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1.
Health Aff (Millwood) ; 43(5): 707-716, 2024 May.
Article in English | MEDLINE | ID: mdl-38709965

ABSTRACT

In July 2020, Hong Kong extended statutory paid maternity leave from ten weeks to fourteen weeks to align with International Labour Organization standards. We used the policy enactment as an observational natural experiment to assess the mental health implications of this policy change on probable postnatal depression (Edinburgh Postnatal Depression Scores of 10 or higher) and postpartum emotional well-being. Using an opportunistic observational study design, we recruited 1,414 survey respondents with births before (August 1-December 10, 2020) and after (December 11, 2020-July 18, 2022) policy implementation. Participants had a mean age of thirty-two, were majority primiparous, and were mostly working in skilled occupations. Our results show that the policy was associated with a 22 percent decrease in mothers experiencing postnatal depressive symptoms and a 33 percent decrease in postpartum emotional well-being interference. Even this modest change in policy, an additional four weeks of paid leave, was associated with significant mental health benefits. Policy makers should consider extending paid maternity leave to international norms to improve mental health among working mothers and to support workforce retention.


Subject(s)
Depression, Postpartum , Mental Health , Mothers , Parental Leave , Humans , Hong Kong , Female , Adult , Depression, Postpartum/epidemiology , Mothers/psychology , Surveys and Questionnaires , Women, Working/psychology , Women, Working/statistics & numerical data , Pregnancy , Maternal Health
2.
AJNR Am J Neuroradiol ; 44(11): 1345-1351, 2023 11.
Article in English | MEDLINE | ID: mdl-37918938

ABSTRACT

BACKGROUND AND PURPOSE: Vertebral compression fracture represents a major health burden for the aging populations globally. However, limited studies exist on the relative efficacy and safety of surgical interventions for vertebral compression fracture. Here, we aim to compare clinical and patient-reported outcomes following vertebral augmentation using balloon kyphoplasty, vertebroplasty, and SpineJack vertebral implant. MATERIALS AND METHODS: An institutional review board-approved, retrospective, multi-institutional review of patients undergoing vertebral augmentation with kyphoplasty, vertebroplasty, and/or a SpineJack vertebral implant was performed between 2018 and 2021. Primary outcomes included pre- and postprocedural pain ratings and vertebral body height restoration. The secondary outcome was a change in the local kyphotic angle. The Kruskal-Wallis test was used to compare outcomes across 3 treatment options. Complications were reviewed during and 30-90 days after the procedure. RESULTS: Vertebral augmentation of 344 vertebral compression fracture levels was performed during the study period. Sixty-seven patients had 79 kyphoplasty procedures (55% women; mean age, 64.2 [SD, 12.3] years). Seventy-four patients underwent a mean of 84 vertebroplasty procedures (51% women; mean age, 63.5 [SD, 12.8] years), and 61 patients had a mean of 67 SpineJack vertebral implant procedures (57.4% women; mean age, 68.3 [SD, 10.6] years). Following kyphoplasty, vertebroplasty, and SpineJack vertebral implant, pain scores improved significantly (P < .001). Resting pain improvement was similar across the 3 procedures, whereas improvement of "worst pain" was significantly better following a SpineJack vertebral implant compared with kyphoplasty and vertebroplasty (P < .001). Patients with a SpineJack vertebral implant had greater improvement in vertebral body height restoration and local kyphotic angle compared with those undergoing kyphoplasty and vertebroplasty. Adjacent level fractures (6.7% incidence) occurred similarly in the 3 procedure types. There were no other peri- or postoperative complications. CONCLUSIONS: The SpineJack vertebral implant showed equivalent pain improvement compared with vertebroplasty and kyphoplasty, but it had superior vertebral body height restoration and local kyphotic angle improvement. This study supports the SpineJack vertebral implant as a safe and effective alternative (adjunct) for vertebral augmentation, especially in patients with moderate-to-severe vertebral compression fractures for greater improvement in vertebral body height restoration.


