The Characteristics of Real-time Transvaginal Sono-elastography in Endometrial Cancer.

Background: Endometrial cancer is the most common gynecological cancer among women in developed countries. Sono-elastography is an extended ultrasonographic technique that has been shown to be useful in a wide range of conditions ranging from breast, prostate, and thyroid nodules to chronic liver disease and musculoskeletal conditions. The aim of this study is to compare the sonoelastographic features of endometrial malignancy and normal endometrium. Methods: This case-control observational study was conducted at a single institution. Participants with histologically proven endometrial cancer according to the results from microcurettage or hysteroscopic biopsy and scheduled for total hysterectomy were included as cases, while asymptomatic women scheduled for routine screening ultrasound examination were recruited as controls. Both cases and controls underwent conventional B-mode transvaginal ultrasonography and strain elastography. Demographic, ultrasonographic, and histopathologic findings were analyzed. Results: A total of 29 endometrial cancer patients (cases) and 28 normal females (controls) were included in the analysis. There was no significant difference in the mean age between the two groups, but the mean body weight was significantly higher in the case group (P < 0.001). The strain ratio and elastographic thickness ratio of the endometrium were statistically significantly different between the case and the control group (P ≤ 0.05) due to increased endometrial stiffness in cancer patients as compared to the normal group. Conclusion: Our results suggest that endometrial cancer can result in increased stiffness that is detectable by transvaginal sonoelastography. Sonoelastography may serve as an adjunct to conventional ultrasound in evaluating the endometrium of women with abnormal uterine bleeding.

The Association Between Preoperative Pain Catastrophizing and Chronic Pain After Hysterectomy - Secondary Analysis of a Prospective Cohort Study.

PURPOSE: Hysterectomy is associated with a high incidence of chronic post-hysterectomy pain (CPHP). Pain catastrophizing, a negative cognitive-affective response to pain, is associated with various pain disorders but its role in CPHP is unclear. We aimed to determine the association of high preoperative pain catastrophizing with CPHP development and functional impairment 4 months after surgery. PATIENTS AND METHODS: Secondary analysis of a prospective cohort study of women undergoing abdominal/laparoscopic hysterectomy to investigate the association between high pain catastrophizing (pain catastrophizing scale, PCS≥20) with CPHP and associated functional impairment (defined as impairment with standing for ≥30 minutes, sitting for ≥30 minutes, or walking up or down stairs). CPHP and functional impairment were assessed via 4- and 6-month phone surveys. RESULTS: Of 216 patients, 72 (33.3%) had high PCS, with mean (SD) of 30.0 (7.9). In contrast, 144 (66.7%) patients had low PCS, with mean (SD) of 9.0 (4.7). At 4 months, 26/63 (41.3%) patients in the high PCS group developed CPHP, compared to 24/109 (22.0%) in the low PCS group. At 6 months, 14/53 (26.4%) high PCS patients developed CPHP, compared to 10/97 (10.3%) patients with low PCS. High PCS was independently associated with CPHP at 4 months (OR 2.49 [95% CI 1.27 to 4.89], p=0.0082) and 6 months (OR 3.12 [95% CI 1.28 to 7.64], p=0.0126) but was not associated with functional impairment. High PCS≥20, presence of evoked mechanical temporal summation (MTS), and history of abdominal/pelvic surgery predict CPHP at 4 months with area under the curve (AUC) of 0.69. Similarly, PCS≥20 and increasing MTS magnitude predicted CPHP at 6 months with AUC of 0.76. CONCLUSION: High PCS was independently associated with CPHP. Future studies should identify other CPHP associated factors to formulate a risk-prediction model and investigate the effectiveness of early intervention for pain catastrophizers in improving pain-related outcomes.

A preliminary assessment of vital-signs-integrated patient-assisted intravenous opioid analgesia (VPIA) for postsurgical pain.

