One-stage combined "fix and flap" approach for complex open Gustilo-Anderson IIIB lower limbs fractures: a prospective review of 102 cases.

BACKGROUND: Management of open fractures is challenging and requires a multidisciplinary team approach. This study aims to evaluate outcomes of open Gustilo-Anderson IIIB fractures managed at a single Ortho-Plastic centre following One-stage "Fix and Flap" approach. METHODS: Prospective data review for patients presenting with Gustilo-Anderson IIIB Fractures to our centre and managed with one-stage "Fix and Flap" approach. Postoperative outcomes are presented only for the patients who had a minimum of 12 months postoperative follow-up. RESULTS: 120 patients were included (83 males and 37 females). Mean age was 43 years (10-96). Tibia diaphysis was the most common site of injury (60%). 55.9% of injuries were road traffic accidents (RTA). 102 out of 120 patients had a minimum of 12 months follow-up (mean follow-up duration 25 months). Meantime from injury until definitive surgery was 7.71 days. Primary union achieved in 86.73%. Delayed union was encountered in 10.20%. 3.06% of patients had non-union. Limb salvage rate was 97.05% and Deep infection rate was only 0.98%. CONCLUSION: Our results showed that low infection rate, high limb salvage rate, and high union rate can be achieved in these complex injuries with meticulous technique, combined Ortho-Plastic (Fix and Flap) approach, and MDT input.

Sciatica Presentations and Predictors of Poor Outcomes Following Surgical Decompression of Herniated Lumbar Discs: A Review Article.

Pain associated with sciatica is one of the most common indications for surgery. The annual rate of discectomy has increased over recent years, with a significant number of patients reporting a poor outcome or symptom recurrence after surgery. This study aims to evaluate the predictors of poor outcome for patients undergoing lumbar discectomy for sciatica. A comprehensive search was conducted to find relevant literature published between 1985 and 2019. All literature with a clear methodology were included. Many factors that affect postoperative recovery after lumbar discectomy have been reported. Some evidence suggests that sociodemographic factors, including female gender, smoking, increased age, low socioeconomic status, and low education level may be associated with less favorable outcomes after surgery. Symptom duration does not appear to be associated with a significant difference in long-term outcomes; however, early surgery (within one year) may result in a faster postoperative recovery with better early results. Furthermore, patients who had discectomy for predominant leg pain had better outcomes compared to those who had the surgery for back pain as the main presentation. There was no evidence to suggest a correlation between the size of the herniated disc and long-term outcomes of sciatica; however, a higher anatomical level of herniation (L1-2, L2-3) was associated with poorer outcomes compared to the lower level of herniation (L3-4, L4-5). A few studies suggested slow postoperative recovery correlates with unemployment and depression. We recommend that the predictors of postoperative outcomes should be taken into consideration when selecting or counseling patients for lumbar disc decompression.

Management of Displaced Intra-Articular Calcaneal Fractures: A Comparative Study of Open and Minimally Invasive Surgery.

Objectives The ideal treatment of displaced intra-articular calcaneal fractures continues to be a subject of debate. The aim of the study was to compare the radiological outcome, cumulative radiation exposure, surgical time, time to surgery, wound healing times and cost involved in minimally invasive surgery (MIS) and open reduction internal fixation (ORIF) for calcaneal fractures. Methods This was a retrospective study of 39 calcaneum operated in our unit during 2012 to 2019, of which 20 had undergone ORIF and 19 had been operated upon following MIS. Results A total of 39 calcanea (37 patients) were operated, of which 20 had open procedure and 19 had MIS procedure, including one bilateral surgery in each group. Mean age of the patients in the MIS group was 42.18 years (range: 15-68 years) and that of the patients in the open group was 43 years (range: 21-75 years). Of the fractures, 53.84% (n = 21) was Sanders type III, 28.20% (n = 11) was type II and 17.94% (n = 7) was type IV. There was no statistically significant difference in the mean correction of Bohler's angle and Gissane's angle between the groups. The mean cost for implant used for each open procedure was £882.79, and the implant cost for each MIS procedure was £142.89. Mean utilisation of cumulative X-ray dose was significantly higher in MIS (0.764 mGy) in comparison to open surgery (0.392 mGy). The average surgical time for MIS was 64.9 minutes and that of open surgery was 106.3 minutes. Average waiting time for MIS was 6.6 days and that for ORIF was 9.8 days. Wound healing was quicker (average 13.4 days) in MIS than ORIF (average 17.2 days). All these differences were statistically significant. Conclusions Minimally invasive calcaneal fracture surgery is quicker and cheaper and can be performed earlier. It is associated with early wound healing, although it requires higher cumulative radiation dose.

