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1.
BMC Palliat Care ; 23(1): 84, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38556855

ABSTRACT

BACKGROUND: The interdisciplinary realm of medical humanities explores narratives and experiences that can enhance medical education for physicians through perspective-taking and reflective practice. However, there is a gap in comprehension regarding its appropriateness at the postgraduate level, especially when utilising art therapists as faculty. This study aims to assess the acceptability of an innovative art therapy-focused educational initiative among junior doctors during a palliative care rotation, with the goal of cultivating empathy and promoting well-being. METHODS: A qualitative research project was conducted at the Division of Supportive and Palliative Care (DSPC) in the National Cancer Centre Singapore (NCCS). The study involved the recruitment of junior doctors who had successfully completed a three-month palliative care rotation program, spanning from January 2020 to April 2021. In a single small-group session lasting 1.5 h, with 3 to 4 participants each time, the individuals participated in activities such as collage making, group reflection, and sharing of artistic creations. These sessions were facilitated by an accredited art therapist and a clinical psychologist, focusing on themes related to empathy and wellbeing. To assess the acceptability of the program, two individual interviews were conducted three months apart with each participant. An independent research assistant utilised a semi-structured question guide that considered affective attitude, burden, perceived effectiveness, coherence, and self-efficacy. Thematic analysis of the transcribed data was then employed to scrutinise the participants' experiences. RESULTS: A total of 20 individual interviews were completed with 11 participants. The three themes identified were lack of pre-existing knowledge of the humanities, promotors, and barriers to program acceptability. CONCLUSIONS: The participants have mixed perceptions of the program's acceptability. While all completed the program in its entirety, the acceptability of the program is impeded by wider systemic factors such as service and manpower needs. It is vital to address these structural limitations as failing to do so risks skewing current ambivalence towards outright rejection of future endeavours to integrate humanities programs into medical education.


Subject(s)
Art Therapy , Palliative Medicine , Humans , Empathy , Qualitative Research , Employment
2.
Article in English | MEDLINE | ID: mdl-38666305

ABSTRACT

OBJECTIVES: To evaluate the performance of an artificial intelligence (AI) and machine learning (ML) model for first-trimester screening for pre-eclampsia in a large Asian population. METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 935 participants with singleton pregnancies attending for routine pregnancy care at 11-13+6 weeks of gestation in seven regions in Asia between December 2016 and June 2018. We applied the AI+ML model for the first-trimester prediction of preterm pre-eclampsia (<37 weeks), term pre-eclampsia (≥37 weeks), and any pre-eclampsia, which was derived and tested in a cohort of pregnant participants in the UK (Model 1). This model comprises maternal factors with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor (PlGF). The model was further retrained with adjustments for analyzers used for biochemical testing (Model 2). Discrimination was assessed by area under the receiver operating characteristic curve (AUC). The Delong test was used to compare the AUC of Model 1, Model 2, and the Fetal Medicine Foundation (FMF) competing risk model. RESULTS: The predictive performance of Model 1 was significantly lower than that of the FMF competing risk model in the prediction of preterm pre-eclampsia (0.82, 95% confidence interval [CI] 0.77-0.87 vs. 0.86, 95% CI 0.811-0.91, P = 0.019), term pre-eclampsia (0.75, 95% CI 0.71-0.80 vs. 0.79, 95% CI 0.75-0.83, P = 0.006), and any pre-eclampsia (0.78, 95% CI 0.74-0.81 vs. 0.82, 95% CI 0.79-0.84, P < 0.001). Following the retraining of the data with adjustments for the PlGF analyzers, the performance of Model 2 for predicting preterm pre-eclampsia, term pre-eclampsia, and any pre-eclampsia was improved with the AUC values increased to 0.84 (95% CI 0.80-0.89), 0.77 (95% CI 0.73-0.81), and 0.80 (95% CI 0.76-0.83), respectively. There were no differences in AUCs between Model 2 and the FMF competing risk model in the prediction of preterm pre-eclampsia (P = 0.135) and term pre-eclampsia (P = 0.084). However, Model 2 was inferior to the FMF competing risk model in predicting any pre-eclampsia (P = 0.024). CONCLUSION: This study has demonstrated that following adjustment for the biochemical marker analyzers, the predictive performance of the AI+ML prediction model for pre-eclampsia in the first trimester was comparable to that of the FMF competing risk model in an Asian population.