Subject(s)
Fractures, Compression , Kyphoplasty , Osteoporotic Fractures , Spinal Fractures , Vertebroplasty , Humans , Female , Middle Aged , Aged , Male , Kyphoplasty/methods , Fractures, Compression/diagnostic imaging , Fractures, Compression/surgery , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery , Spinal Fractures/complications , Retrospective Studies , Treatment Outcome , Bone Cements/therapeutic use , Vertebroplasty/methods , Pain/drug therapy , Pain/etiology , Osteoporotic Fractures/surgery
3.
J Vasc Interv Radiol ; 34(4): 660-668, 2023 04.
Article in English | MEDLINE | ID: mdl-36543319

ABSTRACT

PURPOSE: To evaluate safety and effectiveness of percutaneous biliary endoscopy (PBE) performed on patients ineligible for surgery or endoscopic retrograde cholangiopancreatography. MATERIALS AND METHODS: Retrospective review was conducted for all patients who underwent PBE at a single academic institution between June 2013 and February 2020; 39 patients underwent 58 choledochoscopy sessions, and 21 patients underwent 48 cholecystoscopy sessions. Choledochoscopy indications included stone removal (23 of 39 patients) or biliary stenosis evaluation (19 of 39 patients). Cholecystoscopy indications included calculous cholecystitis (18 of 21 patients) and symptomatic cholelithiasis (3 of 21 patients). Technical success, procedural and fluoroscopy times, and tube-free survival were assessed. RESULTS: For all PBEs performed for stone clearance, using disposable endoscopes led to shorter mean ± SD procedural (128.7 minutes ± 56.2 vs 240.2 minutes ± 184.6; P < .01) and fluoroscopy times (10.7 minutes ± 7.9 vs 16.5 minutes ± 12.0; P = .01) than using reusable endoscopes. Increasing institutional experience was associated with reduced procedural time (ß = -56.73; P < .001). Choledochoscopy technical success was 94.8% with 1 adverse event of bile duct perforation with bile leak requiring drainage. For patients with choledocholithiasis, biliary drains were removed in 14 (60.9%) patients, with a mean tube-free survival of 22.1 months ± 23.8. For cholecystoscopy, technical success was 93.8% with no adverse events. Cholecystostomy tubes were removed in 15 (71.4%) patients, with a mean tube-free survival of 7.5 months ± 8.8. CONCLUSIONS: This study supports PBE as a safe and feasible option for nonsurgical patients or those with altered anatomy precluding endoscopic retrograde cholangiopancreatography. Moreover, PBE may result in tube-free survival.


Subject(s)
Cholecystitis , Cholecystostomy , Humans , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholecystitis/surgery , Drainage , Retrospective Studies , Treatment Outcome
4.
BMC Med Educ ; 22(1): 482, 2022 Jun 22.
Article in English | MEDLINE | ID: mdl-35729562

ABSTRACT

BACKGROUND: Asian American (AsAm) representation is lacking in conversations surrounding cultural humility in healthcare. We aimed to investigate US medical student perspectives on AsAm patient inclusion in cultural humility training in medical education. METHODS: This qualitative study analyzed free-text responses to an optional, open-ended question presented at the conclusion of an online survey assessing medical student experiences with and perceptions regarding AsAm patients in their medical education. This survey was distributed to a convenience sample of nine US medical schools. Medical students who completed at least one clinical rotation were eligible to participate in the survey. Qualitative analysis of free-text responses was conducted in an iterative process to generate emergent themes. RESULTS: There was a total of 195 optional free-text responses from 688 participants (28%). Motivation to learn about AsAm population included shared identity and desire to better serve the AsAm population in their local community and future careers. Topics of interest included healthcare-related cultural preferences, healthcare delivery strategies, and health disparities for the AsAm population and other minority patients. Students reported that they drew on personal experiences and some pre-clinical or clinical exposures to learn about AsAm patients. Respondents cited the lack of exposure in the medical school curriculum and clinical experiences as the main challenge to learning about AsAm health and provided suggestions for the delivery of this education in their pre-clinical and clinical education. Respondents emphasized that AsAms are treated as a monolith in medical education and healthcare, despite their heterogeneity. CONCLUSIONS: Medical students identified a need and interest for greater inclusion of AsAm topics in medical education on cultural humility and minority health.


