Increased morbidity and mortality in elderly patients with lower extremity trauma and associated injuries: A review of 420,066 patients from the national trauma database.

INTRODUCTION: There is a paucity of research addressing the morbidity and mortality associated with polytrauma in elderly patients. This study aimed to compare the outcomes of elderly trauma patients with an isolated lower extremity fracture, to patients lower extremity fractures and associated musculoskeletal injuries. METHODS: This study is a retrospective review from the National Trauma Database (NTDB) between 2008 and 2014. ICD 9 codes were used to identify patients 65 years and older with lower extremity fractures. Patients were categorize patients into three sub groups: patients with isolated lower extremity fractures (ILE), patients with two or more (multiple) lower extremity fractures (MLE) and, patients with at least one upper and at least one lower extremity fracture (ULE). Groups were stratified into patients age 65-80 and patients >80 years of age. RESULTS: A total 420,066 patients were included in analysis with 356,120 ILE fracture patients, 27,958 MLE fracture patients, and 35,988 ULE fracture patients. The MLE group reported the highest dispatch to ACS level 1 trauma centers at 31.8% followed by the ULE group at 28.5% and the ILE group at 24.7% of patients (p<0.001). The overall rate of complications was highest in the MLE group followed by the ULE and then the ILE group (41.4%, 40.3%, 36.1%, respectively p<0.001). Motility rates in patients >80 years old in the MLE group and ULE group were similar (1.483 vs 1.4432). However, in the 65-80 year group the odds of mortality was 1.260 in the MLE group and 1.450 in the ULE group (p<0.001), such that the odds of mortality after sustaining a MLE fracture increases with age, whereas this effect was not seen in the ULE group. CONCLUSION: Patients who sustained MLE and ULE fractures, had increased mortality, complications and in hospital care requirements as compared to patients with isolated lower extremity injuries. These outcomes are comparable between ULE and MLE fracture patients over the age of 80 however patients 65-80 with ULE fractures had increased mortality as compared patients 65-80 with MLE fractures. Understanding the unique considerations and requirements of elderly trauma patients is vital to providing successful outcomes.

Biomechanical properties of volar hybrid and locked plate fixation in distal radius fractures.

PURPOSE: We compare the biomechanical properties of a volar hybrid construct to an all-locking construct in an osteoporotic and normal comminuted distal radius fracture model. METHODS: Groups of 28 normal, 28 osteoporotic, and 28 over-drilled osteoporotic left distal radius synthetic bones were used. The normal group consisted of synthetic bone with a standard foam core. The osteoporotic group consisted of synthetic bone with decreased foam core density. The over-drilled osteoporotic group consisted of synthetic bone with decreased foam core density and holes drilled with a 2.3 mm drill, instead of the standard 2.0 mm drill, to simulate the lack of purchase in osteoporotic bone. Within each group, 14 synthetic bones were plated with a volar locking plate using an all-locking screw construct, and 14 synthetic bones were plated with a volar locking plate using a hybrid screw construct (ie, both locking and nonlocking screws). A 1-cm dorsal wedge osteotomy was created with the apex 2 cm from the volar surface of the lunate facet. Each specimen was mounted to a materials testing machine, using a custom-built, standardized axial compression jig. Axial compression was delivered at 1 N/s over 3 cycles from 20 N to 100 N to establish stiffness. Each sample was stressed to failure at 1 mm/s until 5 mm of permanent deformation occurred. RESULTS: Our results show no difference in construct stiffness and load at failure between the all-locking and hybrid constructs in the normal, osteoporotic, or over-drilled osteoporotic synthetic bone models. All specimens failed by plate bending at the osteotomy site with loss of height. CLINICAL RELEVANCE: Although volar locking plates are commonly used for the treatment of distal radius fractures, the ideal screw configuration has not been determined. Hybrid fixation has comparable biomechanical properties to all locking constructs in the fixation of metaphyseal fractures about the knee and shoulder and might also have a role in the fixation of distal radius fractures.

The combination method using magnetic beads and a magnet helps sustain the number of donor BM cells after intra-BM injection, resulting in rapid hematopoietic recovery.

