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1.
Am J Surg ; 233: 142-147, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38490878

ABSTRACT

BACKGROUND: The objective of this study was to identify factors associated with the use of spleen-conserving surgeries, as well as patient outcomes, on a national scale. METHODS: This retrospective cohort study (2010-2015) included patients (age≥16 years) with splenic injury in the National Trauma Data Bank. Patients who received a total splenectomy or a spleen-conserving surgery were compared for demographics and clinical outcomes. RESULTS: During the study period, 18,425 received a total splenectomy and 1,825 received a spleen-conserving surgery. Total splenectomy was more likely to be performed for patients with age>65 (odds ratio [OR]: 0.63, p â€‹< â€‹0.001), systolic blood pressure<90 (OR: 0.63, p â€‹< â€‹0.001), heart rate>120 (OR: 0.83, p â€‹= â€‹0.007), and high-grade injuries (OR: 0.18, p â€‹< â€‹0.001). Penetrating trauma patients were more likely to undergo a spleen-conserving surgery (OR: 3.31, p â€‹< â€‹0.001). The use of spleen-conserving surgery was associated with a lower risk of pneumonia (OR: 0.79, p â€‹= â€‹0.009) and venous thromboembolism (OR: 0.72, p â€‹= â€‹0.006). CONCLUSIONS: Spleen-conserving surgeries may be considered for patients with penetrating trauma, age<65, hemodynamic stability, and low-grade injuries. Spleen-conserving surgeries have decreased risk of pneumonia and venous thromboembolism.


Subject(s)
Databases, Factual , Spleen , Splenectomy , Humans , Splenectomy/statistics & numerical data , Splenectomy/methods , Female , Male , Spleen/injuries , Spleen/surgery , Retrospective Studies , Middle Aged , Adult , Aged , Treatment Outcome , United States/epidemiology , Organ Sparing Treatments/methods , Organ Sparing Treatments/statistics & numerical data , Young Adult , Adolescent , Postoperative Complications/epidemiology , Injury Severity Score
2.
Front Med (Lausanne) ; 10: 1236715, 2023.
Article in English | MEDLINE | ID: mdl-37942419

ABSTRACT

Introduction: Lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) individuals have an increased scope of healthcare needs and face many barriers to accessing healthcare. However, LGBTQ+ healthcare education remains scarce, and students' understanding of LGBTQ+ healthcare remains largely uncharacterised. This study investigated the knowledge of and attitudes toward LGBTQ+ healthcare among medical students in Singapore and the United Kingdom (UK), two culturally different countries. Methods: Medical students in two medical schools, one in Singapore and the other in the UK, completed self-administered cross-sectional surveys using multiple-choice, Likert scale, and free-text questions to explore their ideas, concerns, and expectations about LGBTQ+ healthcare education within their medical curricula. Results: From 330 responses, students' knowledge levels were moderate overall, with pronounced gaps in certain areas, including terminology, sexual health, and conversion therapy. Deficiencies in knowledge were significantly greater among students in Singapore compared to the UK (p < 0.001), whilst LGBTQ+ students and non-religious students had more positive knowledge and attitudes than students not identifying. At least 78% of students had positive attitudes towards LGBTQ+ individuals, but 84% had not received LGBTQ+-specific medical education. Although junior UK students were more satisfied with the adequacy of teaching by their medical school's incorporation of LGBTQ+ inclusive teaching in a newer curriculum, qualitative analyses suggested that students in both countries wanted to receive more training. Students further suggested improvements to the medical curriculum to meet their needs. Conclusion: Students in both schools lacked understanding of commonly-used terminology and topics such as sexual healthcare despite affirming attitudes towards LGBTQ+ healthcare. Although sociolegal contexts may affect students' perspectives, differences were less than thought, and students were equally keen to provide affirmative care to their patients. They emphasised a need for more formal teaching of LGBTQ+ healthcare professions to overcome healthcare disparities in these communities.

