Advancing Use of DEXA Scans to Quantitatively and Qualitatively Evaluate Lateral Spinal Curves, for Preliminary Identification of Adolescent Idiopathic Scoliosis.

Dual-energy X-ray absorptiometry (DEXA) scan is an emerging screening method for identifying likely adolescent idiopathic scoliosis (AIS). Using DEXA in an unbiased population sample (the Raine Study), we aimed to report the inter-rater reliability and minimal detectable change (MDC95) for scoliosis curve angle measurement, identify likely AIS prevalence, and the concordance between reported AIS diagnosis and DEXA-identified likely AIS. Scoliosis curve angles were measured using the modified Ferguson method on DEXA scans (n = 1238) at age 20 years. For curve angle inter-rater reliability, two examiners measured angles (6-40°) on 41 scans. Likely, AIS was determined with quantitative and qualitative criteria (modified Ferguson angles ≥ 10° and expert review of spinal curves).The inter-rater reliability for scoliosis curve angle measurement was good-excellent (ICC: 0.82; 95% CI: 0.71-0.89; p < 0.001), and MDC95 was 6.2°. The prevalence of likely AIS was 2.1% (26/1238). Diagnosis of AIS was reported despite little or no scoliosis curve (< 3.8°) for 20 participants (1.6%), and diagnosis of AIS was not reported despite scoliosis curve ≥ 10° for 11 participants (0.9%). Results support the use of modified Ferguson method to measure scoliosis curve angles on DEXA. There is potential utility for using a combination of quantitative measurement and qualitative criteria to evaluate DEXA images, to identify likely AIS for reporting prevalence. Without formal school screening, the analysis of DEXA in this population sample suggested that relying on current health professional diagnosis alone could result in 2.5% of this cohort being at risk of false positive diagnosis or delay in necessary management due to non-diagnosis of AIS.

Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China.

BACKGROUND: Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown. PATIENTS AND METHODS: A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City. RESULTS: Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49). CONCLUSION: IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis. CLINICAL TRIAL NUMBER: NCT00941538.

Manchester - Fothergill procedure for treatment of recurrence procidentia in young nulliparous woman: A case report.

Procidentia is uncommon condition altering quality of life of young and nulliparous women. Its management poses significant dilemma and challenges as its associated body image, fertility and sexuality issues. Uterine preservation surgery described by Archibald Donald in 1888 known as Manchester -Fothergill procedure seems best option as alternative to vaginal hysterectomy. Despite its increasing popularity among surgeons and patients, robust clinical evidence is needed. We report a case of recurrent procidentia in a young nulliparous woman who had Manchester repair following vaginal sacrospinous hysteropexy. We concluded that Manchester repair is a useful and safe alternative for uterine-preserving technique.

The association of postoperative pulmonary complications in 109,360 patients with pressure-controlled or volume-controlled ventilation.

We thought that the rate of postoperative pulmonary complications might be higher after pressure-controlled ventilation than after volume-controlled ventilation. We analysed peri-operative data recorded for 109,360 adults, whose lungs were mechanically ventilated during surgery at three hospitals in Massachusetts, USA. We used multivariable regression and propensity score matching. Postoperative pulmonary complications were more common after pressure-controlled ventilation, odds ratio (95%CI) 1.29 (1.21-1.37), p < 0.001. Tidal volumes and driving pressures were more varied with pressure-controlled ventilation compared with volume-controlled ventilation: mean (SD) variance from the median 1.61 (1.36) ml.kg-1 vs. 1.23 (1.11) ml.kg-1 , p < 0.001; and 3.91 (3.47) cmH2 O vs. 3.40 (2.69) cmH2 O, p < 0.001. The odds ratio (95%CI) of pulmonary complications after pressure-controlled ventilation compared with volume-controlled ventilation at positive end-expiratory pressures < 5 cmH2 O was 1.40 (1.26-1.55) and 1.20 (1.11-1.31) when ≥ 5 cmH2 O, both p < 0.001, a relative risk ratio of 1.17 (1.03-1.33), p = 0.023. The odds ratio (95%CI) of pulmonary complications after pressure-controlled ventilation compared with volume-controlled ventilation at driving pressures of < 19 cmH2 O was 1.37 (1.27-1.48), p < 0.001, and 1.16 (1.04-1.30) when ≥ 19 cmH2 O, p = 0.011, a relative risk ratio of 1.18 (1.07-1.30), p = 0.016. Our data support volume-controlled ventilation during surgery, particularly for patients more likely to suffer postoperative pulmonary complications.