BACKGROUND: We developed a Vital-signs-integrated Patient-assisted Intravenous opioid Analgesia (VPIA) analgesic infusion pump, a closed-loop vital signs monitoring and drug delivery system which embodied in a novel algorithm that took into account patients' vital signs (oxygen saturation, heart rate). The system aimed to allow responsive titration of personalized pain relief to optimize pain relief and reduce the risk of respiratory depression. Moreover, the system would be important to enable continuous monitoring of patients during delivery of opioid analgesia. METHODS: Nineteen patients who underwent elective gynecological surgery with postoperative patient controlled analgesia (PCA) with morphine were recruited. The subjects were followed up from their admission to the recovery room/ ward for at least 24 h until assessment of patient satisfaction on the VPIA analgesic infusion pump. RESULTS: The primary outcome measure of incidence of oxygen desaturation showed all patients had at least one episode of oxygen desaturation (< 95%) during the study period. Only 6 (31.6%) patients had oxygen desaturation that persisted for more than 5 min. The median percentage time spent during treatment that oxygen saturation fell below 95% was 1.9%. Fourteen (73.7%) out of 19 patients encountered safety pause, due to transient oxygen desaturation or bradycardia. The patients' median [IQR] pain scores at rest and at movement after post-op 24 h were 0.0 [2.0] and 3.0 [2.0], respectively. The average morphine consumption in the first 24 h was 12.5 ± 7.1 mg. All patients were satisfied with their experience with the VPIA analgesic infusion pump. CONCLUSIONS: The use of VPIA analgesic infusion pump, when integrated with continuous vital signs monitor and variable lockout algorithm, was able to provide pain relief with good patient satisfaction. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov registry (NCT02804022) on 28 Feb 2016.

A novel approach to neuraxial anesthesia: application of an automated ultrasound spinal landmark identification.

BACKGROUND: Neuraxial procedures are commonly performed for therapeutic and diagnostic indications. Currently, they are typically performed via palpation-guided surface landmark. We devised a novel intelligent image processing system that identifies spinal landmarks using ultrasound images. Our primary aim was to evaluate the first attempt success rate of spinal anesthesia using landmarks obtained from the automated spinal landmark identification technique. METHODS: In this prospective cohort study, we recruited 100 patients who required spinal anesthesia for surgical procedures. The video from ultrasound scan image of the L3/4 interspinous space in the longitudinal view and the posterior complex in the transverse view were recorded. The demographic and clinical characteristics were collected and analyzed based on the success rates of the spinal insertion. RESULTS: Success rate (95%CI) for dural puncture at first attempt was 92.0% (85.0-95.9%). Median time to detection of posterior complex was 45.0 [IQR: 21.9, 77.3] secs. There is good correlation observed between the program-recorded depth and the clinician-measured depth to the posterior complex (r = 0.94). CONCLUSIONS: The high success rate and short time taken to obtain the surface landmark with this novel automated ultrasound guided technique could be useful to clinicians to utilise ultrasound guided neuraxial techniques with confidence to identify the anatomical landmarks on the ultrasound scans. Future research would be to define the use in more complex patients during the administration of neuraxial blocks. TRIAL REGISTRATION: This study was retrospectively registered on clinicaltrials.gov registry ( NCT03535155 ) on 24 May 2018.

Evaluation of association factors for labor episodic pain during epidural analgesia.

PURPOSE: Epidural analgesia provides safe and effective labor pain relief. However, labor episodic pain can occur during epidural analgesia, requiring epidural top-ups, and may result in decreased patient satisfaction. The primary aim of our study was to investigate the factors associated with labor episodic pain during epidural analgesia. PATIENTS AND METHODS: Electronic and hardcopy records of labor deliveries between January 2012 and December 2015 were reviewed at KK Women's and Children's Hospital, Singapore. The primary outcome was the prevalence of episodic pain. Demographic, clinical and anesthetic data were retrieved. Univariate and multivariate logistic regression analyses were used to identify associated risk factors for labor episodic pain experienced by parturients while receiving epidural analgesia. Model performance was assessed by area under the curve (AUC) from the receiver operating characteristic curve. RESULTS: The prevalence of labor episodic pain was 14.2% (2,951 of 20,798 parturients). The risk factors associated with labor episodic pain, which are given here as factor (OR, 95% CI), are the following: need for epidural resiting (11.4, 7.53-17.28), higher pain scores intrapartum (1.34, 1.32-1.36), higher Bromage scores (1.12, 1.02-1.22), the need for instrumental delivery (1.32, 1.16-1.52), the need for cesarean delivery (1.41, 1.26-1.59), the presence of venous puncture (1.29, 1.03-1.62), the presence of dural puncture (14.28, 5.92-34.43), the presence of high block (6.05, 1.39-26.35), the need for a urinary catheter (1.17, 1.17-1.34), larger volumes of local anesthetics used (1.01, 1.01-1.01) and higher body mass index (1.01, 1.01-1.02), and decreased maternal satisfaction (0.97, 0.97-0.98). The AUC was 0.80. CONCLUSION: Knowledge of these factors may allow for future interventions in management to prevent labor episodic pain. Further research is needed to validate these association factors.