3.
J Paediatr Child Health ; 57(10): 1658-1661, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34021656

ABSTRACT

AIM: Minimally invasive surfactant therapy (MIST) is used to deliver exogenous surfactant to preterm neonates with respiratory distress syndrome. The objective of this study was to review the use of MIST in moderate to late preterm neonates born in a non-tertiary unit. METHODS: A retrospective review was conducted of neonates receiving MIST in a non-tertiary unit. MIST was considered in neonates requiring continuous positive airway pressure ≥ 6 cm H2 O and fraction of inspired oxygen ≥ 0.35. The Hobart method was used to deliver exogenous surfactant. The primary outcome was improvement in respiratory function. Secondary outcomes include intubation and transfer to a tertiary unit. RESULTS: Between 2016 and 2020, 23 infants were treated with MIST. The median gestational age was 33+5  ± 2.7 weeks and mean age of surfactant administration was 6.6 ± 3.6 h. Surfactant administration resulted in a reduction in median fraction of inspired oxygen from 0.3 to 0.21 at 4 h post MIST (P value: 0.001), and a reduction in median positive end-expiratory pressure (PEEP) from 7 to 6 cm H2 O at 24 h post MIST (P value: 0.003). Continuous positive airway pressure support was required for a median period of 3.5 days following MIST. There was respiratory improvement in 52 and 65% of neonates at 4 and 24 h, respectively, following MIST. The incidence of intubation was 13% and transfer to a tertiary unit was 44%. CONCLUSIONS: Use of MIST at this unit improved respiratory outcomes in moderate to late preterm neonates with respiratory distress syndrome. This procedure was well tolerated with few adverse events. Further research evaluating the efficacy of MIST in other non-tertiary units is warranted.


Subject(s)
Pulmonary Surfactants , Respiratory Distress Syndrome, Newborn , Humans , Infant , Infant, Newborn , Infant, Premature , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome, Newborn/drug therapy , Retrospective Studies , Surface-Active Agents
4.
J Hosp Palliat Nurs ; 23(3): 248-255, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33675298

ABSTRACT

Professional and personal development has always been important in the field of palliative care nursing. Now as patients are increasingly culturally diverse, the ability to understand and connect across cultures is also vital. In light of this, a homecare hospice in Singapore collaborated with a nurse consultant based in the United States to pilot a 10-month cross-cultural bidirectional, distance mentoring project. The overarching goal was to explore the profession and personal benefits for nurses and to provide further information for similar international efforts. Before starting the 10-month project, the consultant met and accompanied the Singapore nurses on home visits to better understand the setting and needs. Each of the 6 Singapore home hospice teams (5 adult and 1 pediatric) was matched with a US volunteer mentor, who was an experienced home hospice nurse. The goal for each team and their mentor was to connect by video monthly to share helpful resources, discuss cases for mutual benefit, or develop a quality improvement project. Lessons learned will contribute to the field of international mentoring and collaboration.


Subject(s)
Mentoring , Hospice Care , Hospices , Humans , Mentors , Pilot Projects , United States
5.
J Cardiothorac Vasc Anesth ; 35(12): 3677-3680, 2021 12.
Article in English | MEDLINE | ID: mdl-33478883

ABSTRACT

OBJECTIVES: Patients with Williams-Beuren syndrome are associated with a high risk of hemodynamic collapse during sedation and/or anesthesia, presumably due to occult coronary obstruction. The objective of this study was to determine the association between transthoracic echocardiogram findings and the presence of coronary obstruction to examine if coronary obstruction can be predicted by transthoracic echocardiogram before anesthesia. DESIGN: Retrospective data analysis of patients with Williams-Beuren syndrome who underwent transthoracic echocardiogram, cardiac catheterization, and/or surgical interventions to determine the correlation between echocardiogram findings and the presence of coronary obstruction determined by cardiac catheterization and/or surgery. SETTING: Single-center university teaching hospital. PARTICIPANTS: The study included 49 patients with Williams-Beuren syndrome who underwent transthoracic echocardiogram, cardiac catheterization, and/or surgical interventions. MEASUREMENTS AND MAIN RESULTS: The only variable associated with coronary artery obstruction was the maximum instantaneous gradient (MIG) across the left ventricular outflow tract (LVOT) on a transthoracic echocardiogram. LVOT MIG ≥ 75 mmHg as the optimal cutoff value was associated with coronary artery obstruction (area under the curve 0.659, odds ratio 6.71, 95% CI 1.31-34.35, p = 0.022). CONCLUSION: LVOT gradient can serve as a good predictor of the presence of coronary obstruction in patients with Williams-Beuren syndrome.