Subject(s)
Education, Medical, Undergraduate , Education, Medical , Students, Medical , Asian , Curriculum , Humans
5.
Pain ; 163(10): e1041-e1053, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35121696

ABSTRACT

ABSTRACT: This study examined the efficacy of internet-delivered cognitive and behavioural interventions for adults with chronic pain AND explored the role of clinical and study characteristics as moderators of treatment effects. PubMed, Embase, PsycINFO, CENTRAL and CINAHL were searched to identify randomized controlled trials published up to October 2021. A meta-analysis of 36 studies (5778 participants) was conducted, which found small effect sizes for interference/disability (Hedges' g = 0.28; 95% confidence interval [CI] 0.21-0.35), depression ( g = 0.43; 95% CI 0.33-0.54), anxiety ( g = 0.32; 95% CI 0.24-0.40), pain intensity ( g = 0.27; 95% CI 0.21-0.33), self-efficacy ( g = 0.39; 95% CI 0.27-0.52) and pain catastrophizing ( g = 0.31; 95% CI 0.22-0.39). Moderator analyses found that interventions which involved clinician guidance had significantly greater effect sizes for interference/disability ( g = 0.38), anxiety ( g = 0.39), and pain intensity ( g = 0.33) compared with those without ( g = 0.16, g = 0.18, and g = 0.20, respectively). Studies using an inactive control had greater effects for depression ( g = 0.46) compared with active control trials ( g = 0.22). No differences were found between treatments based on traditional cognitive behaviour therapy vs acceptance and commitment therapy. Sample size, study year, and overall risk of bias (Cochrane rating) did not consistently moderate treatment effects. Overall, the results support the use of internet-delivered cognitive and behavioural interventions as efficacious and suggest guided interventions are associated with greater clinical gains for several key pain management outcomes.


Subject(s)
Acceptance and Commitment Therapy , Chronic Pain , Adult , Chronic Pain/psychology , Chronic Pain/therapy , Cognition , Humans , Internet , Randomized Controlled Trials as Topic
6.
J Neurointerv Surg ; 14(5)2022 May.
Article in English | MEDLINE | ID: mdl-34429346

ABSTRACT

BACKGROUND: A small subset of patients with presumed idiopathic intracranial hypertension are found to have isolated internal jugular vein stenosis (IJVS). OBJECTIVE: To review the current interventions used in patients who present with intracranial hypertension secondary to IJVS. METHODS: In December 2020, we performed a literature search on Pubmed/Medline and Scopus databases for original articles studying surgical and endovascular interventions used for intracranial hypertension in the setting of internal jugular vein stenosis. No date, patient population, or study type was excluded. RESULTS: All studies that included at least one case in which a surgical or endovascular intervention was used to treat IJVS were included. Selection criteria for patients varied, most commonly defined by identification of compression of the internal jugular vein. The 17 studies included in this review ranged from case reports to large single-center cohort studies. The most used surgical intervention was styloidectomy. Styloidectomy had an overall better outcome success rate (79%) than angioplasty/stenting (66%). No complications were recorded in any of the surgical cases analyzed. Outcome measures varied, but all studies recorded clinical symptoms of the patients. CONCLUSION: Few current large cohort studies analyze surgical and endovascular interventions for patients with IJVS. Notably, the most common intervention is styloidectomy, followed by internal jugular vein stenting. By understanding the trends and experience of interventionalists and surgeons, more focused and larger studies can be performed to determine effective strategies with the best clinical outcomes.