Development and validation of a predictive risk factor model for epidural re-siting in women undergoing labour epidural analgesia: a retrospective cohort study.

BACKGROUND: Epidural catheter re-siting in parturients receiving labour epidural analgesia is distressing to the parturient and places them at increased complications from a repeat procedure. The aim of this study was to develop and validate a clinical risk factor model to predict the incidence of epidural catheter re-siting in labour analgesia. METHODS: The data from parturients that received labour epidural analgesia in our centre during 2014-2015 was used to develop a predictive model for epidural catheter re-siting during labour analgesia. Multivariate logistic regression analysis was used to identify factors that were predictive of epidural catheter re-siting. The forward, backward and stepwise variable selection methods were applied to build a predictive model, which was internally validated. The final multivariate model was externally validated with the data collected from 10,170 parturients during 2012-2013 in our centre. RESULTS: Ninety-three (0.88%) parturients in 2014-2015 required re-siting of their epidural catheter. The training data set included 7439 paturients in 2014-2015. A higher incidence of breakthrough pain (OR = 4.42), increasing age (OR = 1.07), an increased pain score post-epidural catheter insertion (OR = 1.35) and problems such as inability to obtain cerebrospinal fluid in combined spinal epidural technique (OR = 2.06) and venous puncture (OR = 1.70) were found to be significantly predictive of epidural catheter re-siting, while spontaneous onset of labour (OR = 0.31) was found to be protective. The predictive model was validated internally on a further 3189 paturients from the data of 2014-2015 and externally on 10,170 paturients from the data of 2012-2013. Predictive accuracy of the model based on C-statistic were 0.89 (0.86, 0.93) and 0.92 (0.88, 0.97) for training and internal validation data respectively. Similarly, predictive accuracy in terms of C-statistic was 0.89 (0.86, 0.92) based on 2012-2013 data. CONCLUSION: Our predictive model of epidural re-siting in parturients receiving labour epidural analgesia could provide timely identification of high-risk paturients required epidural re-siting.

Investigating determinants for patient satisfaction in women receiving epidural analgesia for labour pain: a retrospective cohort study.

BACKGROUND: Epidural analgesia is a popular choice for labour pain relief. Patient satisfaction is an important patient-centric outcome because it can significantly influence both mother and child. However, there is limited evidence in the correlations between clinical determinants and patient satisfaction. We aim to investigate clinical covariates that are associated with low patient satisfaction in parturients receiving labour neuraxial analgesia. METHODS: After institutional ethics approval was obtained, we conducted a retrospective cohort study using electronic and corresponding hardcopy records from 10,170 parturients receiving neuraxial analgesia between the periods of January 2012 to December 2013 in KK Women's and Children's Hospital in Singapore. Demographic, obstetric and anesthetic data were collected. The patient satisfaction scores on the neuraxial labour analgesia was reported by the parturient at 24 to 48 h post-delivery during the post-epidural round conducted by the resident and pain nurse. Parturients were stratified into one of three categories based on their satisfaction scores. Ordinal logistic regression models were used to identify potential covariates of patient dissatisfaction. RESULTS: 10,146 parturients were included into the study, of which 3230 (31.8%) were 'not satisfied', 3646 (35.9%) were 'satisfied', and 3270 (32.2%) were 'very satisfied'. Multivariable ordinal logistic regression analysis showed that instrument-assisted vaginal delivery (p = 0.0007), higher post-epidural pain score (p = 0.0016), receiving epidural catheter resiting (p <  0.0001), receiving neuraxial analgesia at a more advanced cervical dilation (p = 0.0443), multiparity (p = 0.0039), and post-procedure complications headache (p = 0.0006), backache (p <  0.0001), urinary retention (p = 0.0002) and neural deficit (p = 0.0297) were associated with patient dissatisfaction. Chinese, compared with other ethnicities (p = 0.0104), were more likely to be dissatisfied. CONCLUSIONS: Our study has identified several clinical determinants that were independent associated factors for low patient satisfaction. These covariates could be useful in developing a predictive model to detect at-risk parturients and undertake time-sensitive precautionary measures for better patient satisfaction.