Subject(s)
Ventricular Outflow Obstruction , Williams Syndrome , Cardiac Catheterization , Child , Coronary Vessels , Humans , Retrospective Studies , Ventricular Outflow Obstruction/diagnostic imaging , Williams Syndrome/complications , Williams Syndrome/diagnostic imaging
6.
Cancers (Basel) ; 12(9)2020 Aug 24.
Article in English | MEDLINE | ID: mdl-32846967

ABSTRACT

Triple-negative breast cancer (TNBC), characterized by the absence or low expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), is the most aggressive subtype of breast cancer. TNBC accounts for about 15% of breast cancer cases in the U.S., and is known for high relapse rates and poor overall survival (OS). Chemo-resistant TNBC is a genetically diverse, highly heterogeneous, and rapidly evolving disease that challenges our ability to individualize treatment for incomplete responders and relapsed patients. Currently, the frontline standard chemotherapy, composed of anthracyclines, alkylating agents, and taxanes, is commonly used to treat high-risk and locally advanced TNBC. Several FDA-approved drugs that target programmed cell death protein-1 (Keytruda) and programmed death ligand-1 (Tecentriq), poly ADP-ribose polymerase (PARP), and/or antibody drug conjugates (Trodelvy) have shown promise in improving clinical outcomes for a subset of TNBC. These inhibitors that target key genetic mutations and specific molecular signaling pathways that drive malignant tumor growth have been used as single agents and/or in combination with standard chemotherapy regimens. Here, we review the current TNBC treatment options, unmet clinical needs, and actionable drug targets, including epidermal growth factor (EGFR), vascular endothelial growth factor (VEGF), androgen receptor (AR), estrogen receptor beta (ERß), phosphoinositide-3 kinase (PI3K), mammalian target of rapamycin (mTOR), and protein kinase B (PKB or AKT) activation in TNBC. Supported by strong evidence in developmental, evolutionary, and cancer biology, we propose that the K-RAS/SIAH pathway activation is a major tumor driver, and SIAH is a new drug target, a therapy-responsive prognostic biomarker, and a major tumor vulnerability in TNBC. Since persistent K-RAS/SIAH/EGFR pathway activation endows TNBC tumor cells with chemo-resistance, aggressive dissemination, and early relapse, we hope to design an anti-SIAH-centered anti-K-RAS/EGFR targeted therapy as a novel therapeutic strategy to control and eradicate incurable TNBC in the future.

7.
Ann Breast Cancer Ther ; 4(1): 48-57, 2020 May 02.
Article in English | MEDLINE | ID: mdl-32542231

ABSTRACT

Chemo-resistant breast cancer is a major barrier to curative treatment for a significant number of women with breast cancer. Neoadjuvant chemotherapy (NACT) is standard first- line treatment for most women diagnosed with high-risk TNBC, HER2+, and locally advanced ER+ breast cancer. Current clinical prognostic tools evaluate four clinicopathological factors: Tumor size, LN status, pathological stage, and tumor molecular subtype. However, many similarly treated patients with identical residual cancer burden (RCB) following NACT experience distinctly different tumor relapse rates, clinical outcomes and survival. This problem is particularly apparent for incomplete responders with a high-risk RCB classification following NACT. Therefore, there is a pressing need to identify new prognostic and predictive biomarkers, and develop novel curative therapies to augment current standard of care (SOC) treatment regimens to save more lives. Here, we will discuss these unmet needs and clinical challenges that stand in the way of precision medicine and personalized cancer therapy.

10.
PLoS One ; 14(9): e0221305, 2019.
Article in English | MEDLINE | ID: mdl-31553731

ABSTRACT

OBJECTIVES: We aimed to study the prevalence of CTCs in breast cancer (BC) patients undergoing neoadjuvant or palliative therapy with a label-free microfluidic platform (ClearCell FX), and its prognostic relevance in metastatic BC (mBC). MATERIALS AND METHODS: Peripheral blood samples were collected from 108 BC patients before starting a new line of treatment ("baseline"), majority of whom had mBC (76/108; 70.4%). CTCs were retrieved by dean flow fractionation that enriched for larger cells, and enumerated using immunofluorescence-based staining. Progression-free survival (PFS) in mBC patients was analysed using Kaplan-Meier method; cox proportional hazard models were used for univariable and multivariable analyses. RESULTS: The detection rate of CTCs before starting a new line of treatment was 75.9% (n = 108; median: 8 CTCs/7.5 ml blood) at a cut off of ≥2 CTCs. PFS was inferior for mBC patients with baseline CTC count ≥5 CTCs/7.5 ml blood vs. those with < 5 CTCs/7.5 ml blood (median PFS: 4.3 vs. 7.0 months; p-value: 0.037). The prognostic relevance of CTCs was most significant in patients with HER2- mBC (median PFS: 4.1 vs. 8.3 months; p-value: 0.032), luminal (HR+HER2-) subtype (median PFS: 4.2 vs. 8.3 months; p-value: 0.048), and patients who had one or more prior treatments (median PFS: 4.2 vs. 7.0 months; p-value: 0.02). On multivariable analysis, baseline CTC level (hazard ratio (HR): 1.84, p-value: 0.02) and pre-treatment status (HR: 1.87, p-value: 0.05) were independent predictors of PFS. CONCLUSIONS: This work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform.