Subject(s)
Intracranial Hypertension , Pseudotumor Cerebri , Vascular Diseases , Constriction, Pathologic/complications , Constriction, Pathologic/diagnostic imaging , Constriction, Pathologic/surgery , Humans , Intracranial Hypertension/etiology , Jugular Veins/diagnostic imaging , Jugular Veins/surgery , Pseudotumor Cerebri/complications
7.
J Vasc Interv Radiol ; 33(4): 420-426, 2022 04.
Article in English | MEDLINE | ID: mdl-34958859

ABSTRACT

PURPOSE: To compare procedure and fluoroscopy time, technical and clinical success, and costs between single-use and reusable endoscopes in patients undergoing percutaneous biliary endoscopy (PBE) with lithotripsy. MATERIAL AND METHODS: Thirty-four patients (67 procedures) were retrospectively included in the study. The patients were treated with PBE for gallstone removal from October 24, 2014, to February 12, 2020, using reusable (28 procedures) or single-use (39 procedures) endoscopes. The procedure time, fluoroscopy time, technical success rate (accessing the biliary system and locating the gallstone), clinical success rate (at least partial gallstone removal), complication rate, and cost of use were compared between the procedures. RESULTS: The mean (± standard deviation) procedure time was not significantly different between single-use (136 minutes ± 45) and reusable endoscopes (136 minutes ± 51) (P = .47). The mean fluoroscopy time was significantly shorter for single-use endoscopes (11 minutes ± 8.4) than for reusable endoscopes (18 minutes ± 12) (P = .01). When comparing single-use versus reusable endoscopes, the technical success (95% [n = 37] vs 93% [n = 26]) and the clinical success (90% [n = 35] vs 75% [n = 21]) rates were not significantly different (both, P > .05). Only 1 complication was noted in the reusable endoscope group (P = .42). The cost per case was lower for single-use ($1,500) than for reusable ($3,987) endoscope procedures, primarily due to differences in capital costs and repair costs. CONCLUSIONS: Single-use endoscopes offer the potential for lower patient radiation exposure and lower cost per case, which may reduce the financial barriers to offering PBE in interventional radiology practices. The clinical and technical success rates did not differ by endoscope type.


Subject(s)
Biliary Tract , Lithotripsy , Benchmarking , Costs and Cost Analysis , Endoscopes , Endoscopy, Gastrointestinal , Humans , Retrospective Studies
8.
J Am Heart Assoc ; 10(24): e019706, 2021 12 21.
Article in English | MEDLINE | ID: mdl-34873919

ABSTRACT

Background Caregivers provide critical support for patients with chronic diseases, including heart disease, but often experience caregiver stress that negatively impacts their health, quality of life, and patient outcomes. We aimed to inform health care teams on an evidence-based approach to supporting the caregivers of patients with heart disease. Methods and Results We conducted a systematic review and meta-analysis of randomized controlled trials written in English that evaluated interventions to support caregivers of patients with heart disease. We identified 15,561 articles as of April 2, 2020 from 6 databases; of which 20 unique randomized controlled trials were evaluated, representing a total of 1570 patients and 1776 caregivers. Most interventions focused on improving quality of life, and reducing burden, depression, and anxiety; 85% (17 of 20) of the randomized controlled trials provided psychoeducation for caregivers. Interventions had mixed results, with moderate non-significant effects observed for depression (Hedges' g=-0.64; 95% CI, -1.34 to 0.06) and burden (Hedges' g=-0.51; 95% CI, -2.71 to 1.70) at 2 to 4 months postintervention and small non-significant effects observed for quality of life and anxiety. These results were limited by the heterogeneity of outcome measures and intervention delivery methods. A qualitative synthesis of major themes of the interventions resulted in clinical recommendations represented with the acronym "CARE" (Caregiver-Centered, Active engagement, Reinforcement, Education). Conclusions This systematic review highlights the need for greater understanding of the challenges faced by caregivers and the development of guidelines to help clinicians address those challenges. More research is necessary to develop clinical interventions that consistently improve caregiver outcomes.


