previously, we detected pronounced cortical thinningin superior parietal and right parieto-occipital cortices inpatients with this syndrome, regions critical for visuospatialprocessing. Here we applied cortical pattern-matching algorithmsto structural magnetic resonance images obtained from 21 childrenwith confirmed 22q11.2 deletions (ages 8–17) and 13 demographicallymatched comparison subjects, in order to map cortical thicknessacross the medial hemispheric surfaces. In addition, corticalmodels were remeshed in frequency space to compute their surfacecomplexity. Cortical maps revealed a pattern of localized thinningin the ventromedial occipital–temporal cortex, criticalfor visuospatial representation, and the anterior cingulate,a key area for attentional control. However, children with 22q11.2DSshowed significantly increased gyral complexity bilaterallyin occipital cortex. Regional gray matter volumes, particularlyin medial frontal cortex, were strongly correlated with bothverbal and nonverbal cognitive functions. These findings suggestthat aberrant parieto-occipital brain development, as evidencedby both increased complexity and cortical thinning in theseregions, may be a neural substrate for the deficits in visuospatialand numerical understanding characteristic of this syndrome.