Subject(s)
Breast Neoplasms/blood , Neoplastic Cells, Circulating/pathology , Adult , Aged , Asian People , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Count , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Microfluidics , Middle Aged , Prognosis , Progression-Free Survival , Prospective Studies , Receptor, ErbB-2/metabolism , Singapore
11.
Paediatr Anaesth ; 29(8): 799-807, 2019 08.
Article in English | MEDLINE | ID: mdl-31233654

ABSTRACT

BACKGROUND: Self-made Y-connector jet-oxygenation devices with wide-bore expiratory port have been described but not evaluated in infant models. Little is known about the effect of oxygen flow rates on jet oxygenation via transtracheal cannula. AIMS: The aim of this study was to compare two self-made Y-connector jet-oxygenation devices against the ENK oxygen flow modulator™, and the effects of three different oxygen flow rates based on body weight, in both unobstructed and obstructed airways, on the time to re-oxygenate in a rabbit infant model. The aim was also to assess the effectiveness of an oxygen flow rate of 1 L/min, for re-oxygenation using ENK oxygen flow modulator™. METHODS: Nine rabbits were grouped in threes: Group 1 had a Y-connector attached to an intravenous infusion tubing, Group 2 the same Y-connector attached to a perfusion oxygenator tubing and Group 3, ENK oxygen flow modulator™. From oxygen saturations of 75%, the rabbits were jet oxygenated using their assigned device for 10 minutes at each flow rate of 1 L/kg/min, 1.5 L/kg/min and 2 L/kg/min with their airways unobstructed and later, obstructed. Group 3 had additional experiments involving an absolute oxygen flow rate of 1 L/min. RESULTS: All devices resulted in rapid re-oxygenation within 40 seconds at flow rates of 1 L/kg/min. Oxygen flow rates beyond 1 L/kg/min in obstructed airways resulted in high airway pressures. All rabbits in Group 3 with obstructed airways died from barotrauma when jet oxygenated at a flow rate of 1.5 L/kg/min. When an oxygen flow rate of 1 L/min was used in Group 3, there was a failure to re-oxygenate to SpO2 90% within 120 seconds in some rabbits. CONCLUSION: Our animal model results suggest that self-made Y-connector jet-oxygenation devices with wide-bore expiratory port are efficacious and perhaps safer than ENK oxygen flow modulator™ in obstructed airways, and jet oxygenation with minimal oxygen flow rates starting at 1 L/kg/min or (age [years] + 4) L/min, whichever lower, should be considered.


Subject(s)
High-Frequency Jet Ventilation/instrumentation , Intubation, Intratracheal/methods , Respiration, Artificial/methods , Airway Obstruction , Animals , Disease Models, Animal , Equipment Design , Rabbits
12.
BMC Anesthesiol ; 18(1): 161, 2018 11 07.
Article in English | MEDLINE | ID: mdl-30404608

ABSTRACT

BACKGROUND: The Auditory brainstem implant (ABI) is a new surgical option for hearing impaired children. Intraoperative neurophysiology monitoring includes brainstem mapping of cranial nerve (CN) IX, X, XI, XII and their motor nuclei, and corticobulbar tract motor-evoked potential. These require laryngeal electrodes and intra-oral pins, posing a challenge to airway management especially in the pediatric airway, where specialized electromyogram (EMG) tracheal tubes are not available. Challenges include determining the optimum position on the endotracheal tube (ETT) in which to place laryngeal electrode, and the increase in external diameter of ETT contributed by the wrapping the electrode around the shaft of ETT; this may necessitate downsizing of the tracheal tube. An appropriate size ETT minimizes displacement, which in turn can affect electrode contact with the vocal cords. Finally, a small thus crowded pediatric airway makes for difficult visualization during placement of intraoral neuromonitoring electrodes. The use of a videolaryngoscope helps determine optimum electrode placement. CASE PRESENTATION: We describe intraoperative neurophysiology monitoring and airway management for the first two ABI procedures in Singapore, conducted for children with congenitally absent cochlear nerves. CONCLUSION: Neurophysiology cranial nerve IX, X, XII monitoring in the ABI procedure requires intraoral placement of electrodes. Care should be exercised during placement and removal. Vagus nerve monitoring in children requires attention to tube preparation, and consideration should be given to avoidance of airway topicalization.


