The role of thorax imaging in staging head and neck squamous cell carcinoma

The overall survival rate for patients with head neck squamous cell carcinoma remains disappointingly static despite improved locoregional control. This has been attributed to the development of distant metastases and second primary malignancies in these patients, a large proportion of which occur in the thorax. We retrospectively analysed the incidence of thoracic malignancies in 138 patients presenting with newly diagnosed (n = 107) or recurrent (n = 31) cancer of the head and neck over a 4-year period. All 138 patients had undergone both computerised tomography of the thorax (CT) and conventional chest radiography within one month of presenting with biopsy proven squamous cell carcinoma. Seventeen percent of these were found to have simultaneous thoracic malignancies. CT thorax was more sensitive in detecting simultaneous thoracic malignancies compared with standard chest X-ray (24/138 versus 9/138, odds ratio of 3:1 in favour of CT). All thoracic malignancies detected by chest X-ray were also detected by CT thorax. Patients presenting with recurrent tumors were significantly more likely to have simultaneous thoracic malignancies than those with newly diagnosed cancer (11/31 versus 13/107, chi2 test with Yates correction, chi2 = 4.66, p = 0.03). The primary site (laryngeal, oral or pharyngeal) or presence of nodal disease did not have an effect on the incidence of simultaneous thoracic malignancies. The presence of distant metastases and second primary malignancies has major implications in the management and prognosis of patients presenting with head and neck squamous cell carcinoma, with a large proportion of such patients succumbing to their disease within one year of diagnosis. As CT scanning of the thorax was a more effective screening investigation than standard chest X-ray in the detection of simultaneous thoracic malignancy, we recommend it for use in the staging of patients presenting with cancer of the head and neck.     

Poor performance of the modified early warning score for predicting mortality in critically ill patients presenting to an emergency department

BACKGROUND:

This study was undertaken to validate the use of the modified early warning score (MEWS) as a predictor of patient mortality and intensive care unit (ICU)/ high dependency (HD) admission in an Asian population.

METHODS:

The MEWS was applied to a retrospective cohort of 1 024 critically ill patients presenting to a large Asian tertiary emergency department (ED) between November 2006 and December 2007. Individual MEWS was calculated based on vital signs parameters on arrival at ED. Outcomes of mortality and ICU/HD admission were obtained from hospital records. The ability of the composite MEWS and its individual components to predict mortality within 30 days from ED visit was assessed. Sensitivity, specificity, positive and negative predictive values were derived and compared with values from other cohorts. A MEWS of !4 was chosen as the cut-off value for poor prognosis based on previous studies.

RESULTS:

A total of 311 (30.4%) critically ill patients were presented with a MEWS !4. Their mean age was 61.4 years (SD 18.1) with a male to female ratio of 1.10. Of the 311 patients, 53 (17%) died within 30 days, 64 (20.6%) were admitted to ICU and 86 (27.7%) were admitted to HD. The area under the receiver operating characteristic curve was 0.71 with a sensitivity of 53.0% and a specificity of 72.1% in addition to a positive predictive value (PPV) of 17.0% and a negative predictive value (NPV) of 93.4% (MEWS cut-off of !4) for predicting mortality.

CONCLUSION:

The composite MEWS did not perform well in predicting poor patient outcomes for critically ill patients presenting to an ED.KEY WORDS: Modified early warning score, Emergency department, Outcomes, Triage     

Comparing lignocaine-adrenaline-tetracaine gel with lignocaine infiltration for anesthesia during repair of lacerations: A randomized trial

BACKGROUND:

This study aimed to compare the topical anesthetic lignocaine, adrenaline, and tetracaine (LAT) (4% lignocaine, 1:2 000 adrenaline, 1% tetracaine) with the conventional lignocaine infiltration(LI) for repair of minor lacerations, for the comfort of anesthetic administration, efficacy, adverse effects and cost.