3.
NPJ Precis Oncol ; 7(1): 136, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38102334

ABSTRACT

Despite the promising antitumor activity of SHP2 inhibitors in RAS-dependent tumours, overall responses have been limited by their narrow therapeutic window. Like with all MAPK pathway inhibitors, this is likely the result of compensatory pathway activation mechanisms. However, the underlying mechanisms of resistance to SHP2 inhibition remain unknown. The E3 ligase SMURF2 limits TGFß activity by ubiquitinating and targeting the TGFß receptor for proteosome degradation. Using a functional RNAi screen targeting all known phosphatases, we identify that the tyrosine phosphatase SHP2 is a critical regulator of TGFß activity. Specifically, SHP2 dephosphorylates two key residues on SMURF2, resulting in activation of the enzyme. Conversely, SHP2 depletion maintains SMURF2 in an inactive state, resulting in the maintenance of TGFß activity. Furthermore, we demonstrate that depleting SHP2 has significant implications on TGFß-mediated migration, senescence, and cell survival. These effects can be overcome through the use of TGFß-targeted therapies. Consequently, our findings provide a rationale for combining SHP2 and TGFß inhibitors to enhance tumour responses leading to improved patient outcomes.

4.
Prenat Diagn ; 42(11): 1368-1376, 2022 10.
Article in English | MEDLINE | ID: mdl-36089766

ABSTRACT

OBJECTIVE: To investigate preferences of pregnant women for the characteristics of prenatal testing, and to quantify their willingness-to-pay (WTP) for non-invasive prenatal testing (NIPT) as first-line screening for Down Syndrome. METHOD: A cross-sectional discrete choice experiment survey including five testing attributes was administered to 192 pregnant women (≤14 weeks' gestation) who were aged ≥21 years in Singapore. We calculated marginal WTP for improvements in testing characteristics and NIPT. RESULTS: We identified two groups of women with distinct preferences for prenatal testing. Women aged ≥35 years, with at least a university education, and with intention to terminate pregnancy of an affected fetus were more likely to be in the group with higher WTP for improvements in test characteristics. While participants valued increased detection rate and lower screen positive rate associated with NIPT, they also valued no risk of test failure and ability to test for birth defects using standard testing. The participants, on average, were not willing to pay for NIPT over the standard testing as a first-line screening test. CONCLUSIONS: As a first-line screening, NIPT was not preferred over standard testing. The prenatal consultations should focus on each testing characteristic equally as our findings show diverse preferences for testing characteristics.


Subject(s)
Down Syndrome , Cross-Sectional Studies , Down Syndrome/diagnosis , Educational Status , Female , Gestational Age , Humans , Pregnancy , Prenatal Diagnosis
5.
Hypertension ; 79(2): 314-322, 2022 02.
Article in English | MEDLINE | ID: mdl-34689595