Supreme™ laryngeal mask airway use in general Anesthesia for category 2 and 3 Cesarean delivery: a prospective cohort study.

BACKGROUND: The Supreme™ laryngeal mask airway (SLMA) is a single-use LMA with double lumen design that allows separation of the respiratory and the alimentary tract, hence potentially reducing the gastric volume and risk of aspiration. The purpose of this prospective cohort study is to evaluate the the role of the SLMA as an airway technique for women undergoing category 2 and 3 Cesarean delivery under general anesthesia. METHODS: We recruited 584 parturients who underwent category 2 or 3 Cesarean delivery under general anesthesia, in which 193 parturients underwent category 2 and 391 parturients underwent category 3 Cesarean delivery. The primary outcome was insertion success rate at 1st attempt in SLMA insertion. The secondary outcomes included anaesthetic, obstetric outcomes and maternal side effects associated with airway device. RESULTS: The 1st attempt insertion success rate was 98.3%, while the overall insertion success rate was 100%. The mean (Standard deviation) time to effective ventilation was 15.6 (4.4) seconds. Orogastric tube insertion was successful at the 1st attempt in all parturients. There was no clinical evidence of aspiration or regurgitation. No episodes of hypoxemia, laryngospasm or bronchospasm were observed intra-operatively. The incidence of complications was low and with good maternal satisfaction reported. CONCLUSIONS: The SLMA could be an alternative effective airway in category 2 and 3 parturients emergency Cesarean Delivery under general anesthesia in a carefully-selected obstetric population. TRIAL REGISTRATION: Clinical Trials Registration: Clinicaltrials.gov Registration NCT02026882 . Registered on December 31, 2013.

A preliminary assessment of the LMA protector™ in non-paralysed patients.

BACKGROUND: The LMA Protector™ is the latest CE marked single use supraglottic airway device. This airway device provides access and functional separation of the respiratory and digestive tracts. There are two ports (male, female ports) to provide suction in the laryngeal region and insertion of the gastric tube. The aim of our study is to assess the ease of use, airway quality, device positioning, airway leak and complications associated with initial clinical experience in LMA Protector™ usage. METHODS: This is an initial investigation of LMA Protector™ airway device. We conducted a preliminary assessment in the anaesthetised women who underwent minor gynaecological procedures with spontaneous ventilation in order to evaluate the performance of the airway device. RESULTS: Insertion was successful on first and second attempts in 23 (88.5%) and 3 (11.5%) respectively. Median [IQR (range)] insertion time was 19 [17-21(14-58)] seconds. Airway leak pressure was 25.5 [23-29(21-30] cmH2O. On fibreoptic examination via the device, vocal cords were visible in all 26 patients. There were no alternative airway use or airway manipulations required during maintenance of anaesthesia. Six patients had sore throat 24 h after procedures and there was no dysphagia or hoarseness. CONCLUSION: This pilot study of the LMA protector shows that the device is easily inserted with fast insertion time, providing a reliable and adequate airway seal. TRIAL REGISTRATION: Clinicaltrials.gov Registration NCT02531256 . Retrospectively registered on August 21, 2015.

Legal and ethical issues in research.

Legal and ethical issues form an important component of modern research, related to the subject and researcher. This article seeks to briefly review the various international guidelines and regulations that exist on issues related to informed consent, confidentiality, providing incentives and various forms of research misconduct. Relevant original publications (The Declaration of Helsinki, Belmont Report, Council for International Organisations of Medical Sciences/World Health Organisation International Guidelines for Biomedical Research Involving Human Subjects, World Association of Medical Editors Recommendations on Publication Ethics Policies, International Committee of Medical Journal Editors, CoSE White Paper, International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use-Good Clinical Practice) form the literature that are relevant to the ethical and legal aspects of conducting research that researchers should abide by when conducting translational and clinical research. Researchers should note the major international guidelines and regional differences in legislation. Hence, specific ethical advice should be sought at local Ethics Review Committees.

Investigating analgesic and psychological factors associated with risk of postpartum depression development: a case-control study.