Subject(s)
Auditory Brain Stem Implants , Cochlear Nerve/abnormalities , Cochlear Nerve/surgery , Intraoperative Neurophysiological Monitoring/methods , Child , Female , Humans , Intraoperative Neurophysiological Monitoring/instrumentation , Male
13.
Cancers (Basel) ; 10(5)2018 May 14.
Article in English | MEDLINE | ID: mdl-29757973

ABSTRACT

Oncogenic K-RAS mutations are found in virtually all pancreatic cancers, making K-RAS one of the most targeted oncoproteins for drug development in cancer therapies. Despite intense research efforts over the past three decades, oncogenic K-RAS has remained largely "undruggable". Rather than targeting an upstream component of the RAS signaling pathway (i.e., EGFR/HER2) and/or the midstream effector kinases (i.e., RAF/MEK/ERK/PI3K/mTOR), we propose an alternative strategy to control oncogenic K-RAS signal by targeting its most downstream signaling module, Seven-In-Absentia Homolog (SIAH). SIAH E3 ligase controls the signal output of oncogenic K-RAS hyperactivation that drives unchecked cell proliferation, uncontrolled tumor growth, and rapid cancer cell dissemination in human pancreatic cancer. Therefore, SIAH is an ideal therapeutic target as it is an extraordinarily conserved downstream signaling gatekeeper indispensable for proper RAS signaling. Guided by molecular insights and core principles obtained from developmental and evolutionary biology, we propose an anti-SIAH-centered anti-K-RAS strategy as a logical and alternative anticancer strategy to dampen uncontrolled K-RAS hyperactivation and halt tumor growth and metastasis in pancreatic cancer. The clinical utility of developing SIAH as both a tumor-specific and therapy-responsive biomarker, as well as a viable anti-K-RAS drug target, is logically simple and conceptually innovative. SIAH clearly constitutes a major tumor vulnerability and K-RAS signaling bottleneck in pancreatic ductal adenocarcinoma (PDAC). Given the high degree of evolutionary conservation in the K-RAS/SIAH signaling pathway, an anti-SIAH-based anti-PDAC therapy will synergize with covalent K-RAS inhibitors and direct K-RAS targeted initiatives to control and eradicate pancreatic cancer in the future.

14.
Mol Neurobiol ; 55(7): 5741-5756, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29043558

ABSTRACT

Sphingomyelinases are a family of enzymes that hydrolyze sphingomyelin to generate phosphocholine and ceramide. The brain distribution and function of neutral sphingomyelinase 2 (nSMase2) were elucidated in this study. nSMase2 mRNA expression was greatest in the striatum, followed by the prefrontal cortex, hippocampus, cerebellum, thalamus, brainstem, and olfactory bulb. The striatum had the highest level of nSMase2 protein expression, followed by the prefrontal cortex, thalamus, hippocampus, brainstem, and cerebellum. Dense immunolabeling was observed in the striatum, including the caudate-putamen, while moderately dense staining was found in the olfactory bulb and cerebral neocortex. Electron microscopy of the caudate-putamen showed nSMase2 immunoreaction product was present in small diameter dendrites or dendritic spines, that formed asymmetrical synapses with unlabeled axon terminals containing small round vesicles; and characteristics of glutamatergic axons. Lipidomic analysis of the striatum showed increase in long chain sphingomyelins, SM36:1 and SM38:1 after inhibition of nSMase activity. Quantitative proteomic analysis of striatal lipid raft fraction showed many proteins were downregulated by more than 2-fold after inhibition or antisense knockdown of nSMase; consistent with the notion that nSMase2 activity is important for aggregation or clustering of proteins in lipid rafts. Inhibition or antisense knockdown of nSMase2 in the caudate-putamen resulted in motor deficits in the rotarod and narrow beam tests; as well as decreased acoustic startle and improved prepulse inhibition of the startle reflex. Together, results indicate an important function of nSMase2 in the striatum.