Artificial Neural Networks in Image Processing for Early Detection of Breast Cancer.

Medical imaging techniques have widely been in use in the diagnosis and detection of breast cancer. The drawback of applying these techniques is the large time consumption in the manual diagnosis of each image pattern by a professional radiologist. Automated classifiers could substantially upgrade the diagnosis process, in terms of both accuracy and time requirement by distinguishing benign and malignant patterns automatically. Neural network (NN) plays an important role in this respect, especially in the application of breast cancer detection. Despite the large number of publications that describe the utilization of NN in various medical techniques, only a few reviews are available that guide the development of these algorithms to enhance the detection techniques with respect to specificity and sensitivity. The purpose of this review is to analyze the contents of recently published literature with special attention to techniques and states of the art of NN in medical imaging. We discuss the usage of NN in four different medical imaging applications to show that NN is not restricted to few areas of medicine. Types of NN used, along with the various types of feeding data, have been reviewed. We also address hybrid NN adaptation in breast cancer detection.

Long-term, high-level hepatic secretion of acid α-glucosidase for Pompe disease achieved in non-human primates using helper-dependent adenovirus.

Pompe disease (glycogen storage disease type II (GSD-II)) is a myopathy caused by a genetic deficiency of acid α-glucosidase (GAA) leading to lysosomal glycogen accumulation causing muscle weakness, respiratory insufficiency and death. We previously demonstrated in GSD-II mice that a single injection of a helper-dependent adenovirus (HD-Ad) expressing GAA resulted in at least 300 days of liver secretion of GAA, correction of the glycogen storage in cardiac and skeletal muscles and improved muscle strength. Recent reports suggest that gene therapy modeling for lysososomal storage diseases in mice fails to predict outcomes in larger animal models. We therefore evaluated an HD-Ad expressing GAA in non-human primates. The baboons not only tolerated the procedure well, but the results also confirmed that a single dose of the HD-Ad allowed the livers of the treated animals to express and secrete large amounts of GAA for at least 6 months, at levels similar to those achieved in mice. Moreover, we detected liver-derived GAA in the heart, diaphragm and skeletal muscles of the treated animals for the duration of the study at levels that corrected glycogen accumulation in mice. This work validates our proof-of-concept studies in mice, and justifies future efforts using Ad-based vectors in Pompe disease patients.

Identification of germline alterations in breast cancer predisposition genes among Malaysian breast cancer patients using panel testing.

Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.

Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study.

OBJECTIVE: To estimate the accuracy of transvaginal ultrasound (TVS) measurement of endometrial thickness (ET) in diagnosing endometrial cancer in postmenopausal women with vaginal bleeding (PMB). DESIGN: Retrospective cohort study. SETTING: One-stop PMB clinic in a Hong Kong teaching hospital. POPULATION: A cohort of 4383 women with PMB. METHODS: Transvaginal ultrasonic measurement of ET and endometrial biopsies were obtained in women presenting with PMB between 2002 and 2013. Endometrial histology was used as the reference standard to calculate accuracy estimates. MAIN OUTCOME MEASURES: Accuracy data for TVS ET presented as sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve. RESULTS: Endometrial cancer was diagnosed in 3.8% of women. The median ET in those with endometrial cancer was significantly higher than those with benign conditions (15.7 versus 3.2 mm, P < 0.001). The area under the ROC curve was 0.92 (95% CI 0.89-0.94). The sensitivity for the detection of endometrial cancer at 3-, 4-, and 5-mm cut-offs were 97.0% (95% CI 94.5-99.6%), 94.1% (95% CI 90.5-97.6%), and 93.5% (95% CI 89.7-97.2%), respectively. The corresponding estimates of specificity at these thresholds were 45.3% (95% CI 43.8-46.8%), 66.8% (65.4-68.2%), and 74.0% (72.7-75.4%). CONCLUSIONS: Transvaginal ultrasound using a 3-mm cut-off has high sensitivity for detecting endometrial cancer and can identify women with PMB who are highly unlikely to have endometrial cancer, thereby avoiding more invasive endometrial biopsy.

