Treatment of distal tibial metaphyseal fractures: Plating versus shortened intramedullary nailing

BACKGROUND: Fractures in the distal tibial metaphysis are more complicated to treat than diaphyseal fractures. We compared treatment with plating to treatment with shorted intramedullary (IM) nailing. METHODS: Patients with AO type 43A fractures were treated with plate fixation (group A, n=14) or shortened IM nailing (group B, n = 13). We compared postoperative radiographic deformities, functional results (Iowa ankle scores), and symptoms (Olerud and Molander ankle scores). RESULTS: All fractures had healed at final follow-up (mean, 33 month). Mean union times were 27.8 week (range, 18-36 week) in group A and 22.6 week (range, 18-30 week) in group B (P<0.05). Mean postoperative valgus angulations were larger in group B (3.7 degrees ) than in group A (0.5 degrees ) (P<0.05). However, malunions did not differ between groups (P<0.05). Functional results and postoperative symptoms were similar. CONCLUSIONS: Both plate fixation and shortened IM nailing were effective for treating distal tibial metaphyseal fractures.     

Sodium arsenite potentiates the clastogenicity and mutagenicity of DNA crosslinking agents

To see if sodium arsenite enhances the clastogenicity and the mutagenicity of DNA crosslinking agents, Chinese hamster ovary (CHO) cells and human skin fibroblasts were exposed to cis-diamminedichloroplatinum (II) (cis-Pt(II)) or 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet light (UVA) and then to sodium arsenite. The results indicate that the clastogenicity of cis-Pt(II) and 8-MOP plus UVA are enhanced by the post-treatment with sodium arsenite. Chromatid breaks and exchanges are predominantly increased in doubly treated cells. Furthermore, the mutagenicity of cis-Pt(II) at the hypoxanthine-guanine phosphoribosyl transferase locus is also potentiated by sodium arsenite in CHO cells.     

Monoclonal antibodies against Trichomonas vaginalis

Spleen lymphocytes obtained from mice immunized with Trichomonas vaginalis ATCC 30001 were fused with P3-X63-Ag8-653 mouse myeloma in order to produce hybridoma-secreting antibodies against T. vaginalis associated antigens. Six hybridoma cloned cell lines were established; three produced IgG1, two produced IgG2a, and one produced IgM monoclonal antibody. These six monoclonal antibodies showed binding to seven isolated strains of T. vaginalis but did not bind to Giardia lamblia. Three of those monoclonal antibodies did not bind to Tritrichomonas foetus. These anti-trichomonal monoclonal antibodies should prove to be of great value as diagnostic and research reagents.     

Zinc Status Alters Alzheimer's Disease Progression through NLRP3-Dependent Inflammation

Alzheimer''s disease is a devastating neurodegenerative disease with a dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing Alzheimer''s disease. Zinc deficiency is the most prevalent malnutrition in the world and may be a risk factor for Alzheimer''s disease potentially through enhanced inflammation, although evidence for this is limited. Here we provide epidemiological evidence suggesting that zinc supplementation was associated with reduced risk and slower cognitive decline, in people with Alzheimer''s disease and mild cognitive impairment. Using the APP/PS1 mouse model of Alzheimer''s disease fed a control (35 mg/kg zinc) or diet deficient in zinc (3 mg/kg zinc), we determined that zinc deficiency accelerated Alzheimer''s-like memory deficits without modifying amyloid β plaque burden in the brains of male mice. The NLRP3-inflammasome complex is one of the most important regulators of inflammation, and we show here that zinc deficiency in immune cells, including microglia, potentiated NLRP3 responses to inflammatory stimuli in vitro, including amyloid oligomers, while zinc supplementation inhibited NLRP3 activation. APP/PS1 mice deficient in NLRP3 were protected against the accelerated cognitive decline with zinc deficiency. Collectively, this research suggests that zinc status is linked to inflammatory reactivity and may be modified in people to reduce the risk and slow the progression of Alzheimer''s disease.SIGNIFICANCE STATEMENT Alzheimer''s disease is a common condition mostly affecting the elderly. Zinc deficiency is also a global problem, especially in the elderly and also in people with Alzheimer''s disease. Zinc deficiency contributes to many clinical disorders, including immune dysfunction. Inflammation is known to contribute to the risk and progression of Alzheimer''s disease; thus, we hypothesized that zinc status would affect Alzheimer''s disease progression. Here we show that zinc supplementation reduced the prevalence and symptomatic decline in people with Alzheimer''s disease. In an animal model of Alzheimer''s disease, zinc deficiency worsened cognitive decline because of an enhancement in NLRP3-driven inflammation. Overall, our data suggest that zinc status affects Alzheimer''s disease progression, and that zinc supplementation could slow the rate of cognitive decline.     