Subject(s)
Corpus Striatum/enzymology , Membrane Microdomains/metabolism , Motor Activity , Sphingomyelin Phosphodiesterase/metabolism , Animals , Corpus Striatum/cytology , Corpus Striatum/ultrastructure , Gene Expression Regulation, Enzymologic , Gene Knockdown Techniques , Isoenzymes/genetics , Isoenzymes/metabolism , Male , Prepulse Inhibition , Proteome/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Wistar , Reflex, Acoustic , Reflex, Startle , Rotarod Performance Test , Sphingolipids/metabolism , Sphingomyelin Phosphodiesterase/genetics
16.
EBioMedicine ; 11: 183-198, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27569656

ABSTRACT

BACKGROUND: Metastatic breast cancer exhibits diverse and rapidly evolving intra- and inter-tumor heterogeneity. Patients with similar clinical presentations often display distinct tumor responses to standard of care (SOC) therapies. Genome landscape studies indicate that EGFR/HER2/RAS "pathway" activation is highly prevalent in malignant breast cancers. The identification of therapy-responsive and prognostic biomarkers is paramount important to stratify patients and guide therapies in clinical oncology and personalized medicine. METHODS: In this study, we analyzed matched pairs of tumor specimens collected from 182 patients who received neoadjuvant systemic therapies (NST). Statistical analyses were conducted to determine whether EGFR/HER2/RAS pathway biomarkers and clinicopathological predictors, alone and in combination, are prognostic in breast cancer. FINDINGS: SIAH and EGFR outperform ER, PR, HER2 and Ki67 as two logical, sensitive and prognostic biomarkers in metastatic breast cancer. We found that increased SIAH and EGFR expression correlated with advanced pathological stage and aggressive molecular subtypes. Both SIAH expression post-NST and NST-induced changes in EGFR expression in invasive mammary tumors are associated with tumor regression and increased survival, whereas ER, PR, and HER2 were not. These results suggest that SIAH and EGFR are two prognostic biomarkers in breast cancer with lymph node metastases. INTERPRETATION: The discovery of incorporating tumor heterogeneity-independent and growth-sensitive RAS pathway biomarkers, SIAH and EGFR, whose altered expression can be used to estimate therapeutic efficacy, detect emergence of resistant clones, forecast tumor regression, differentiate among partial responders, and predict patient survival in the neoadjuvant setting, has a clear clinical implication in personalizing breast cancer therapy. FUNDING: This work was supported by the Dorothy G. Hoefer Foundation for Breast Cancer Research (A.H. Tang); Center for Innovative Technology (CIT)-Commonwealth Research Commercialization Fund (CRCF) (MF14S-009-LS to A.H. Tang), and National Cancer Institute (CA140550 to A.H. Tang).


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/mortality , ErbB Receptors/metabolism , Nuclear Proteins/metabolism , Signal Transduction , Ubiquitin-Protein Ligases/metabolism , ras Proteins/metabolism , Biomarkers, Tumor , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Disease Progression , ErbB Receptors/genetics , Female , Gene Expression , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Models, Biological , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Nuclear Proteins/genetics , Prognosis , Proportional Hazards Models , Treatment Outcome , Ubiquitin-Protein Ligases/genetics , ras Proteins/genetics
17.
Oxf Med Case Reports ; 2015(6): 303-5, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26069842

ABSTRACT

Ultrasound-guided cannulation of a central venous catheter into the internal jugular vein (IJV) was performed in the intensive care unit for a critically ill patient. The catheter was inserted into the subclavian artery distally, despite prior ultrasound confirmation of the guidewire position using both the in-plane and out-of-plane views. The catheter was removed successfully by the interventional radiologist with a closure device. To our knowledge, there have been previous case reports of subclavian artery injury during IJV cannulation with ultrasound guidance, but rarely in the setting whereby the guidewire was visualized before dilatation and railroading of the catheter. This case demonstrates that the confirmation of the guidewire in the proximal segment of the vein is insufficient to exclude arterial cannulation.