Length of stay an important mediator of hospital-acquired methicillin-resistant Staphylococcus aureus.

Hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) is becoming increasingly established in Asian hospitals. The primary aim of this study was to decompose the risk factors for HA-MRSA based on conceptual clinical pathways. The secondary aim was to show the amount of effect attributable to antibiotic exposure and total length of stay before outcome (LBO) so that institutions can manage at-risk patients accordingly. A case-control study consisting of 1200 inpatients was conducted in a large tertiary hospital in Singapore between January and December 2006. Results from the generalized structural equation model (GSEM) show that LBO [adjusted odds ratio (aOR) 14·9, 95% confidence interval (CI) 8·7-25·5], prior hospitalization (aOR 6·2, 95% CI 3·3-11·5), and cumulative antibiotic exposure (aOR 3·5, 95% CI 2·3-5·3), directly affected HA-MRSA acquisition. LBO accounted for the majority of the effects due to age (100%), immunosuppression (67%), and surgery (96%), and to a lesser extent for male gender (22%). Our model enabled us to account and quantify effects of intermediaries. LBO was found to be an important mediator of age, immunosuppression and surgery on MRSA infection. Traditional regression approaches will not only give different conclusions but also underestimate the effects. Hospitals should minimize the hospital stay when possible to reduce the risk of MRSA.

Treatment of bone disorders with parathyroid hormone: success and pitfalls.

Bone diseases such as osteoporosis, osteoarthritis, bone tumours and bone fractures are rather common and not just in the elderly. Parathyroid hormone (PTH) is responsible for maintaining calcium homeostasis, increasing bone mineral density (BMD), increasing cortical and trabecular bone thickness and thus increasing bone strength. Teriparatide (PTH 1-34) has the same effects as endogenous PTH and is pharmacologically used to treat bone diseases such as osteoporosis, osteoarthritis, bone fractures and bone tumours. This review discusses how PTH 1-34 plays a role in managing bone diseases. Clinical studies have shown that short or intermittent dosing of PTH 1-34 has minimal adverse effects, while long-term dosing (over two years) has been linked to de novo osteoarthritis and bone deformation. Currently PTH therapy is only approved in the treatment of post-menopausal osteoporosis, however it is also proven to have effects in treating osteoarthritis, bone tumours and bone fractures. If the patient undergoing therapy is closely monitored, the major pitfalls are very unlikely to take place, thus it is highly recommended that patients be closely monitored by a medical practitioner.

A cautionary tale; squamous cell carcinoma of the gingiva.

BACKGROUND AND OBJECTIVES: Oral squamous cell carcinoma is characterised by varied clinical manifestations and is often diagnosed at an advanced stage. This article highlights a case of gingival squamous cell carcinoma which was initially diagnosed and treated as localised periodontitis. METHODS: A 64-year-old Caucasian male had a 2-year history of discomfort and swelling around his upper anterior teeth. His dentist diagnosed localised periodontitis around tooth 11. The patient was treated with regular scaling but showed no improvement. Teeth 11 and 21 were subsequently extracted. He returned later with a swelling in his anterior maxilla and was referred to the Whangarei Hospital Dental Department. RESULTS: The histopathological report confirmed a diagnosis of squamous cell carcinoma. The patient was referred to Auckland for treatment and underwent a tracheostomy, maxillectomy, bilateral selective neck dissection and fibula free flap reconstruction. All lymph nodes retrieved and margins of the lesion were clear, and the patient did not require radiotherapy. He will be monitored over the next 5 years for recurrence. CONCLUSIONS: Gingival squamous cell carcinoma can be easily misdiagnosed. Suspicious lesions which are non-responsive to conventional therapy should be biopsied, even if they are not in the classic high risk anatomical areas of the oral cavity.

Retinal transduction profiles by high-capacity viral vectors.