ABSTRACT

The study aimed to investigate whether serum sFlt-1 (soluble fms-like tyrosine kinase-1) at 11-13 weeks' gestation in pregnancies that subsequently developed preeclampsia was different from those without preeclampsia and compare screening performance of the International Prediction of Pregnancy Complications (IPPIC) reported models, which include various combinations of maternal factors, systolic blood pressure, diastolic blood pressure, PlGF (placental growth factor) and sFlt-1 and the competing risk (CR) models, which include various combinations of maternal factors, mean arterial pressure (MAP) and PlGF for predicting any-onset, early-onset, and late-onset preeclampsia. This was a prospective multicenter study in 7877 singleton pregnancies. The differences of the predictive performance between the IPPIC and CR models were compared. There were 141 women (1.79%) who developed preeclampsia, including 13 cases (0.17%) of early-onset preeclampsia and 128 cases (1.62%) of late-onset preeclampsia. In pregnancies that developed preeclampsia compared to unaffected pregnancies, median serum sFlt-1 levels and its MoMs were not significantly different (p>0.05). There was no significant association between gestational age at delivery and log10 sFlt-1 and log10 sFlt-1 MoM (p>0.05). The areas under the curve of CR models were significantly higher than the IPPIC models for the prediction of any-onset and late-onset preeclampsia but not for early-onset preeclampsia. In conclusion, there are no significant differences in the maternal serum sFlt-1 levels at 11-13 weeks' gestation between women who subsequently develop preeclampsia and those who do not. Moreover, the CR models for the prediction of any-onset and late-onset preeclampsia perform better than the IPPIC reported model.


Subject(s)
Blood Pressure/physiology , Pre-Eclampsia/diagnosis , Pregnancy Trimester, First/blood , Vascular Endothelial Growth Factor Receptor-1/blood , Adult , Biomarkers , Female , Humans , Placenta Growth Factor/blood , Pre-Eclampsia/blood , Pre-Eclampsia/physiopathology , Pregnancy , Prospective Studies
6.
BMJ Case Rep ; 15(12)2022 Dec 07.
Article in English | MEDLINE | ID: mdl-36593615

ABSTRACT

Gestational diabetes mellitus (GDM) is defined as the first onset of glucose intolerance in pregnancy without prior known diabetes. While it is commonly associated with metabolic risk factors such as obesity and hypertension, a small percentage of women with GDM have underlying autoimmune causes, with presence of islet-cell antibodies resulting in autoimmune-mediated destruction of the pancreas. We present a case of idiopathic postpartum pancreatitis precipitating fulminant diabetic ketoacidosis in a patient with otherwise well-controlled GDM during pregnancy, and subsequent findings of positive anti-glutamic acid decarboxylase antibody. This is the first presentation of autoimmune diabetes diagnosed postnatally in a woman who has no previous medical or family history.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes, Gestational , Pancreatitis , Pregnancy , Female , Humans , Diabetes Mellitus, Type 1/complications , Risk Factors , Postpartum Period , Pancreatitis/diagnosis , Pancreatitis/etiology
7.
Ann Acad Med Singap ; 49(9): 677-683, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33241257

ABSTRACT

The WHO declared the coronavirus disease 2019 (COVID-19) a global pandemic on 11 March 2020. Lessons from SARS epidemic led Singapore to develop stringent infection control protocols in preparation for future pandemics. However, unlike SARS, COVID-19 appears to be more transmissible and is predicted to continue for longer. As of 14 June 2020, there have been 40,197 positive cases with 26 deaths in Singapore, and KK Women's and Children's Hospital (KKH) has managed a total of 73 cases. Obstetrics ultrasound is an indispensable medical service and must continue to operate during a pandemic. A key balance must be struck between keeping patients and healthcare workers safe while being able to provide quality and prompt obstetric care. Our Antenatal Diagnostic Centre (ADC) in KKH developed new strategies to adapt to the pandemic when the national Disease Outbreak Response System Condition (DORSCON) was raised from yellow to orange on 7 February 2020. In this paper, we discuss our clinical workflow to reduce the risk of transmission amongst patients and staff while minimising disruption to our services.