Subject(s)
Caregivers , Heart Diseases , Social Support , Caregivers/psychology , Heart Diseases/therapy , Humans , Randomized Controlled Trials as Topic
9.
J Investig Med ; 69(8): 1399-1403, 2021 12.
Article in English | MEDLINE | ID: mdl-34348963

ABSTRACT

Transnasal swab testing for the detection of SARS-CoV-2 is well established. The Centers for Disease Control and Prevention advocates swabbing either of the anterior nares, middle turbinate, or nasopharynx for specimen collection depending on available local resources. The purpose of this review is to investigate complications related to transnasal SARS-CoV-2 testing with specific attention to specimen collection site and swab approach. The literature demonstrates that while nasopharyngeal swabbing is associated with an increased risk of complications, it should remain the gold-standard test due to greater diagnostic accuracy relative to anterior nasal and middle turbinate swabs.


Subject(s)
COVID-19 Testing , COVID-19 , Specimen Handling/adverse effects , COVID-19 Testing/methods , Humans , Nasopharynx/virology , United States
10.
J Am Coll Radiol ; 18(12): 1668-1674, 2021 12.
Article in English | MEDLINE | ID: mdl-34418340

ABSTRACT

PURPOSE: To evaluate trends in consulting fees from industry to US-based interventional radiologists from 2014 to 2018. METHODS: Payments to interventional radiologists from January 1, 2014, to December 31, 2018, were analyzed from the CMS Open Payments Database. Payment type, total consulting fee payments per year and total payment per physician, and aggregate payments per company were analyzed before and after adjustment for outliers. RESULTS: Over the 5-year period, a total of $79.8 million was paid from industry to interventional radiologists, of which $17.6 million (22.1%) represented consulting fees. Per physician, the median total yearly amount paid as consulting fees was $5,050. Consulting fees increased from a total of $2.8 million per year in 2014 to $4.6 million per year in 2018 (+65%). After adjustment for outliers, consulting fee payments rose from $1.8 million to $3.5 million (+94%). The number of physicians paid each year increased from 156 to 219 physicians and the median payment increased from $4,327 to $5,419. Before ($5,118,966) and after adjustment, Sirtex Medical Inc paid the highest total aggregate consulting fee payments per year to self-identified interventional radiologists. After expansion to include both interventional and diagnostic radiologists by specialty type, Merck Sharp & Dohme Corp ($21,505,861) and Pfizer Inc ($11,798,255) followed by Sirtex Medical Inc ($8,276,818) paid the highest total aggregate in consulting fees. CONCLUSION: Total consulting fees to interventional radiologists increased between 2014 and 2018 by 65%, driven by both the increased number of physicians paid consulting fees and the increased average payment amount.


Subject(s)
Industry , Physicians , Databases, Factual , Fees and Charges , Humans , Radiologists , United States
12.
J Clin Neurosci ; 89: 237-242, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34119274

ABSTRACT

The SpineJack implant system was recently FDA approved for treatment of vertebral compression fractures (VCF), however United States-based outcomes data is lacking. We sought to examine the safety and clinical outcomes following vertebral augmentation using the SpineJack implant for treatment of VCF in a U.S. patient population. An IRB-approved, retrospective study of SpineJack implants used in vertebral augmentation was performed from 11/2018 to 2/2020. Outcome objectives included pain improvement, vertebral body height (VH) restoration, improvement in local kyphotic angle (LKA), and incidence of adjacent level fractures (ALF). Complications were reviewed to assess safety of the procedure. Thirty patients with VCF (60% female; mean [SD] age of 62.7 [±12.8] years) underwent a total of 53 vertebral augmentations with 106 SpineJack implants. Worst pain scores decreased significantly from 8.7 to 4.3 (95%CI of the change [Δ]: 4.3-4.4; p < 0.001). Middle and anterior VH significantly increased from 13.1 ± 0.2 to 15.9 ± 0.2 mm (95%CI Δ: 2.6-2.9 mm; p < 0.001) and 15.6 ± 0.2 to 16.8 ± 0.2 mm (95%CI Δ: 1.1-1.4 mm; p < 0.001), respectively. LKA was significantly decreased from 10.0 ± 2.1 to 7.4 ± 2.1 degrees (95%CI Δ: 2.4-2.8 degrees; p < 0.001). Four patients (13%) sustained ten ALF over a median (IQR) follow up period of 94 (17.5-203) days. There were no major adverse events during the follow up period. To summarize, vertebral augmentation with SpineJack implants of patients with VCF resulted in significantly decreased pain, restored VH, and improved LKA, without major adverse events. However, 13% of patients sustained ALF during a median follow up period of 3 months.