Retinal gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. However, the limited cargo capacity of AAV prevents their use for therapy of those inherited retinopathies (IRs) due to mutations in large (>5 kb) genes. Viral vectors derived from adenovirus (Ad), lentivirus (LV) and herpes virus (HV) can package large DNA sequences, but do not target efficiently retinal photoreceptors (PRs) where the majority of genes responsible for IRs are expressed. Here, we have evaluated the mouse retinal transduction profiles of vectors derived from 16 different Ad serotypes, 7 LV pseudotypes and from a bovine HV. Most of the vectors tested transduced efficiently the retinal pigment epithelium. We found that LV-GP64 tends to transduce more PRs than the canonical LV-VSVG, albeit this was restricted to a narrow region. We observed more extensive PR transduction with HdAd1, 2 and 5/F35++ than with LV, although none of them outperformed the canonical HdAd5 or matched the extension of PR transduction achieved with AAV2/8.

Practical application of using local anaesthetics: surgical perspectives.

With reduction in surgical training, surgical trainees may find it difficult deal with local anaesthetic agents because of lack of exposure and knowledge. We have summarised the common usage of local anaesthetics in various situation. The trainees need to gain competence by understanding the basics and practising them under supervision.

Response of Coptotermes curvignathus (Isoptera: Rhinotermitidae) to formaldehyde catcher-treated particleboard.

The objective of this study is to investigate the feasibility of formaldehyde catcher as termites repellent. Single-layered UF-bonded particleboard was post-treated with formaldehyde catcher and heat respectively. Besides that, some boards were also produced with the formaldehyde catcher was added into the resin during the blending process, called add-in method. Particleboard post-treated with formaldehyde catcher reported the most severe attack. Heat-treated particleboard showed slightly better durability than the control blocks while the add-in catcher showed the best durability among three methods. A valid test was obtained as the termites survived the first week of the test. However, all the termites were found dead at the end of the test.

Spirometric reference standards for preschool children in Hong Kong.

1. Prediction equations and normograms are established using incentive spirometry in a community cohort of 770 Hong Kong Chinese children aged 2 to 6 years. 2. All spirometric parameters depend mainly on standing height. Boys have higher values than girls. 3. Forced expiratory volumes depend on birth weight, place of birth, history of wheezing, and environmental tobacco smoke (ETS) exposure. 4. High urinary cotinine level as a biomarker of ETS exposure is noted in about one tenth of the children. 5. Urinary cotinine level is inversely associated with all spirometric parameters. This supports implementation of the smoking cessation programme.

AKT induces senescence in human cells via mTORC1 and p53 in the absence of DNA damage: implications for targeting mTOR during malignancy.

The phosphatidylinositol 3-kinase (PI3K)/AKT and RAS oncogenic signalling modules are frequently mutated in sporadic human cancer. Although each of these pathways has been shown to play critical roles in driving tumour growth and proliferation, their activation in normal human cells can also promote cell senescence. Although the mechanisms mediating RAS-induced senescence have been well characterised, those controlling PI3K/AKT-induced senescence are poorly understood. Here we show that PI3K/AKT pathway activation in response to phosphatase and tensin homolog (PTEN) knockdown, mutant PI3K, catalytic, α polypeptide (PIK3CA) or activated AKT expression, promotes accumulation of p53 and p21, increases cell size and induces senescence-associated ß-galactosidase activity. We demonstrate that AKT-induced senescence is p53-dependent and is characterised by mTORC1-dependent regulation of p53 translation and stabilisation of p53 protein following nucleolar localisation and inactivation of MDM2. The underlying mechanisms of RAS and AKT-induced senescence appear to be distinct, demonstrating that different mediators of senescence may be deregulated during transformation by specific oncogenes. Unlike RAS, AKT promotes rapid proliferative arrest in the absence of a hyperproliferative phase or DNA damage, indicating that inactivation of the senescence response is critical at the early stages of PI3K/AKT-driven tumourigenesis. Furthermore, our data imply that chronic activation of AKT signalling provides selective pressure for the loss of p53 function, consistent with observations that PTEN or PIK3CA mutations are significantly associated with p53 mutation in a number of human tumour types. Importantly, the demonstration that mTORC1 is an essential mediator of AKT-induced senescence raises the possibility that targeting mTORC1 in tumours with activated PI3K/AKT signalling may exert unexpected detrimental effects due to inactivation of a senescence brake on potential cancer-initiating cells.