Is hyperbaric oxygen therapy indispensable for saving mutilated hand injuries?

Mutilated hand injuries are a profound challenge to the plastic surgeon, and such injuries often lead to limb loss and severe functional impairment. Hyperbaric oxygen therapy (HBOT) appears to counteract tissue hypoxia and stimulate acute wound healing. This study was performed to evaluate the efficacy of HBOT as an adjunctive therapy in patients with a mutilated hand injury. Between January 2006 and December 2014, 45 patients with a mutilated hand injury were enrolled. After reconstruction or revascularisation, patients underwent 120 minutes of HBOT with oxygen at 2·5 atmospheres absolute while breathing 100% oxygen. Outcomes such as amputee survival and surgery‐related complications were recorded. The patients were 38 men and 7 women with average age of 37·2 years (range 18–62). The mean defect area was 131·5 cm² (range 40–300). Most patients experienced a pure crush injury (53%). The average number of operations from the initial debridement to the first reconstruction was 3·8 (range 1–6). A total of 33 patients (73%) underwent replantation during the initial reconstruction. For flap coverage, most patients received a free flap using an anterolateral thigh flap (18 patients) or local flap using an abdomen/groin flap (nine patients). The average time from the first reconstruction or revascularisation to the first HBOT was 6·5 hours (range 2–12). The average number of HBOT sessions was 9·1 (range 6–14 sessions). The survival rate of the replanted fingers was 81%, and the survival rate of the palms was 100%. Most complications in the initial reconstruction involved partial loss of an avulsed flap, and most complications in the chronic stage (≥3 months) involved scar contracture. When combined with delicate microsurgery, early intervention using adjunctive HBOT was effective in preserving partially viable tissue and restoring hand function in patients with a mutilated hand injury.     

Hospitalized osteoporotic vertebral fracture increases the risk of stroke: A population‐based cohort study

The association between osteoporosis and cardiovascular diseases has been demonstrated. Higher cardiovascular risk has also been correlated with vertebral fractures. However, the association between osteoporotic vertebral fracture and the possibly higher risk of stroke remains uncertain. This study aimed to evaluate the incidence, risk, and type of stroke in patients with osteoporotic vertebral fracture. Patients with osteoporotic vertebral fracture were identified (n = 380) and 10 age‐ and sex‐matched controls per case (comparison group, n = 3795) were chosen from a nationwide representative cohort of 999,997 people from 1998 to 2005. Both groups were followed‐up for stroke events for 3 years, matched by propensity scores with adjustments for covariates such as comorbidities (ie, hypertension, diabetes, arrhythmia, or coronary heart diseases) and exposure to medications (ie, aspirin, lipid lowering drug, or nitrates), and assessed by Kaplan‐Meier and Cox regression analyses. The incidence rate of stroke in the osteoporotic vertebral fracture group (37.5 per 1000 person‐years; 95% confidence interval [CI], 27.5–51.2) was significantly higher than in the comparison group (14.0 per 1000 person‐years; 95% CI, 12.0–16.4, p < 0.001). Stroke was more likely to occur in the osteoporotic vertebral fracture patients than in the normal controls (crude hazard ratio [HR] 2.68, 95% CI 1.89–3.79, p < 0.001; adjusted HR 2.71, 95% CI 1.90–3.86, p < 0.001). In conclusion, patients with osteoporotic vertebral fracture have a higher risk of stroke (ie, both ischemic and hemorrhagic) and require stroke prevention strategies. © 2013 American Society for Bone and Mineral Research.     