Subject(s)
COVID-19/prevention & control , Delivery of Health Care/methods , Personnel Staffing and Scheduling , Prenatal Care/methods , Ultrasonography, Prenatal/methods , Amniocentesis , COVID-19/diagnosis , COVID-19/transmission , Chorionic Villi Sampling , Delivery of Health Care/organization & administration , Female , Fetoscopy , Hospitals, Maternity , Humans , Patient Isolation , Personal Protective Equipment , Physical Distancing , Pregnancy , Prenatal Care/organization & administration , Singapore
9.
Nat Commun ; 10(1): 4349, 2019 09 25.
Article in English | MEDLINE | ID: mdl-31554791

ABSTRACT

Treatment of muscle-invasive bladder cancer remains a major clinical challenge. Aberrant HGF/c-MET upregulation and activation is frequently observed in bladder cancer correlating with cancer progression and invasion. However, the mechanisms underlying HGF/c-MET-mediated invasion in bladder cancer remains unknown. As part of a negative feedback loop SMAD7 binds to SMURF2 targeting the TGFß receptor for degradation. Under these conditions, SMAD7 acts as a SMURF2 agonist by disrupting the intramolecular interactions within SMURF2. We demonstrate that HGF stimulates TGFß signalling through c-SRC-mediated phosphorylation of SMURF2 resulting in loss of SMAD7 binding and enhanced SMURF2 C2-HECT interaction, inhibiting SMURF2 and enhancing TGFß receptor stabilisation. This upregulation of the TGFß pathway by HGF leads to TGFß-mediated EMT and invasion. In vivo we show that TGFß receptor inhibition prevents bladder cancer invasion. Furthermore, we make a rationale for the use of combinatorial TGFß and MEK inhibitors for treatment of high-grade non-muscle-invasive bladder cancers.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Proto-Oncogene Proteins c-met/genetics , Receptors, Transforming Growth Factor beta/genetics , Urinary Bladder Neoplasms/genetics , Animals , Benzamides/pharmacology , Cell Line, Tumor , Diphenylamine/analogs & derivatives , Diphenylamine/pharmacology , Disease Progression , Epithelial-Mesenchymal Transition/drug effects , Epithelial-Mesenchymal Transition/genetics , Female , Hepatocyte Growth Factor/pharmacology , Humans , Kaplan-Meier Estimate , Mice, Inbred BALB C , Mice, Nude , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Proto-Oncogene Proteins c-met/metabolism , Pyrazoles/pharmacology , Quinolines/pharmacology , Receptors, Transforming Growth Factor beta/antagonists & inhibitors , Receptors, Transforming Growth Factor beta/metabolism , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/metabolism , Xenograft Model Antitumor Assays/methods
10.
Nat Commun ; 10(1): 3245, 2019 07 19.
Article in English | MEDLINE | ID: mdl-31324797

ABSTRACT

Quantum biological electron transfer (ET) essentially involves in virtually all important biological processes such as photosynthesis, cellular respiration, DNA repair, cellular homeostasis, and cell death. However, there is no real-time imaging method to capture biological electron tunnelling in live cells to date. Here, we report a quantum biological electron tunnelling (QBET) junction and its application in real-time optical detection of QBET and the dynamics of ET in mitochondrial cytochrome c during cell life and death process. QBET junctions permit to see the behaviours of electron tunnelling through barrier molecules with different barrier widths. Using QBET spectroscopy, we optically capture real-time ET in cytochrome c redox dynamics during cellular apoptosis and necrosis in living cells. The non-invasive real-time QBET spectroscopic imaging of ET in live cell open a new era in life sciences and medicine by providing a way to capture spatiotemporal ET dynamics and to reveal the quantum biological mechanisms.


Subject(s)
Cell Respiration/physiology , Cytochromes c/metabolism , Electron Transport , Mitochondria/metabolism , Quantum Theory , Apoptosis , Electronics/instrumentation , Electronics/methods , HeLa Cells , Humans , Kinetics , Oxidation-Reduction , Spectrum Analysis/methods
11.
Complement Ther Clin Pract ; 34: 8-12, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30712750