Protective and therapeutic potential of ginger (Zingiber officinale) extract and [6]-gingerol in cancer: A comprehensive review.

Natural dietary agents have attracted considerable attention due to their role in promoting health and reducing the risk of diseases including cancer. Ginger, one of the most ancient known spices, contains bioactive compounds with several health benefits. [6]-Gingerol constitutes the most pharmacologically active among such compounds. The aim of the present work was to review the literature pertaining to the use of ginger extract and [6]-gingerol against tumorigenic and oxidative and inflammatory processes associated with cancer, along with the underlying mechanisms of action involved in signaling pathways. This will shed some light on the protective or therapeutic role of ginger derivatives in oxidative and inflammatory regulations during metabolic disturbance and on the antiproliferative and anticancer properties. Data collected from experimental (in vitro or in vivo) and clinical studies discussed in this review indicate that ginger extract and [6]-gingerol exert their action through important mediators and pathways of cell signaling, including Bax/Bcl2, p38/MAPK, Nrf2, p65/NF-κB, TNF-α, ERK1/2, SAPK/JNK, ROS/NF-κB/COX-2, caspases-3, -9, and p53. This suggests that ginger derivatives, in the form of an extract or isolated compounds, exhibit relevant antiproliferative, antitumor, invasive, and anti-inflammatory activities.

Anti-VEGF treatment in neovascular age-related macular degeneration: a treat-and-extend protocol over 2 years.

PURPOSE: To evaluate 2-year visual acuity outcome of a treat-and-extend protocol of anti-vascular endothelial growth factor treatment in age-related macular degeneration. METHODS: In this prospective cohort study, 120 age-related macular degeneration patients with choroidal neovascularization received 3 initial monthly ranibizumab or bevacizumab injections; monthly injections were continued until there was no choroidal neovascularization activity (subretinal/intraretinal fluid, loss of >5 letters, or persistent/recurrent retinal hemorrhage). When there was no choroidal neovascularization activity, the interval to the next visit/injection was extended by 2 weeks to a maximum of 12 weeks. In the presence of choroidal neovascularization activity, this interval was shortened by 2 weeks. Main outcome measures included the percentage losing <15 letters and the mean visual acuity change after 12 months and 24 months. RESULTS: Mean baseline visual acuity was 51.2 ± 12.1 Early Treatment Diabetic Retinopathy Study scores. Mean visual acuity change from baseline was +9.5 ± 10.9 and +8.0 ± 12.9 letters after 12 months and 24 months, respectively, with, on average, 8.6 ± 1.1 visits/injections in the first year and 5.6 ± 2.0 in the second year. After 12 months and 24 months, 97.5% and 95.0% of patients, respectively, lost <15 letters. CONCLUSION: The "inject-and-extend" protocol-with fewer injections and visits-delivered outcomes comparable to those of the pivotal clinical trials of monthly ranibizumab.

Genetic influences on the outcome of anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration.