Subject(s)
Fractures, Compression/epidemiology , Fractures, Compression/surgery , Internal Fixators/trends , Population Surveillance , Spinal Fractures/epidemiology , Spinal Fractures/surgery , Aged , Aged, 80 and over , Female , Follow-Up Studies , Fractures, Compression/diagnostic imaging , Humans , Male , Middle Aged , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/surgery , Pain/diagnostic imaging , Pain/epidemiology , Pain/surgery , Prostheses and Implants/trends , Retrospective Studies , Spinal Fractures/diagnostic imaging , Treatment Outcome , United States/epidemiology
13.
BMC Med Educ ; 21(1): 148, 2021 Mar 06.
Article in English | MEDLINE | ID: mdl-33676520

ABSTRACT

BACKGROUND: Asian Americans (AsAm) are a rapidly growing population in the U.S. With this growing population, U.S. healthcare providers must be equipped to provide culturally competent care for AsAm patients. This project surveyed U.S. medical students on their knowledge of and attitudes towards AsAm to assess predictors of readiness to care for AsAm patients. METHOD: This cross-sectional study surveyed medical students who had completed at least one clinical rotation. The survey was distributed online to nine medical schools throughout the U.S. The survey measured self-rated knowledge of, comfort with, cultural competency (CC) towards, and explicit biases towards AsAm patients. The first three domains were analyzed in a multivariate regression model including sociodemographic characteristics and past clinical, curricular, and social experiences with AsAm. Explicit bias questions were reported descriptively. RESULTS: There were 688 respondents. Asian race, AsAm-prevalent hometown, AsAm-related extracurricular activities, Asian language knowledge, and having taken a population health course predicted increased AsAm knowledge. Social interactions with AsAm increased comfort with AsAm patients. Increasing year in medical school, more frequent exposure to AsAm patients on rotations, and prior travel to an Asian country were predictors of increased CC toward AsAm. Importantly, having completed a CC course was a significant predictor in all domains. In terms of explicit bias, students felt that AsAm patients were more compliant than Caucasian patients. Students also believed that Caucasian patients were generally more likely to receive self-perceived "preferred" versus "acceptable" care, but that in their own clinical experiences neither group received preferred care. CONCLUSION: Experience with and exposure to AsAm prior to and during medical school and CC courses may increase medical student knowledge, comfort, and CC with AsAm patients. Standardized and longitudinal CC training, increased simulations with AsAm patients, diverse student recruitment, and support for students to engage in AsAm-related activities and interact with AsAm may improve CC of future physicians towards AsAm patients and possibly other minority populations.


Subject(s)
Students, Medical , Asia , Asian , Attitude , Cross-Sectional Studies , Humans , Surveys and Questionnaires
14.
Acad Med ; 96(5): 668-670, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33369900