ABSTRACT

Prompt and effective treatment of maternal depression during pregnancy is important as it is an independent predictor of negative maternal and fetal outcomes. Yoga is an increasingly popular non-pharmacological modality. This study thus aimed to undertake a meta-analysis of the efficacy of yoga-based interventions for maternal depression during pregnancy. A total of 8 clinical studies were systematically reviewed, and 6 studies with a total of 405 pregnant mothers were included in the final meta-analysis. Applying per-protocol analysis and a random-effects model, the pooled standardized mean difference (SMD) from baseline depressive score was -0.452 (95% CI: -0.816 to -0.880, P = 0.015), supporting a statistically significant beneficial effect of yoga-based interventions on mood. Overall, yoga-based interventions are a promising non-pharmacological option, however, most trials examined were preliminary, recruited only participants with mild depression, did not blind study participants and had relatively small sample sizes. Larger randomized, controlled trials should be encouraged.


Subject(s)
Depression/therapy , Pregnancy Complications/therapy , Yoga , Female , Humans , Pregnancy , Pregnancy Complications/psychology , Prenatal Care , Treatment Outcome
12.
Electrophoresis ; 40(10): 1457-1477, 2019 05.
Article in English | MEDLINE | ID: mdl-30676660

ABSTRACT

Circulating tumor cells (CTCs) play an essential role in the metastasis of tumors, and thus can serve as a valuable prognostic factor for malignant diseases. As a result, the ability to isolate and characterize CTCs is essential. This review underlines the potential of dielectrophoresis for CTCs enrichment. It begins by summarizing the key performance parameters and challenges of CTCs isolation using microfluidics. The two main categories of CTCs enrichment-affinity-based and label-free methods-are analysed, emphasising the advantages and disadvantages of each as well as their clinical potential. While the main argument in favour of affinity-based methods is the strong specificity of CTCs isolation, the major advantage of the label-free technologies is in preserving the integrity of the cellular membrane, an essential requirement for downstream characterization. Moving forward, we try to answer the main question: "What makes dielectrophoresis a method of choice in CTCs isolation?" The uniqueness of dielectrophoretic CTCs enrichment resides in coupling the specificity of the isolation process with the conservation of the membrane surface. The specificity of the dielectrophoretic method stems from the differences in the dielectric properties between CTCs and other cells in the blood: the capacitances of the malignantly transformed cellular membranes of CTCs differ from those of other cells. Examples of dielectrophoretic devices are described and their performance evaluated. Critical requirements for using dielectrophoresis to isolate CTCs are highlighted. Finally, we consider that DEP has the potential of becoming a cytometric method for large-scale sorting and characterization of cells.


Subject(s)
Cell Separation/methods , Electrophoresis/methods , Neoplastic Cells, Circulating/pathology , Blood Cells/cytology , Blood Cells/pathology , Cell Separation/instrumentation , Cell Survival , Electrodes , Electrophoresis/instrumentation , Equipment Design , Humans
13.
J Womens Health (Larchmt) ; 28(3): 331-338, 2019 03.
Article in English | MEDLINE | ID: mdl-30407100

ABSTRACT

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition associated with substantial mortality and morbidity. Previous studies have suggested a possible link between maternal selective serotonin reuptake inhibitor (SSRI) use and the risk of PPHN. This study aimed to provide an up-to-date review and meta-analysis of the topic. METHODS: Using the search terms [SSRI OR SSRIs OR selective serotonin reuptake inhibitors OR antidepressant OR Prozac OR fluoxetine OR Lexapro OR escitalopram] AND [pregnancy OR maternal OR newborn OR persistent pulmonary hypertension OR PPHN OR neonat* OR fet*], a preliminary search on the PubMed, Medline, EMBASE, Web of Science, and Google Scholar database yielded 7327 articles published in English between January 1, 1960 and October 1, 2017. RESULTS: A total of 9 cohort and case-control studies, with a total of 7,540,265 subjects were systematically reviewed. Random-effects meta-analysis of eight studies revealed a significantly increased risk of PPHN with maternal SSRI use during pregnancy, with a pooled OR of 1.516 (95% confidence interval: 1.035-1.997, p < 0.001). Overall, the absolute increase in risk of PPHN with SSRI use appears small, with an absolute risk difference of 0.619 per 1000 livebirths and a number needed to harm of 1615 women. CONCLUSIONS: Current evidence suggests that there were significantly greater odds of PPHN with SSRI use during pregnancy. However, the clinical significance of this association remains modest and likely outweighed by the potential benefits of treatment of perinatal depression. The risk of PPHN associated with SSRI therapy might not warrant the recommendation to withdraw antidepressant therapy, as evidence from other studies show that untreated perinatal depression presents additional adverse maternal and fetal outcomes. Given the increasing prevalence of maternal depression and consequent use of antidepressant medications, further research with robust longitudinal or randomized, controlled studies and mechanistic investigations are needed.