PURPOSE: To determine the association of genetic variants in known age-related macular degeneration (AMD) risk-associated genes with outcome of anti-vascular endothelial growth factor (VEGF) treatment in neovascular AMD. DESIGN: Prospective cohort study. PARTICIPANTS: We enrolled 224 consecutive patients with neovascular AMD at the Royal Victorian Eye and Ear Hospital, Australia. METHODS: Patients were treated with 3 initial monthly ranibizumab or bevacizumab injections followed by 9 months of "as required" injections based on clinician's decision at each follow-up visit according to retreatment criteria. Seventeen single nucleotide polymorphisms (SNPs) in known AMD risk-associated genes including CFH (rs800292, rs3766404, rs1061170, rs2274700 and rs393955), HTRA1 (rs11200638), CFHR1-5 (rs10922153, rs16840639, rs6667243, and rs1853883), LOC387715/ARMS2 (rs3793917 and rs10490924), C3 (rs2230199 and rs1047286), C2 (rs547154), CFB (rs641153) and F13B (rs6003) were examined. Multivariate analysis was used to determine the role of each SNP in treatment outcome. MAIN OUTCOME MEASURES: The influence of selected SNPs on mean change in visual acuity (VA) at 12 months. RESULTS: Mean baseline VA was 51 ± 16.8 Early Treatment Diabetic Retinopathy Study letters. Overall, the mean change in VA from baseline was +3.2 ± 14.9 letters at 12 months. The AA (homozygote risk) genotype at rs11200638 - HTRA1 promoter SNP (P = 0.001) and GG (homozygote risk) genotype at rs10490924 (A69S) in LOC387715/ARMS2 (P = 0.002) were each significantly associated with poorer VA outcome at 12 months after multiple correction. Mean ± standard deviation change in VA from baseline in patients with AA genotype at rs11200638 was -2.9 ± 15.2 letters after 12 months compared with +5.1 ± 14.1 letters in patients with AG or GG genotypes at this SNP. Patients with either of these genotypes were also significantly more likely to lose >15 letters after 12 months. SNPs rs11200638 and rs10490924 were in high linkage disequilibrium (r(2) = 0.92). None of the other examined SNPs was associated with outcome. CONCLUSIONS: The HTRA1 promoter SNP (rs11200638) and A69S at LOC387715/ARMS2 were associated with a poorer visual outcome for ranibizumab or bevacizumab treatment in neovascular AMD, suggesting strong pharmacogenetic associations with anti-VEGF treatment. This finding could aid in applying more individualized treatment regimens based on patients' genotype to achieve optimal treatment response in AMD. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Molecular changes from dysplastic nodule to hepatocellular carcinoma through gene expression profiling.

Progression of hepatocellular carcinoma (HCC) is a stepwise process that proceeds from pre-neoplastic lesions--including low-grade dysplastic nodules (LGDNs) and high-grade dysplastic nodules (HGDNs)--to advanced HCC. The molecular changes associated with this progression are unclear, however, and the morphological cues thought to distinguish pre-neoplastic lesions from well-differentiated HCC are not universally accepted. To understand the multistep process of hepato-carcinogenesis at the molecular level, we used oligo-nucleotide microarrays to investigate the transcription profiles of 50 hepatocellular nodular lesions ranging from LGDNs to primary HCC (Edmondson grades 1-3). We demonstrated that gene expression profiles can discriminate not only between dysplastic nodules and overt carcinoma but also between different histological grades of HCC via unsupervised hierarchical clustering with 10,376 genes. We identified 3,084 grade-associated genes, correlated with tumor progression, using one-way ANOVA and a one-versus-all unpooled t test. Functional assignment of these genes revealed discrete expression clusters representing grade-dependent biological properties of HCC. Using both diagonal linear discriminant analysis and support vector machines, we identified 240 genes that could accurately classify tumors according to histological grade, especially when attempting to discriminate LGDNs, HGDNs, and grade 1 HCC. In conclusion, a clear molecular demarcation between dysplastic nodules and overt HCC exists. The progression from grade 1 through grade 3 HCC is associated with changes in gene expression consistent with plausible functional consequences.

Identification of discriminators of hepatoma by gene expression profiling using a minimal dataset approach.

The severity of hepatocellular carcinoma (HCC) and the lack of good diagnostic markers and treatment strategies have rendered the disease a major challenge. Previous microarray analyses of HCC were restricted to the selected tissue sample sets without validation on an independent series of tissue samples. We describe an approach to the identification of a composite discriminator cassette by intersecting different microarray datasets. We studied the global transcriptional profiles of matched HCC tumor and nontumor liver samples from 37 patients using cDNA (cDNA) microarrays. Application of nonparametric Wilcoxon statistical analyses (P < 1 x 10(-6)) and the criteria of 1.5-fold differential gene expression change resulted in the identification of 218 genes, including BMI-1, ERBB3, and those involved in the ubiquitin-proteasome pathway. Elevated ERBB2 and epidermal growth factor receptor (EGFR) expression levels were detected in ERBB3-expressing tumors, suggesting the presence of ERBB3 cognate partners. Comparison of our dataset with an earlier study of approximately 150 tissue sets identified multiple overlapping discriminator markers, suggesting good concordance of data despite differences in patient populations and technology platforms. These overlapping discriminator markers could distinguish HCC tumor from nontumor liver samples with reasonable precision and the features were unlikely to appear by chance, as measured by Monte Carlo simulations. More significantly, validation of the discriminator cassettes on an independent set of 58 liver biopsy specimens yielded greater than 93% prediction accuracy. In conclusion, these data indicate the robustness of expression profiling in marker discovery using limited patient tissue specimens as well as identify novel genes that are highly likely to be excellent markers for HCC diagnosis and treatment.