METHODS:

This was a prospective randomized clinical trial. Forty Asian patients who required toilet and suture for minor lacerations in the emergency department of the Singapore General Hospital over a 4-month period. The patients were assigned randomly to 2 arms of treatment. The first was the LAT gel group who had LAT gel applied to the laceration prior to suturing. The second was the control group in whom the anesthetic administered was lignocaine infiltration (LI) via a syringe. The pain of the process of administering anesthetic and efficacy of anesthesia were scored using the visual pain scale included within. The efficacy of LAT vs. lignocaine infiltration as an anesthetic prior to the toilet and suture of minor lacerations and complications of therapy.

RESULTS:

Twenty patients were randomized to LAT gel and 16 to LI on an intention to treat analysis. The mean pain score by patients in the LAT gel group was 2.5 (0.52 SE), and 2.5 (0.58 SE) in the LI group. The pain score for pain during application of the anesthetic was 1.5 (0.40) in the LAT gel group, and 3.5 (0.46) in the LI group. There was no difference in complications between the LAT and LI groups

CONCLUSION:

LAT gel prior to the toilet and suture of minor lacerations is proven to be as efficacious as LI in terms of patient comfort and effectiveness of anesthesia. The complications are also comparable to those treated with LI.KEY WORDS: Lignocaine infiltration, Lacerations, Emergency department, Pain score     

The role of stem cell factor and c‐KIT in keloid pathogenesis: do tyrosine kinase inhibitors have a potential therapeutic role?

Background Keloids are fibroproliferative disorders characterized by increased deposition of extracellular matrix components. Stem cell factor (SCF) and its receptor c‐KIT are expressed in a wide variety of cells and have also been demonstrated to be important modulators of the wound healing process. Objectives To examine the role of the SCF/c‐KIT system in keloid pathogenesis. Methods Immunohistochemical staining and Western blot analyses were used to examine localization and expression of SCF and c‐KIT in keloid and normal skin tissue. This was followed by the detection of SCF and c‐KIT expression in fibroblasts cultured in vitro and fibroblasts exposed to serum. To investigate the effect of epithelial–mesenchymal interactions, a two‐chamber system was employed in which keratinocytes on membrane inserts were cocultured with the fibroblasts. SCF and c‐KIT expression levels in all cell extracts and conditioned media were assayed by Western blotting. In another set of experiments, the effect of imatinib (Glivec^®, Gleevec^®; Novartis Pharma AG, Basel, Switzerland) on keloid fibroblasts was examined. Results SCF and c‐KIT were upregulated in keloid scar tissue and in cultured fibroblasts stimulated with serum, highlighting their importance in the initial phase of wound healing. We further demonstrated that epithelial–mesenchymal interactions, mimicked by coculture of keratinocytes and fibroblasts in vitro, not only stimulated secretion of the soluble form of SCF in keloid cocultures but also brought about shedding of the extracellular domain of c‐KIT perhaps by upregulation of tumour necrosis factor‐α converting enzyme which was also upregulated in keloid scars in vivo and keloid cocultures in vitro. In addition keloid cocultures expressed increased levels of phosphorylated c‐KIT highlighting an activation of the SCF/c‐KIT system. Finally, we demonstrated that imatinib, a tyrosine kinase inhibitor, may be a possible therapeutic agent for keloids. Conclusion These data indicate that the SCF/c‐KIT system plays an important role in scar pathogenesis, and underscore the role of imatinib as a key therapeutic agent in keloid scars.     

Parental psychopathology and migraine headaches among adolescent girls

Migraine headaches and depression often co-occur within individuals, and both syndromes run in families. However, knowledge about how these disorders relate across generations, as well as how migraine relates to other forms of psychopathology, is sparse. This study examined risk for migraine among female adolescent offspring of parents with different types of psychopathology. The sample was drawn from the Minnesota Twin Family Study, a community-based study of adolescents and their families ( n  = 674, 17-year-old female adolescents and their biological parents). Diagnoses of maternal, paternal and offspring major depression, antisocial behaviour, alcohol dependence and drug dependence were based on structured interviews. Migraine headaches in each family member were assessed via interviews with the mother. Parental depression, antisocial behaviour and drug dependence were associated with offspring migraine. These associations mostly remained significant even when parental migraine and the corresponding type of psychopathology in offspring were adjusted for. In contrast, there were no significant associations between parental psychopathology and offspring stomach problems, indicating that these associations did not extend to all offspring somatic symptoms. These results emphasize the need to look at antisocial behaviour and substance-related problems when examining associations between migraine and psychopathology, and indicate that more research on inter-generational links between migraine and psychopathology is needed.     