AIM: The aim of this study was to investigate the role of peripartum analgesic and psychological factors that may be related to postpartum depression (PPD). METHODS: This case-control study was conducted in pregnant females who delivered at KK Women's and Children's Hospital from November 2010 to October 2013 and had postpartum psychological assessment. Demographic, medical, and postpartum psychological status assessments, intrapartum data including method of induction of labor, mode of labor analgesia, duration of first and second stages of labor, mode of delivery, and pain intensity on hospital admission and after delivery were collected. PPD was assessed using the Edinburgh Postnatal Depression Scale and clinical assessment by the psychiatrist. RESULTS: There were 62 cases of PPD and 417 controls after childbirth within 4-8 weeks. The odds of PPD was significantly lower (33 of 329 [10.0%]) in females who received epidural analgesia for labor compared with those who chose nonepidural analgesia (29 of 150 [19.3%]) ([odds ratio] 0.47 (0.27-0.8), P=0.0078). The multivariate analysis showed that absence of labor epidural analgesia, increasing age, family history of depression, history of depression, and previous history of PPD were independent risk factors for development of PPD. CONCLUSION: The absence of labor epidural analgesia remained as an independent risk factor for development of PPD when adjusted for psychiatric predictors of PPD such as history of depression or PPD and family history of depression.

Proteomics analysis of the expression of neurogranin in murine neuroblastoma (Neuro-2a) cells reveals its involvement for cell differentiation.

Neurogranin (Ng) is a neural-specific, calmodulin (CaM)-binding protein that is phosphorylated by protein kinase C (PKC). Although its biochemical property has been well characterized, the physiological function of Ng needs to be elucidated. In the present study, we performed proteomics analysis of the induced compositional changes due to the expression of Ng in murine neuroblastoma (Neuro-2a) cells using isotope coded affinity tags (ICAT) combined with 2-dimensional liquid chromatography/tandem mass spectrometry (2D-LC/MS/MS). We found that 40% of identified proteins were down-regulated and most of these proteins are microtubule components and associated proteins that mediated neurite outgrowth. Western blot experiments confirmed the expression of alpha-tubulin and microtubule- associated protein 1B (MAP 1B) was dramatically reduced in Neuro-2a-Ng cells compared to control. Cell morphology of Neuro-2a-Ng showed far less neurites than the control. Serum deprivation induced the extension of only one or two long neurites per cell in Neuro-2a-Ng, contrasting to the extension of multiple neurites per control cell. Ng may be linked to neurite formation by affecting expression of several microtubule related proteins. Furthermore, the PKC activator (PMA) induced an enhanced ERK1/2 activity in the cells that expressed Ng. The mutation of Ng at S36A caused sustained increase of ERK1/2 activity, whereas the ERK1/2 activity in mutation at I33Q showed no difference compared to wild type Ng, suggesting the phosphorylation of Ng but not the CaM /Ng interaction plays an important role in ERK activation. Ng may be involved in neuronal growth and differentiation via PKC and ERK1/2 signaling pathways.

Characterization of transcriptional regulation of neurogranin by nitric oxide and the role of neurogranin in SNP-induced cell death: implication of neurogranin in an increased neuronal susceptibility to oxidative stress.

Neurogranin (Ng), a calmodulin (CaM)-binding protein kinase C (PKC) substrate, regulates the availability of Ca(2+)/CaM complex and modulates the homeostasis of intracellular calcium in neurons. Previous work showed Ng oxidation by NO donor induces increase in [Ca(2+)](i). The current study demonstrated that the gene transcription of Ng could be up-regulated by various nitric oxide (NO) donors via a NO-soluble guanylyl cyclase (sGC)-mediated pathway. Furthermore, ectopic expression of neuronal nitric oxide synthase (nNOS) in human embryonic kidney 293 cells (HEK 293) exhibited a nNOS-concentration-dependent biphasic regulatory effect on Ng gene transcription. One of the NO donors, sodium nitroprusside (SNP), however, induced cell death of neuroblastoma Neuro-2a cells. The potency of SNP-induced cell death was shown to be higher in Neuro-2a cells expressing recombinant Ng, as compared with Neuro-2a control cells without Ng expression in cell viability and apoptosis assays. Single-cell fluorescence imaging and site-directed mutagenesis studies suggest that Ng promotes SNP-induced cell death through an amplification of calcium-mediated signaling, which requires the interaction between CaM and IQ motif of Ng. Increased neuronal susceptibility rendered by Ng in response to pathophysiological NO production is suggested to be involved in the selective vulnerability of neurons to oxidative insults in the CNS.