ABSTRACT

Morbidity and mortality conferences (MMCs) are a long-held legacy institution in academic medicine that enable medical providers and hospital administrators to learn from systemic and individual errors, thereby leading to improved medical care. Originally, this forum had 1 major role-education. The MMC evolved and a second key role was added: quality improvement. In the wake of the 2020 COVID-19 pandemic, a second evolution-one that will humanize the MMC-is required. The pandemic emphasizes the need to use MMCs not only as a place to discuss errors but also as a place for medical providers to reflect on lives lost. The authors' review of the literature regarding MMCs indicates that most studies focus on enabling MMCs to become a forum for quality improvement, while none have emphasized the need to humanize MMCs to decrease medical provider burnout and improve patient satisfaction. Permitting clinicians to be human on the job requires restructuring the MMC to provide a space for reflection and, ultimately, defining a new purpose and charge for the MMC. The authors have 3 main recommendations. First, principles of humanism such as compassion, empathy, and respect, in particular, should be incorporated into traditional MMCs. Second, shorter gatherings devoted to giving clinicians the opportunity to focus on their humanity should be arranged. Third, an MMC focused entirely on the human aspects of medical care should be periodically arranged to provide an outlet for storytelling, artistic expression, and reflection. Humanizing the MMC-a core symposium in clinical medicine worldwide-could be the first step in revitalizing the spirit at the heart of medicine, one dedicated to health and healing. This spirit, which has been eroding as the field of medicine becomes increasingly corporate in structure and mission, is as essential during peaceful times in health care as during a pandemic.


Subject(s)
Congresses as Topic/organization & administration , Hospital Administration/standards , Humanism , Quality Improvement , Burnout, Professional/prevention & control , COVID-19 , Hospital Mortality , Humans , Morbidity , Pandemics , Patient Satisfaction , SARS-CoV-2
15.
MedComm (2020) ; 1(3): 328-337, 2020 Dec.
Article in English | MEDLINE | ID: mdl-34308416

ABSTRACT

Bcl-xL, an antiapoptotic protein, is frequently overexpressed in cancer to promote survival of tumor cells. However, we have previously shown that Bcl-xL promotes migration, invasion, and metastasis independent of its antiapoptotic function in mitochondria. The pro-metastatic function of Bcl-xL may require its translocation into the nucleus. Besides overexpression, patient-associated mutations of Bcl-xL have been identified in large-scale cancer genomics projects. Understanding the functions of these mutations will guide the development of precision medicine. Here, we selected four patient-associated Bcl-xL mutations, R132W, N136K, R165W, and A201T, to investigate their impacts on antiapoptosis, migration, and nuclear translocation. We found that all four mutation proteins could be detected in both the nucleus and cytosol. Although all four mutations disrupted the antiapoptosis function, one of these mutants, N136K, significantly improved the ability to promote cell migration. These data suggest the importance of developing novel Bcl-xL inhibitors to ablate both antiapoptotic and pro-metastatic functions of Bcl-xL in cancer.

16.
Mol Cancer ; 18(1): 92, 2019 05 09.
Article in English | MEDLINE | ID: mdl-31072393

ABSTRACT

The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers. We previously screened genes upregulated in human hepatocellular carcinomas for their metastatic function in a mouse model of pancreatic neuroendocrine tumor (PNET) and identified that human RHAMMB promoted liver metastasis. It was unknown whether RHAMMB is upregulated in pancreatic cancer or contributes to its progression. In this study, we found that RHAMM protein was frequently upregulated in human PNETs. We investigated alternative splicing isoforms, RHAMMA and RHAMMB, by RNA-Seq analysis of primary PNETs and liver metastases. RHAMMB, but not RHAMMA, was significantly upregulated in liver metastases. RHAMMB was crucial for in vivo metastatic capacity of mouse and human PNETs. RHAMMA, carrying an extra 15-amino acid-stretch, did not promote metastasis in spontaneous and experimental metastasis mouse models. Moreover, RHAMMB was substantially higher than RHAMMA in pancreatic ductal adenocarcinoma (PDAC). RHAMMB, but not RHAMMA, correlated with both higher EGFR expression and poorer survival of PDAC patients. Knockdown of EGFR abolished RHAMMB-driven PNET metastasis. Altogether, our findings suggest a clinically relevant function of RHAMMB, but not RHAMMA, in promoting PNET metastasis in part through EGFR signaling. RHAMMB can thus serve as a prognostic factor for pancreatic cancer.


Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Extracellular Matrix Proteins/genetics , Hyaluronan Receptors/genetics , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/pathology , Up-Regulation , Alternative Splicing , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Cell Line, Tumor , Disease Progression , ErbB Receptors/metabolism , Extracellular Matrix Proteins/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Hyaluronan Receptors/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Male , Mice , Neoplasm Transplantation , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Prognosis , Signal Transduction , Survival Analysis
17.
Neoplasia ; 18(10): 610-617, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27664376

ABSTRACT

In human studies and mouse models, the contributions of p53 and p16Ink4a/p19Arf loss are well established in pancreatic ductal adenocarcinoma (PDAC). Although loss of functional p53 pathway and loss of Ink4a/Arf in human pancreatic acinar cell carcinoma (PACC) and pancreatic neuroendocrine tumor (PanNET) are identified, their direct roles in tumorigenesis of PACC and PanNET remain to be determined. Using transgenic mouse models expressing the viral oncogene polyoma middle T antigen (PyMT), we demonstrate that p53 loss in pancreatic Pdx1+ progenitor cells results in aggressive PACC, whereas Ink4a/Arf loss results in PanNETs. Concurrent loss of p53 and Ink4a/Arf resembles loss of p53 alone, suggesting that Ink4a/Arf loss has no additive effect to PACC progression. Our results show that specific tumor suppressor genotypes provocatively influence the tumor biological phenotypes in pancreatic progenitor cells. Additionally, in a mouse model of ß-cell hyperplasia, we demonstrate that p53 and Ink4a/Arf play cooperative roles in constraining the progression of PanNETs.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p16/deficiency , Cyclin-Dependent Kinase Inhibitor p19/deficiency , Neoplastic Stem Cells/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Tumor Suppressor Protein p53/deficiency , Animals , Cell Transformation, Neoplastic/genetics , Disease Models, Animal , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Mice , Mice, Transgenic , Neoplasm Metastasis , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/mortality , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/mortality , Phenotype , Prognosis , Tumor Burden
18.
J Clin Nurs ; 20(9-10): 1319-28, 2011 May.
Article in English | MEDLINE | ID: mdl-21492278

ABSTRACT

AIM: To identify omissions in hand hygiene practice and glove use among hospital workers in Hong Kong. BACKGROUND: Hospital-acquired infection is the commonest complication affecting hospitalised patients. Even though research evidence suggests that hand hygiene and proper glove use are the most important ways to prevent the spread of disease and infection, compliance with both are reported to be unacceptably low. DESIGN: An observational study of hospital workers in one acute and two convalescence and rehabilitation hospitals in Hong Kong was conducted. The participating clinical areas included the medical and surgical wards, accident and emergency department and intensive care unit. METHODS: Hand hygiene practice and glove use amongst 206 hospital health and support workers, stratified according to years of working experience, were observed. RESULTS: The number of observed episodes for hand hygiene was 1037 and for glove use 304. Compliance with hand hygiene was 74.7% and with glove use 72.4%. In approximately two-third of episodes, participants washed their hands after each patient contact; though, 78.5% failed to rub their hands together vigorously for at least 15 seconds. The major break in compliance with glove use was failure to change gloves between procedures on the same patient. In 28.6% of observed glove use episodes, participants did not wear gloves during procedures that exposed them to blood, body fluids, excretion, non-intact skin or mucous membranes. Significant differences in performance scores on antiseptic hand rub were found between the two types of hospital and on glove use between the three groups of work experience: ≤ 5, 6-10, >10 years. RELEVANCE TO CLINICAL PRACTICE: Education and reinforcement of proper hand hygiene practice and glove use among hospital health and support workers is needed.


Subject(s)
Cross Infection/prevention & control , Gloves, Protective , Hand Disinfection , Hospitals , Female , Hong Kong , Humans , Infection Control , Male
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