Subject(s)
Antidepressive Agents/adverse effects , Persistent Fetal Circulation Syndrome/etiology , Selective Serotonin Reuptake Inhibitors/adverse effects , Antidepressive Agents/therapeutic use , Depression/drug therapy , Female , Humans , Infant, Newborn , Persistent Fetal Circulation Syndrome/epidemiology , Pregnancy , Pregnancy Complications/drug therapy , Prenatal Exposure Delayed Effects , Risk Factors , Selective Serotonin Reuptake Inhibitors/therapeutic use
14.
ACS Appl Mater Interfaces ; 10(43): 36622-36627, 2018 Oct 31.
Article in English | MEDLINE | ID: mdl-30300550

ABSTRACT

Oral administration of hydrophobic and poorly intestinal epithelium-permeable drugs is a significant challenge. Herein, we report a new strategy to overcome this problem by using novel, pH-responsive, and membrane-active nanogels as drug carriers. Prepared by simple physical cross-linking of amphiphilic pseudopeptidic polymers with pH-controlled membrane-activity, the size and hydrophobicity-hydrophilicity balance of the nanogels could be well-tuned. Furthermore, the amphiphilic nanogels could release hydrophobic payloads and destabilize cell membranes at duodenum and jejunum pH 5.0-6.0, which suggests their great potential for intestinal drug delivery.


Subject(s)
Drug Carriers/chemistry , Gels , Intestines/drug effects , Nanomedicine/methods , Administration, Oral , Cell Membrane/metabolism , Cross-Linking Reagents/chemistry , Doxorubicin/therapeutic use , Epithelial Cells/metabolism , HeLa Cells , Humans , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Nanoparticles/chemistry , Particle Size , Polyethylene Glycols/chemistry , Polyethyleneimine/chemistry , Polymers
15.
PLoS One ; 12(9): e0185186, 2017.
Article in English | MEDLINE | ID: mdl-28934306

ABSTRACT

OBJECTIVE: To evaluate causes and impact of delay in the door-to-balloon (D2B) time for patients undergoing primary percutaneous coronary intervention (PPCI). SUBJECTS AND METHODS: From January 2009 to December 2012, 1268 patients (86% male, mean age of 58 ± 12 years) presented to our hospital for ST-elevation myocardial infarction (STEMI) and underwent PPCI. They were divided into two groups: Non-delay defined as D2B time ≤ 90 mins and delay group defined as D2B time > 90 mins. Data were collected retrospectively on baseline clinical characteristics, mode of presentation, angiographic findings, therapeutic modality and inhospital outcome. RESULTS: 202 patients had delay in D2B time. There were more female patients in the delay group. They were older and tend to self-present to hospital. They were less likely to be smokers and have a higher prevalence of prior MI. The incidence of posterior MI was higher in the delay group. They also had a higher incidence of triple vessel disease. The 3 most common reasons for D2B delay was delay in the emergency department (39%), atypical clinical presentation (37.6%) and unstable medical condition requiring stabilisation/computed tomographic imaging (26.7%). The inhospital mortality was numerically higher in the delay group (7.4% versus 4.8%, p = 0.12). CONCLUSIONS: Delay in D2B occurred in 16% of our patients undergoing PPCI. Several key factors for delay were identified and warrant further intervention.


