Rabies vaccine and neuraxial anaesthesia

This case report of neuraxial anaesthesia for emergency orthopaedic surgery serves to highlight the dilemma faced by anaesthetists when surgical intervention becomes necessary in a patient on anti-rabies vaccine. The two issues of importance are the possible reduction in the efficacy of vaccination by an immunosuppressive effect of anaesthesia and surgery, and the possible need to avoid local anaesthetics for the provision of postoperative analgesia to assist in the early detection of any neurological deficit.Keywords: rabies; vaccine; anaesthesia; neuraxial bloc

A simulation tool for better management of retinal services

Background: Advances in the management of retinal diseases have been fast-paced as new treatments become available, resulting in increasing numbers of patients receiving treatment in hospital retinal services. These patients require frequent and long-term follow-up and repeated treatments, resulting in increased pressure on clinical workloads. Due to limited clinic capacity, many National Health Service (NHS) clinics are failing to maintain recommended follow-up intervals for patients receiving care. As such, clear and robust, long term retinal service models are required to assess and respond to the needs of local populations, both currently and in the future. Methods: A discrete event simulation (DES) tool was developed to facilitate the improvement of retinal services by identifying efficiencies and cost savings within the pathway of care. For a mid-size hospital in England serving a population of over 500,000, we used 36 months of patient level data in conjunction with statistical forecasting and simulation to predict the impact of making changes within the service. Results: A simulation of increased demand and a potential solution of the 'Treat and Extend' (T&E) regimen which is reported to result in better outcomes, in combination with virtual clinics which improve quality, effectiveness and productivity and thus increase capacity is presented. Without the virtual clinic, where T&E is implemented along with the current service, we notice a sharp increase in the number of follow-ups, number of Anti-VEGF injections, and utilisation of resources. In the case of combining T&E with virtual clinics, there is a negligible (almost 0%) impact on utilisation of resources. Conclusions: Expansion of services to accommodate increasing number of patients seen and treated in retinal services is feasible with service re-organisation. It is inevitable that some form of initial investment is required to implement service expansion through T&E and virtual clinics. However, modelling with DES indicates that such investment is outweighed by cost reductions in the long term as more patients receive optimal treatment and retain vision with better outcomes. The model also shows that the service will experience an average of 10% increase in surplus capacity.Peer reviewedFinal Published versio

The relationship between the insulin-like growth factor-1 axis, weight loss, an inflammation-based score and survival in patients with inoperable non-small cell lung cancer

<b>Background & aims:</b> The involvement of a systemic inflammatory response, as evidenced by the Glasgow Prognostic Score (GPS), is associated with weight loss and poor outcome in patients with non-small cell lung cancer. There is good evidence that nutritional and functional decline in patients with advanced malignant disease is associated with catabolic changes in metabolism. However, defects in anabolism may also contribute towards nutritional decline in patients with cancer. The aim of the present study was to examine the relationship between IGF-1 and IGFBP-3, performance status, mGPS and survival in patients with inoperable NSCLC. <b>Methods:</b> 56 patients with inoperable NSCLC were studied. The plasma concentrations of IGF-1, IGFBP-3 and leptin were measured using ELISA and RIA. <b>Results:</b> The patients were predominantly male (61%), over 60 years old (80%), with advanced (stage III or IV) disease (98%), with a BMI≥20 (84%), an ECOG-ps of 0 or 1 (79%), a haemoglobin (59%) and white cell count (79%) in the reference range. On follow-up 43 patients died of their cancer. On univariate analysis, BMI (p<0.05), Stage (p<0.05), ECOG-ps (p<0.05), haemoglobin (p<0.05), white cell count (p<0.05) and mGPS (p<0.05) were associated with cancer specific survival. There was no association between age, sex, treatment, IGF-1, IGFBP-3, IGF-1:IGFBP-3 ratio, or leptin and cancer specific survival. With an increasing mGPS concentrations of haemoglobin (p<0.005) and IGFBP-3 (p<0.05) decreased. mGPS was not associated with either IGF-1(p>0.20), or leptin (p>0.20). <b>Conclusions:</b> In summary, the results of this study suggest that anabolism (IGF-1 axis) does not play a significant role in the relationship between nutritional and functional decline, systemic inflammation and poor survival in patients with inoperable NSCLC

Dickkopf-related protein 1 (Dkk1) regulates the accumulation and function of myeloid derived suppressor cells in cancer

Tumor–stroma interactions contribute to tumorigenesis. Tumor cells can educate the stroma at primary and distant sites to facilitate the recruitment of heterogeneous populations of immature myeloid cells, known as myeloid-derived suppressor cells (MDSCs). MDSCs suppress T cell responses and promote tumor proliferation. One outstanding question is how the local and distant stroma modulate MDSCs during tumor progression. Down-regulation of β-catenin is critical for MDSC accumulation and immune suppressive functions in mice and humans. Here, we demonstrate that stroma-derived Dickkopf-1 (Dkk1) targets β-catenin in MDSCs, thus exerting immune suppressive effects during tumor progression. Mice bearing extraskeletal tumors show significantly elevated levels of Dkk1 in bone microenvironment relative to tumor site. Strikingly, Dkk1 neutralization decreases tumor growth and MDSC numbers by rescuing β-catenin in these cells and restores T cell recruitment at the tumor site. Recombinant Dkk1 suppresses β-catenin target genes in MDSCs from mice and humans and anti-Dkk1 loses its antitumor effects in mice lacking β-catenin in myeloid cells or after depletion of MDSCs, demonstrating that Dkk1 directly targets MDSCs. Furthermore, we find a correlation between CD15(+) myeloid cells and Dkk1 in pancreatic cancer patients. We establish a novel immunomodulatory role for Dkk1 in regulating tumor-induced immune suppression via targeting β-catenin in MDSCs