We have developed a new BMT method, intra-BM-BMT (IBM-BMT), in which donor BM cells (BMCs) are directly injected into the recipient's BM, resulting in a rapid recovery of donor hematopoiesis and a reduction in the severity of GVHD. In the present experiment, we attempted to retain the number of injected BMCs using magnetic beads and a magnet. The BMCs of donor mice were conjugated with magnetic beads, and these cells were then injected into the BM of recipient mice with a magnet (magnet-IBM group) and compared with conventional IBM-BMT without a magnet (IBM group). A significantly higher number of transplanted cells were detected in the injected BM in the magnet-IBM group. We next carried out day-12 colony-forming units of spleen (CFU-S) assays to examine the early stage of hematopoiesis of the injected host hematopoietic stem cells after IBM-BMT. The spleens of mice in the magnet-IBM group showed considerably higher CFU-S counts than those in the IBM group. Excellent reconstitution of donor hematopoietic cells in the magnet-IBM group was observed 1 month after IBM-BMT. These results suggest that the IBM-BMT using the combination of magnetic beads and a magnet is superior to the conventional IBM-BMT.

Treating ulcerative colitis by Adacolumn therapeutic leucocytapheresis: clinical efficacy and safety based on surveillance of 656 patients in 53 centres in Japan.

BACKGROUND/AIM: The Adacolumn selectively depletes granulocytes and monocytes/macrophages, which are thought to be part of the immunopathogenesis of ulcerative colitis. This work aims at evaluating the safety and clinical efficacy of the Adacolumn in patients with ulcerative colitis in large population-based data sets. METHODS: The Adacolumn post marketing surveillance in Japan was undertaken on 697 patients in 53 medical institutions over 7 years from 29 October 1999 to 28 October 2006. Clinical efficacy and safety data were provided by patients' physicians in the participating institutes. RESULTS: Safety was evaluated in all the 697 patients and efficacy in 656 patients. At entry, 92% of the patients were on salicylates, 74% on prednisolone and only 9% on immunomodulators. Approximately 40% of patients had severe ulcerative colitis and over 70% had ulcerative colitis that was refractory to conventional medications. There was no serious adverse events; mild to moderate adverse events were seen in 7.7% of the patients. The overall response (remission or significantly improved) was 77.3%; the remission rate based on clinical activity index was 71.1%, while 17.1% remained unchanged and 5.6% worsened. Patients were subgrouped into severe, moderate and mild ulcerative colitis based on clinical activity index (n=578), the response rates were 63.2%, 65.7% and 80.4%, respectively (P<0.001). Endoscopic assessment of efficacy showed very significant mucosal healing, Matts' endoscopic index improved from 3.2+/-0.04 to 2.1+/-0.7 (n=219, P<0.001); reduction in prednisolone dose (P<0.0001); leucocyte count (n=358, P<0.0001) and C-reactive protein (n=314, P<0.0001). Patients who received > or =6 Adacolumn sessions (n=319) did better than patients who received < or =5 sessions (n=188, P=0.004) and multivariate logistic regression analysis revealed that baseline granulocyte count was the strongest predictor of clinical response to Adacolumn (P=0.0191, odds ratio 1.151). CONCLUSION: This post marketing surveillance provides the largest ever efficacy and safety data on the Adacolumn therapeutic leucocytapheresis in patients with ulcerative colitis. As a non-pharmacologic treatment for patients with active ulcerative colitis most of whom were refractory to conventional drug therapy, the observed efficacy was very significant. Baseline granulocyte count was convincingly an independent predictor of clinical response.

Efficacy of intravitreal injection of bevacizumab for severe retinopathy of prematurity: a pilot study.

AIM: The aim of the study was to evaluate the short-term efficacy of intravitreal injections of bevacizumab for severe retinopathy of prematurity (ROP). METHODS: A retrospective chart review was conducted of 23 consecutive eyes (stage 3, three eyes; 4A, 18 eyes; 4B, two eyes) of 14 patients with vascularly active ROP considered at high risk for progression or development of tractional retinal detachment despite conventional laser ablation therapy. Patients received an intravitreal injection of bevacizumab (0.5 mg), either as the initial treatment (15 eyes) or at the end of vitrectomy (eight eyes). RESULTS: After injection of bevacizumab as the initial treatment, reduced neovascular activity was seen on fluorescein angiography in 14 of 15 eyes. In three eyes, a tractional retinal detachment developed or progressed after bevacizumab injection. No other ocular or systemic adverse effects were identified. Vitrectomy was performed in 20 eyes and the retina was reattached after one surgery in 18 eyes. Multiple surgeries were necessary in two eyes, resulting in retinal reattachment. CONCLUSION: There results suggest that intravitreal injection of bevacizumab seems to be associated with reduced neovascularisation without apparent ocular or systemic adverse effects, and is thus beneficial for treating severe ROP that is refractory to conventional laser therapy.