Simple technique of selecting the correct feeding gastrostomy button.

Feeding gastrostomy is often performed in children with neurological conditions e.g. cerebral palsy or cystic fibrosis. A feeding button is often used to replace the gastrostomy tube for convenience. The button often leaks and the correct size and length is difficult to choose. The authors describe an easy and perfect way of choosing the correct size and length button by using Foley catheters.

Laparoscopic retroperitoneal/mesenteric lymph node sampling: a safe and effective technique.

INTRODUCTION: Needle aspiration and core biopsies are commonly used to assess retroperitoneal lymph nodes. However, the tissue obtained by this method is insufficient to define and type the tumour. This article demonstrates the feasibility and safety of the laparoscopic approach in obtaining an adequate volume of lymph node tissue for typing. METHODS: Laparoscopic retroperitoneal lymph node biopsy was performed on 12 patients over a period of five years. A pneumoperitoneum was induced with a Veress needle, and an initial 10-mm trocar was inserted in the sub-umbilical region in order to carry a 30-degree telescope. Two or more 5-mm ports were inserted into the targeted areas under laparoscopic guidance to achieve optimal triangulation in order to access the nodal tissue. RESULTS: The procedure was successful in 11 out of the 12 patients. An average volume of 1.7 cm3 of tissue was harvested for each patient. In one patient with preoperatively undiagnosed portal hypertension, laparoscopy was converted to an open procedure due to bleeding. In all patients, the histology was adequate and contributed to the diagnosis, allowing rapid institution of treatment. The diagnosis was reactive lymphadenopathy in three patients and sarcoidosis in one patient. Seven others suffered from various conditions, including lymphoma, leukaemia, secondary from unknown origin and Castleman's disease. CONCLUSION: Laparoscopy allows access to perihepatic and perisplenic areas, and is a procedure of choice when needle biopsy is not possible or fails to provide an adequate sample.

Outcome of laparoscopy-assisted feeding tube insertion in elderly stroke victims.

BACKGROUND: When percutaneous endoscopic gastrostomy (PEG) is not possible, or fails, the patient is referred for laparoscopic gastrostomy or jejunostomy (LAG/J). METHOD: During 2005-2008, we performed laparoscopy-assisted feeding tube insertion on 15 patients. We assessed the outcome in terms of leaks, infection, longevity etc. The patients were followed-up for up to 12 months. RESULTS: The procedure was successful in 14/15 patients. However, thirteen died within little more than a year, of whom seven suffered from pneumonia or aspiration. DISCUSSION: Our study confirms that LAG/J is technically possible, carries a high morbidity, is a last ditch attempt and that it does not change the general prognosis of these debilitated patients.

Inhibition of c-Met downregulates TIGAR expression and reduces NADPH production leading to cell death.

c-Met represents an important emerging therapeutic target in cancer. In this study, we demonstrate the mechanism by which c-Met tyrosine kinase inhibition inhibits tumor growth in a highly invasive Asian-prevalent head and neck cancer, nasopharyngeal cancer (NPC). c-Met tyrosine kinase inhibitors (TKIs; AM7 and c-Met TKI tool compound SU11274) downregulated c-Met phosphorylation, resulting in marked inhibition of NPC cell growth and invasion. Strikingly, inhibition of c-Met resulted in significant downregulation of TP53-induced Glycolysis and Apoptosis Regulator (TIGAR) and subsequent depletion of intracellular NADPH. Importantly, overexpression of TIGAR ameliorated the effects of c-Met kinase inhibition, confirming the importance of TIGAR downregulation in the growth inhibitory activity of c-Met TKI. The effects of c-Met inhibition on TIGAR and NADPH levels were observed with two different c-Met TKIs (AM7 and SU11274) and with multiple cell lines. As NADPH provides a crucial reducing power required for cell survival and proliferation, our findings reveal a novel mechanistic action of c-Met TKI, which may represent a key effect of c-Met kinase inhibition. Our data provide the first evidence linking c-Met, TIGAR and NADPH regulation in human cancer cells suggesting that inhibition of a tyrosine kinase/TIGAR/NADPH cascade may have therapeutic applicability in human cancers.