Inherent stochasticity during insulator–metal transition in VO2

Vanadium dioxide (VO₂), which exhibits a near-room-temperature insulator–metal transition, has great potential in applications of neuromorphic computing devices. Although its volatile switching property, which could emulate neuron spiking, has been studied widely, nanoscale studies of the structural stochasticity across the phase transition are still lacking. In this study, using in situ transmission electron microscopy and ex situ resistive switching measurement, we successfully characterized the structural phase transition between monoclinic and rutile VO₂ at local areas in planar VO₂/TiO₂ device configuration under external biasing. After each resistive switching, different VO₂ monoclinic crystal orientations are observed, forming different equilibrium states. We have evaluated a statistical cycle-to-cycle variation, demonstrated a stochastic nature of the volatile resistive switching, and presented an approach to study in-plane structural anisotropy. Our microscopic studies move a big step forward toward understanding the volatile switching mechanisms and the related applications of VO₂ as the key material of neuromorphic computing.

Resistive switching in vanadium oxides has attracted much attention because of the potential applications in bioinspired neuromorphic computing and nonvolatile memories (1–4). In a basic neural network, neurons can generate nonlinear electric spikes under external excitations, while the synapses allow for the modulation of interconnected weights between neurons. In most hardware-based neuromorphic approaches, volatile switching devices (threshold switching) were used to emulate the artificial spiking neuronal behaviors, while nonvolatile switching memories were often used to mimic the synaptic functionalities (1). VO₂, whose insulator–metal transition (IMT) is above room temperature (T_IMT ∼340 K) (5), has been widely studied as a neuristor (6). It is considered a promising candidate for energy-efficient neurons due to its threshold spiking phenomenon. In pristine VO₂ it is believed that the resistive switching can be triggered by local Joule heating across the IMT, while nonthermal switching can be induced using defect engineering (7). Recently, both volatile and nonvolatile functionalities have been achieved in VO₂ based on different switching mechanisms (8). In previous work, in situ X-ray nanomapping was used to track the out-of-plane monoclinic and rutile Bragg peaks during resistive switching (9). However, up to now the nanoscale in-plane structural anisotropy and its intrinsic stochasticity have been rarely explored (10, 11): How the system returns from metallic state to insulating state and how the structural transition influences the switching. In addition, the control of the switching usually appears to be imprecise, i.e., the voltage necessary to initiate the phase transition is not a constant (even within a single grain) (12). Therefore, it is of critical importance to understand the stochastic behavior within the neuron device and the phase transition mechanism at nanoscale under external stimuli, since the switching has to be done a large number of times during the neuron firing process. In addition, the IMT of VO₂ nanodevices can show multiple jumps, which implies that the domain structures in VO₂ may influence the transition behavior (13). Also, many physical properties, such as electrical, magnetic, and optical properties, show significant changes during the IMT process (14–16).Here, we use in situ biasing transmission electron microscopy (TEM) with ex situ electrical transport measurement to characterize the structural phase transition across the volatile switching in VO₂. In-plane resistive switching was studied in epitaxial VO₂/TiO₂ (001) nanodevices. The original in-plane structural isotropy in the VO₂ rutile structure (R phase) will lead to anisotropy in the monoclinic phase (M1 phase) after resistive switching. Multiple monoclinic domains will form when the system returns to the insulating state. The IMT phase transition and the simultaneous electrical properties change have been systematically studied. Our results demonstrate that the structural anisotropy between different M1 VO₂ domains plays an important role in the insulating state. In addition, this study provides a thorough understanding of the volatile resistive switching process and shows that the intrinsic variability is a key issue in developing stochastic neuromorphic networks.