Enhanced exudation of fibrinogen into the perivascular space in acute inflammation triggered by neutrophil migration.

OBJECTIVE: The present experiments were performed to ascertain whether or not all plasma components are extravasated when vascular permeability is increased. ANIMALS: Male Sprague-Dawley strain rats (specific pathogen-free) 8 weeks old (for histamine exudation) or 9-10 weeks old (for carrageenin pleurisy) were used. METHODS: Histamine or A-carrageenin was injected into the rat right pleural cavity to induce rat pleurisy. Protein components in the inflammatory exudate and plasma were separated by high performance liquid chromatography. Coagulation time was assessed, and the fibrinogen levels in the pleural exudate were determined by thrombin time. The fibrinogen levels were also visualized by immunoblot analysis. Tumor necrosis factor-alpha (TNF-alpha, 0.4 microg/rat, intrapleurally), anti-rat CD18 monoclonal antibody (anti-CD18 antibody, 1 mg/kg, i. v.) and granulocyte-colony stimulating factor (G-CSF, 100 microg/kg, s.c. twice daily for 4 days) were used. RESULTS: In the histamine-induced extravasation, the level of plasma protein components with large molecules over 900 kD in the exudate was 62% of that in the rat's own plasma. The amount of fibrinogen in the pleural exudate was 1/8 of that in the plasma and was faintly detected in immunoblot analysis, but it was clearly detected after the treatment of rats with TNF-alpha. In rat carrageenin pleurisy, fibrinogen was hardly detected in immunoblot analysis in the exudate collected 0.5 h after carrageenin, when neutrophils did not migrate into the exudate. However, it was clearly present after neutrophil migration started 2 h later The increase in the neutrophil counts in the exudate caused by G-CSF enhanced the fibrinogen level in the exudate, whereas intravenous injection of anti-CD18 antibody suppressed the fibrinogen level in immunoblot analysis. CONCLUSIONS: Venular permeability increase in the rat histamine exudation induced minimal extravasation of plasma proteins with large molecules, such as fibrinogen, while fibrinogen molecule was detected in rat carrageenin-injected pleurisy, when neutrophil diapedesis occurred. Thus, only when neutrophils started to migrate into the perivascular space was fibrinogen clearly detected in the exudate.

[Characteristics of home care patients with intractable neurological diseases (Nanbyo) in Tokyo].

The purpose of this study was to identify the characteristics of home care of patients with intractable neurological diseases. A survey was conducted of members of Tokyo Medical Association who were home visit doctors. They responded to questions about their patients who have suffered from either Parkinson's disease (PD), spinocerebellar degeneration (SCD), or amyotrophic lateral sclerosis (ALS), and whose home care have been supported by the care system for at least three months. Of 205 survey questionnaires collected, 198 were effective to be analyzed. The sample consisted of 105 patients with PD (53.0%), 63 patients with SCD (31.8%), and 30 patients with ALS (15.2%). The mean age of the PD was 75.5 years with a range of 53 to 90, SCD was 66.5 years with a range of 39 to 88, and ALS was 58.7 years with a range of 42 to 86. The major findings in this study were as follows: 1) The patients who had one or more medical equipment installed at the beginning of home care were 30% of ALS, 9% of PD and 18% of SCD. As time elapsed, patients who needed to have some medical equipment installed increased in ALS greater than in PD and SCD. 2) The home doctors predicted that the condition of 37% of ALS patients, 9% of PD, and 8% of SCD would probably be deteriorating within one month. 3) Of the 30 patients with ALS, 47% experienced hospitalization three times or more compared to 27% of PD and 21% of SCD. The most prevalent reason for hospitalization for ALS was respite of caregivers, PD and SCD, however, were hospitalized for control of prescription, a change for the worse, or treatment of other diseases. 4) Ninety percent of ALS caregivers felt extremely tired or slightly tired. Their home doctors responded that 83% of ALS caregivers did their best in caregiving. 5) ALS patients utilized social resources such as volunteers, care workers, services of supply and maintenance of medical equipment, and emergency care for 24 hours more than SCD and PD. In the conclusion, ALS patients experienced the highest hospitalization of the three diseases and respite of family caregivers was necessary. They showed a higher utilization of various social resources than other diseases. It is important to consider these characteristics of home care patients by diseases in order to prepare and develop the necessary support system of home care for the intractable neurological patients.