Subject(s)
Asian People , Percutaneous Coronary Intervention/methods , ST Elevation Myocardial Infarction/surgery , Coronary Angiography , Female , Hospitals/statistics & numerical data , Humans , Male , Middle Aged , Retrospective Studies , ST Elevation Myocardial Infarction/diagnostic imaging , Time Factors , Treatment Outcome
16.
J Vasc Surg Cases Innov Tech ; 3(1): 20-22, 2017 Mar.
Article in English | MEDLINE | ID: mdl-29349367

ABSTRACT

The cephalic arch is a common location of stenosis, especially in brachiocephalic fistulas. The cephalic arch has a number of anatomic variations. Cephalic arch stenoses are often resistant and have poor primary patency. Here we describe an unusual case of a hemodialysis patient with a single-conduit supraclavicular cephalic arch draining into the external jugular vein presenting with recurrent cephalic arch stenoses and external jugular vein stenosis. In our view, extrinsic compression by the clavicle may contribute to the high rate of recurrence, the lack of complete dilation of even high-pressure balloons, and a theoretically heightened risk of rupture when cutting balloons are used.

17.
J Clin Med Res ; 9(1): 58-63, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27924176

ABSTRACT

BACKGROUND: We studied the safety, effectiveness, and limitations of airway stenting using self-expanding metal stent (SEMS) in patients with malignant central airway obstruction (CAO). METHODS: A retrospective review of records of patients undergoing SEMS placement for malignant CAO during year 2013 - 2014 was done. RESULTS: Sixteen patients (11 males and five females) underwent SEMS placement for malignant CAO. Median (range) age was 66 (54 - 78) years. No perioperative or immediate postoperative complications were seen except acute myocardial infarction (AMI) in one patient. Three patients were transferred to intensive care unit (ICU) for closer monitoring after the procedure and were discharged the next day. All four patients with lung atelectasis on presentation experienced complete re-expansion of the lung post-stenting. The dyspnea was substantially relieved in 14 (87.5%) patients. Two of the three patients who had been intubated were weaned off from the ventilator following stent insertion. Stent patency was maintained until death in all patients except one. Median survival from the date of diagnosis and the date of stent placement in lung cancer, esophageal cancer, and thyroid cancer were 140 (21 - 564) and 85 (15 - 361), 288 (80 - 419) and 61 (60 - 171), and 129 (71 - 187) and 67 (16 - 118) days, respectively. This survival was similar to reported expected survival associated with the underlying malignancy. During follow-up, granulation tissue (n = 1), mucostasis (n = 1), and tumor ingrowth (n = 2) were the most frequently encountered complications. CONCLUSION: SEMSs are safe and effective in reversing respiratory failure caused by malignant CAO, averting premature death, allowing application of cancer targeted therapy, and restoring impending shortened survival to expected life expectancy associated with the underlying malignancy.

18.
J Geriatr Cardiol ; 13(10): 830-835, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27928224

ABSTRACT

OBJECTIVE: To evaluate the clinical characteristics and in-hospital outcomes of elderly South-East Asian patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: From January 2009 to December 2012, 1268 patients (86.4% male, mean age of 58.4 ± 12.2 years) presented to our hospital for ST-elevation myocardial infarction (STEMI) and underwent PPCI. They were divided into two groups: elderly group defined as age ≥ 70 years and non-elderly group defined as age < 70 years. Data were collected retrospectively on baseline clinical characteristics, door-to-balloon (D2B) time, angiographic findings, therapeutic modality and hospital course. RESULTS: The elderly group constituted 19% of the study population with mean age 76.6 ± 5.0 years. There was a higher proportion of female gender and ethnic Chinese patients in the elderly group when compared with the non-elderly group. The former was less likely to be smokers and have a significantly higher prevalence of hypertension. The mean D2B time was significantly longer in the elderly group. They also had a significantly higher incidence of triple vessel disease and obstructive left main disease. The use of radial artery access, glycoprotein 2b/3a inhibitors and drug-eluting stents during PPCI were also significantly lower. In-hospital mortality was significantly higher in the elderly group. The rate of cardiogenic shock and inhospital complications were also significantly higher. CONCLUSIONS: Our registry showed that in-hospital mortality rate in elderly South-East Asian patients undergoing PPCI for STEMI was high. Further studies into the optimal STEMI management strategy for these elderly patients are warranted.