18.
BMC Med Genomics ; 7: 23, 2014 May 13.
Article in English | MEDLINE | ID: mdl-24885028

ABSTRACT

BACKGROUND: Clinical specimens undergoing diagnostic molecular pathology testing are fixed in formalin due to the necessity for detailed morphological assessment. However, formalin fixation can cause major issues with molecular testing, as it causes DNA damage such as fragmentation and non-reproducible sequencing artefacts after PCR amplification. In the context of massively parallel sequencing (MPS), distinguishing true low frequency variants from sequencing artefacts remains challenging. The prevalence of formalin-induced DNA damage and its impact on molecular testing and clinical genomics remains poorly understood. METHODS: The Cancer 2015 study is a population-based cancer cohort used to assess the feasibility of mutational screening using MPS in cancer patients from Victoria, Australia. While blocks were formalin-fixed and paraffin-embedded in different anatomical pathology laboratories, they were centrally extracted for DNA utilising the same protocol, and run through the same MPS platform (Illumina TruSeq Amplicon Cancer Panel). The sequencing artefacts in the 1-10% and the 10-25% allele frequency ranges were assessed in 488 formalin-fixed tumours from the pilot phase of the Cancer 2015 cohort. All blocks were less than 2.5 years of age (mean 93 days). RESULTS: Consistent with the signature of DNA damage due to formalin fixation, many formalin-fixed samples displayed disproportionate levels of C>T/G>A changes in the 1-10% allele frequency range. Artefacts were less apparent in the 10-25% allele frequency range. Significantly, changes were inversely correlated with coverage indicating high levels of sequencing artefacts were associated with samples with low amounts of available amplifiable template due to fragmentation. The degree of fragmentation and sequencing artefacts differed between blocks sourced from different anatomical pathology laboratories. In a limited validation of potentially actionable low frequency mutations, a NRAS G12D mutation in a melanoma was shown to be a false positive. CONCLUSIONS: These findings indicate that DNA damage following formalin fixation remains a major challenge in laboratories working with MPS. Methodologies that assess, minimise or remove formalin-induced DNA damaged templates as part of MPS protocols will aid in the interpretation of genomic results leading to better patient outcomes.


Subject(s)
Artifacts , High-Throughput Nucleotide Sequencing/methods , Mutation/genetics , Neoplasms/genetics , Tissue Fixation , Cell Line, Tumor , DNA Fragmentation , False Positive Reactions , Formaldehyde , Humans , Paraffin Embedding , Polymerase Chain Reaction , Prospective Studies , Sequence Analysis, DNA , Templates, Genetic , Uracil-DNA Glycosidase/metabolism
19.
J Palliat Med ; 17(5): 575-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24708221

ABSTRACT

INTRODUCTION: We devised a comfort care kit (CCK) consisting of nonoral and nonparenteral rescue medications for caregivers to use at home for symptom control in imminently dying patients who have lost their ability to swallow. The aim of this study was to evaluate the feasibility of the CCK from the perspective of bereaved caregivers. METHODS: CCKs were handed out to caregivers for patients who were entered into the care for the dying pathway (CDP). Each CCK includes morphine and haloperidol ampoules, lorazepam tablets, atropine drops, and paracetamol suppositories given either through sublingual or rectal route. We conducted a telephone survey of bereaved caregivers to assess CCK's feasibility (proportion of use), pattern of use, perceived benefits and challenges, and need to transfer to emergency department at the end of life. RESULTS: Forty-nine caregivers completed the survey. Thirty-three (67%) reported that they used the CCK. A majority (76%) only used one medication from the kit. Atropine drops were the most commonly used, followed by morphine and paracetamol. All family members reported that the CCK was easy to use and 98% found it to be effective for symptom management. All except one patient died at home. CONCLUSION: The CCK was feasible and perceived to be effective for symptom control and easy to use. Further research is necessary to optimize the use of this kit and to document related outcomes.


Subject(s)
Administration, Rectal , Administration, Sublingual , Caregivers/psychology , Deglutition Disorders/etiology , Home Care Services/organization & administration , Palliative Care/methods , Terminally Ill , Acetaminophen/administration & dosage , Adjuvants, Anesthesia/administration & dosage , Adult , Aged , Aged, 80 and over , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Opioid/administration & dosage , Anti-Anxiety Agents/administration & dosage , Antipsychotic Agents/administration & dosage , Atropine/administration & dosage , Deglutition Disorders/complications , Female , Haloperidol/administration & dosage , Home Care Services/standards , Humans , Lorazepam/administration & dosage , Male , Middle Aged , Morphine/administration & dosage , Pilot Projects , Singapore
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