Use of split‐thickness plantar skin grafts in the management of leg and foot skin defects

The basic principle of donor site selection is to take skin from areas that will heal with minimal scarring while balancing the needs of the recipient site. For skin loss from the lower legs and feet, the most common harvest site for split‐thickness skin grafts is the anterior or posterior thigh; grafts from the plantar areas have been mostly used to cover the volar aspect of digits and palms. Between September 2015 and September 2017, 42 patients with areas of skin loss on the legs or feet were treated with plantar skin grafts because of their cosmetic benefits and the convenience of the surgical procedure and postoperative wound care. Our technique of harvesting a single layer of split‐thickness skin graft (0.014 in. thick) from a non‐weight‐bearing area of the foot of the injured leg is simple and provided good functional and cosmetic outcomes at both the donor and recipient sites. All patients were very satisfied with the recovery progress and final results. Therefore, in the management of skin defects in the lower legs or feet that comprise less than 1.5% of the total body surface area, our surgical method is a reliable alternative to anterior or posterior thigh skin grafting.     

Optimization of ex vivo inducible nitric oxide synthase gene transfer to vein grafts.

BACKGROUND: Vein graft failure as the result of intimal hyperplasia (IH) remains a significant clinical problem. Ex vivo modification of vein grafts using gene therapy is an attractive approach to attenuate IH. Gene transfer of the inducible nitric oxide synthase (iNOS) gene effectively reduces IH. However, iNOS activity after gene transfer may be impaired by the availability of cofactor, such as tetrahydrobiopterin (BH4). The purpose of this study is to determine the optimal conditions for ex vivo adenoviral-mediated iNOS gene transfer into arterial and venous vessels. METHODS: Porcine internal jugular veins and carotid arteries were infected ex vivo with the adenoviral iNOS vector (AdiNOS) and with an adenovirus carrying the cDNA encoding guanosine triphosphate cyclohydrolase I (AdGTPCH), the rate-limiting enzyme for BH4 synthesis. The production of nitrite, cyclic guanosine monophosphate (cGMP), and biopterin were assessed daily. RESULTS: Nitric oxide (NO) production after iNOS gene transfer was maximal when vessels were cotransduced with AdGTPCH. NO production in these vessels persisted for more than 10 days. Vein segments generated approximately 2-fold more nitrite, cGMP, and biopterin than arterial segments infected with AdiNOS/AdGTPCH. Submerging vein segments into adenoviral solution resulted in improved gene transfer with greater nitrite and cGMP release compared with infections carried out under pressure intraluminally. Similarly, injury to the vein segments before infection with AdiNOS resulted in less nitrite production. CONCLUSIONS: These data demonstrate that AdiNOS can efficiently transduce vein segments ex vivo and that the cotransfer of GTPCH can optimize iNOS enzymatic activity. This cotransfer technique may be used to engineer vein grafts before coronary artery bypass to prevent IH.     

Vascular gene therapy: a reality of the 21st century

Current therapies for the treatment of atherosclerotic vascular disease are aimed at either disrupting or bypassing flow-limiting lesions. Preventative strategies are necessary to decrease the burden of disease but are limited by genetic predispositions to certain diseases and the body's innate response to injury. Gene therapy, defined as the purposeful therapeutic overexpression or attenuation of a gene product, has enormous potential benefits in vascular disease prevention and treatment strategies. This article reviews the scientific considerations involved in the development of gene therapy strategies and outlines some of the gene products that are currently being used. These interventional genetic approaches will be reviewed in the context of specific vascular disease processes, including atherosclerosis, restenosis, and thrombosis. Gene therapy will serve an enhancing and adjuvant role to evolving surgical therapies.