A novel method for determination of alpha1,6fucosyltransferase activity using a reducing oligosaccharide from egg yolk as a specific acceptor.

A new method for determination of alpha1,6fucosyltransferase activity has been described. Recently, the disialyl-biantennary undecasaccharide was prepared in high yield from egg yolk [(1996), Carbohydr Lett 2: 137-42]. By treatment of this oligosaccharide with neuraminidase and beta-galactosidase, we readily obtained an asialo-agalacto-biantennary heptasaccharide (GlcNAcbeta 1,2Manalpha1,6[GlcNAcbeta1,2Manalpha1,3]Manbeta1 ,4GlcNAcbeta1,4GlcNAc). Using this asialo-agalacto-oligosaccharide as an acceptor, fucosyltransferases from human plasma and extracts of various human hepatoma cell lines were assayed in the presence of GDP-[3H]fucose. The reaction mixture was applied to a column of GlcNAc-binding, Psathyrella velutina lectin coupled gel. All the fucosylated acceptor were bound to the column which was eluted with 50 mM GlcNAc. Structural analyses revealed that only the innermost GlcNAc residue of the acceptor was fucosylated through an alpha1,6-linkage, and the oligosaccharide prepared could be used as a specific acceptor for alpha1,6fucosyltransferase. The present method was used to screen plasma alpha1,6fucosyltransferase in several patient groups, and significantly elevated activities were found in samples from patients with liver diseases, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Poststatin, a novel inhibitor of bradykinin-degrading enzymes in rat urine.

Incubation of bradykinin with rat urine resulted in the successive degradation of bradykinin to bradykinin-(1-8), bradykinin-(1-7) and bradykinin-(1-6). In contrast, in rat plasma, bradykinin was degraded via either bradykinin-(1-8) or bradykinin-(1-7) to bradykinin-(1-5). Phosphoramidon (1 mM) partially inhibited the degradation of bradykinin by rat urine, as well as the conversion of bradykinin-(1-7) to bradykinin-(1-6). D,L-2-Mercaptomethyl-3-guanidinoethylthiopropanoic acid (1 mM) and captopril (1 mM) did not have a significant effect on any of the degradation steps in rat urine. In contrast, all of the degradation steps in urine, namely, from bradykinin to bradykinin-(1-8), from bradykinin-(1-8) to bradykinin-(1-7) and from bradykinin-(1-7) to bradykinin-(1-6), were markedly inhibited by poststatin (1 mM), even though this compound was reported originally to be a novel inhibitor of post-proline cleaving enzyme. Poststatin (1 mM) did not inhibit the degradation of bradykinin in rat plasma. These results indicate that poststatin is an effective inhibitor of kinin-degrading enzyme in rat urine.

A stable metabolite, Arg-Pro-Pro-Gly-Phe, of bradykinin in the degradation pathway in human plasma.

Degradation of bradykinin (BK) in human plasma was investigated by searching for a stable metabolite as a marker of kinin release in vivo. BK, incubated with diluted plasma, was degraded to des-Arg9-BK (des-9-BK), des-Phe8-Arg9-BK (des-8,9-BK) and Arg-Pro-Pro-Gly-Phe ([1-5]BK). Des-9-BK was degraded to [1-5]BK without an increase in des-8,9-BK, and des-8,9-BK was also degraded to [1-5]BK. D,L-2-Mercaptomethyl-3-guanidinoethyl-thiopropanoic acid inhibited the formation of des-9-BK from BK, whereas captopril inhibited the formation of des-8,9-BK from BK as well as that of [1-5]BK from des-9-BK or des-8,9-BK. The half lives of BK, des-9-BK, des-8,9-BK and [1-5]BK under the present experimental conditions were 60 min, 90 min, 14 min and 4.2 hr, respectively. Among the metabolites, [1-5]BK was the most stable one and may be used as a marker for BK production in vivo.