Titanium elastic nails versus spica cast in pediatric femoral shaft fractures:A systematic review and meta-analysis of 1012 patients

Background: There is a general consensus on the management of femoral fractures in children younger than two years and adolescents older than sixteen years. The best treatment for patients younger than sixteen years of age is still debatable. Titanium Elastic Nails (TEN), is widely used with some evidence, nonetheless, we undertook a systematic meta-analysis to assess the efficacy of TEN compared to Spica cast for the management of femoral shaft fracture in children aged between 2 to 16 years old. Methods: A computer literature search of PubMed, Scopus, Web of Science, CINAHL and Cochrane Central was conducted using relevant keywords. We included clinical trials and observational studies that compared TEN versus Spica cast; Records were screened for eligible studies and data were extracted and synthesized using Review Manager version 5.3 for Windows. Our search found 573 unique articles. After screening the abstract and relevant full text, 12 studies with a total of 1012 patients were suitable for the final analysis. Results: In terms terms of union (in weeks), the reported effect sizes favoured the TEN group in two included studies only. Moreover, the overall standardized mean difference in sagittal (SMD -0.48, 95% CI [-0.70 to -0.26], P<0.001) and coronal angulations (SMD -0.66, 95% CI [-1.00 to -0.31], P<0.001) favored TEN fixation in management of femoral fractures younger than 16 years. The reported length of hospital stay was not consistent across studies. The overall risk ratio of malalignment (RR=0.39, 95% CI [0.27 to 0.57], P<0.001) favored the TEN as well as walking independently. Based on our analysis, TEN treatment is superior to traction and hip spica for femoral fractures in patients younger than 16 years old. Conclusion: Based on our analysis we recommend the use of TEN fixation in management of pediatric femoral fractures in patients younger than 16 years

Case Report Open Tracheostomy after Aborted Percutaneous Approach due to Tracheoscopy Revealing Occult Tracheal Wall Ulcer

Tracheostomy is a common procedure for intensive care patients requiring prolonged mechanical ventilation. In this case report, we describe a 78-year-old female patient admitted for an aneurysm of the cerebral anterior communicating artery. Following immediate endovascular coiling, she remained ventilated and was transferred to the neurological intensive care unit. On postoperative day ten, a percutaneous tracheostomy (PCT) was requested; however, a large ulcer or possible tracheoesophageal fistula was identified on the posterior tracheal wall following bronchoscopic assessment of the trachea. Therefore, the requested PCT procedure was aborted. An open tracheostomy in the operating room was completed; however, due to the position and depth of the ulcer, a reinforced endotracheal tube (ETT) was placed via the tracheostomy. Four days later, the reinforced ETT was replaced with a Shiley distal extended tracheostomy tube to bypass the ulceration. Careful inspection and evaluation of the tracheostomy site before PCT prevented a potentially life-threatening issue in our patient

Interleukin-6 gene amplification and shortened survival in glioblastoma patients

Interleukin-6 (IL-6) is known to promote tumour growth and survival. We evaluated IL-6 gene amplification in tumours from 53 glioma patients using fluorescence in situ hybridisation. Amplification events were detected only in glioblastomas (15 out of 36 cases), the most malignant tumours, and were significantly associated with decreased patient survival

The relationship between the preoperative systemic inflammatory response and cancer-specific survival in patients undergoing potentially curative resection for renal clear cell cancer

The relationship between tumour stage, grade (Fuhrman), performance status (ECOG), a combined score (UCLA Integrated Staging System, UISS), systemic inflammatory response (elevated C-reactive protein concentration), and cancer-specific survival was examined in patients undergoing potentially curative resection for renal clear cell cancer (n=100). On univariate survival analysis, sex (P=0.050), tumour stage (P=0.001), Fuhrman grade (P<0.001), UISS (P<0.001), C-reactive protein (P=0.002) were significant predictors of survival. On multivariate analysis with sex, UISS and C-reactive protein entered as covariates, only UISS (HR 2.70, 95% CI 1.00–7.30, P=0.050) and C-reactive protein (HR 4.00, 95% CI 1.21–13.31, P=0.024) were significant independent predictors of survival. The presence of a preoperative systemic inflammatory response predicts poor cancer-specific survival in patients who have undergone potentially curative resection for renal clear cell cancer

D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL

D-type cyclins (D1, D2, and D3) are components of the mammalian core cell-cycle machinery and function to drive cell proliferation. Here, we report that D-cyclins perform a rate-limiting antiapoptotic function in vivo. We found that acute shutdown of all three D-cyclins in bone marrow of adult mice resulted in massive apoptosis of all hematopoietic cell types. We demonstrate that adult hematopoietic stem cells are particularly dependent on D-cyclins for survival and that they are especially sensitive to cyclin D loss. Surprisingly, we found that the antiapoptotic function of D-cyclins also operates in quiescent hematopoietic stem and progenitor cells. Our analyses revealed that D-cyclins repress the expression of the death receptor Fas and its ligand, FasL. Acute ablation of D-cyclins upregulated these proapoptotic genes and led to Fas- and caspase 8-dependent apoptosis. These results reveal an unexpected function of cell-cycle proteins in controlling apoptosis in normal cell homeostasis