19.
Medicine (Baltimore) ; 95(50): e5619, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27977603

ABSTRACT

To compare the performance of convex probe endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) with conventional endobronchial biopsy (EBB) or transbronchial lung biopsy (TBLB) in patients with mediastinal, and coexisting endobronchial or peripheral lesions.Retrospective review of records of patients undergoing diagnostic EBUS-TBNA and conventional bronchoscopy in 2014.A total of 74 patients had mediastinal, and coexisting endobronchial or peripheral lesions. The detection rate of EBUS-TBNA for mediastinal lesion >1 cm in short axis, EBB for visible exophytic type of endobronchial lesion, and TBLB for peripheral lesion with bronchus sign were 71%, 75%, and 86%, respectively. In contrast, the detection rate of EBUS-TBNA for mediastinal lesion ≤1 cm in short axis, EBB for mucosal hyperemia type of endobronchial lesion, and TBLB for peripheral lesion without bronchus sign were 25%, 63%, and 38%, and improved to 63%, 88%, and 62% respectively by adding EBB or TBLB to EBUS-TBNA, and EBUS-TBNA to EBB or TBLB. Postprocedure bleeding was significantly more common in patients undergoing EBB and TBLB 8 (40%) versus convex probe EBUS-TBNA 2 patients (2.7%, P = 0.0004).EBUS-TBNA is a safer single diagnostic technique compared with EBB or TBLB in patients with mediastinal lesion of >1 cm in size, and coexisting exophytic type of endobronchial lesion, or peripheral lesion with bronchus sign. However, it requires combining with EBB or TBLB and vice versa to optimize yield when mediastinal lesion is ≤1 cm in size, and coexisting endobronchial and peripheral lesions lack exophytic nature, and bronchus sign, respectively.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Lung/pathology , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Bronchi/pathology , Bronchoscopy , Female , Humans , Male , Mediastinum/pathology , Middle Aged , Retrospective Studies , Sensitivity and Specificity
20.
J Vis Exp ; (112)2016 06 22.
Article in English | MEDLINE | ID: mdl-27404554

ABSTRACT

Immune response results from a complex interplay between the antigen non-specific innate immune system and the antigen specific adaptive immune system. The immune system is a constant balance in maintaining tolerance to self-molecules and reacting rapidly to pathogens. Dendritic cells (DCs) are powerful professional antigen presenting cells that link the innate immune system to the adaptive immune system and balance the adaptive response between self and non-self. Depending on the maturation signals, immature dendritic cells can be selectively stimulated to differentiate into immunogenic or tolerogenic DCs. Immunogenic dendritic cells provide proliferation signals to antigen-specific T cells for clonal expansion; while tolerogenic dendritic cells regulate tolerance by antigen-specific T-cell deletion or clonal expansion of regulatory T-cells. Due to this unique property, dendritic cells are highly sought after as therapeutic agents for cancer and autoimmune diseases. Dendritic cells can be loaded with specific antigens in vitro and injected into the human body to mount a specific immune response both immunogenic and tolerogenic. This work presents a means to generate in vitro from monocytes, immature monocyte derived dendritic cells (moDCs), tolerogenic and mature moDCs that differ in surface marker expression, function and metabolic phenotypes.


Subject(s)
Dendritic Cells , Antigens , Humans , Immune Tolerance , T-Lymphocytes, Regulatory
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