Publications by authors named "Anna Lee"

407 Publications

Resilience in Multicultural Families of Children With Disabilities in Korea: A Path Analysis Using National Data.

J Nurs Scholarsh 2021 Apr 7. Epub 2021 Apr 7.

Research professor, College of Nursing, Korea University, Seoul, Korea.

Purpose: The number of multicultural families has increased globally, and Korea has also witnessed a surge. Along with the various challenges experienced by these families, a child with a disability can pose additional challenges. In-depth knowledge about resilience factors among multicultural families of children with disabilities is important. The aim of this study was to examine relationships between family demands, family appraisals, family problem solving and coping, family resources, and family adaptation in multicultural families of children with disabilities in Korea as perceived by married immigrants.

Design: This study was based on a secondary analysis of national survey data in 2015 and 2018 in Korea.

Methods: A total of 256 multicultural families who have children with disabilities participated. Family demands were identified by examining marital conflict, cultural differences, marital status, and public assistance recipient households. Family appraisal was assessed by how the family perceived the married immigrant's culture. Family problem solving and coping were examined by how actively a married immigrant participated in social activities. Family resources were assessed by examining Korean language competency and the health status of immigrants. Family adaptation was identified by how immigrants perceived their life satisfaction. Path analysis was used to assess the factors.

Findings: Family demands had a direct impact on family resources and family adaptation. Family appraisal had a direct impact on family adaptation. Family resources mediated the effect of family demands on family adaptation.

Conclusions: This study demonstrated that although a multicultural family of a child with a disability struggles with family demands, if the family receives positive resources from family members, they can adapt well. Current findings can be used to develop interventions that can foster greater resilience among families.

Clinical Relevance: This study provides evidence that nurses can target modifiable family aspects, including immigrants' health and family perceptions of immigrants' cultures identified in this study to enhance the immigrant and family adaptation.
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http://dx.doi.org/10.1111/jnu.12658DOI Listing
April 2021

Relative survival in adults with new delirium, cerebrovascular events or both after cardiac surgery: A prospective cohort study.

Eur J Anaesthesiol 2021 05;38(5):558-560

From the Department of Anaesthesia and Intensive Care (AL, DKWY, FFN, GMJ) and Division of Cardiothoracic Surgery, Department of Surgery (MJU), The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, China.

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http://dx.doi.org/10.1097/EJA.0000000000001241DOI Listing
May 2021

Granulocyte Colony Stimulating Factor Expression in Breast Cancer and Its Association with Carbonic Anhydrase IX and Immune Checkpoints.

Cancers (Basel) 2021 Mar 1;13(5). Epub 2021 Mar 1.

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.

Purpose: Granulocyte colony-stimulating factor (G-CSF) and hypoxia modulate the tumour immune microenvironment. In model systems, hypoxia-induced carbonic anhydrase IX (CAIX) has been associated with G-CSF and immune responses, including M2 polarization of macrophages. We investigated whether these associations exist in human breast cancer specimens, their relation to breast cancer subtypes, and clinical outcome.

Methods: Using validated protocols and prespecified scoring methodology, G-CSF expression on carcinoma cells and CD163 expression on tumour-associated macrophages were assayed by immunohistochemistry and applied to a tissue microarray series of 2960 primary excision specimens linked to clinicopathologic, biomarker, and outcome data.

Results: G-CSF expression showed a significant positive association with ER negativity, HER2 positivity, presence of CD163+ M2 macrophages, and CAIX expression. In univariate analysis, G-CSF phenotype was associated with improved survival in non-luminal cases, although the CAIX+ subset had a significantly adverse prognosis. A significant positive association was observed between immune checkpoint biomarkers on tumour-infiltrating lymphocytes and both G-CSF- and CAIX-expressing carcinoma cells. Immune checkpoint biomarkers correlated significantly with favourable prognosis in G-CSF/non-luminal cases independent of standard clinicopathological features.

Conclusions: The prognostic associations linking G-CSF to immune biomarkers and CAIX strongly support their immunomodulatory roles in the tumour microenvironment.
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http://dx.doi.org/10.3390/cancers13051022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957699PMC
March 2021

Differential Impact of Inhibitory G-Protein Signaling Pathways in Ventral Tegmental Area Dopamine Neurons on Behavioral Sensitivity to Cocaine and Morphine.

eNeuro 2021 Mar-Apr;8(2). Epub 2021 Mar 26.

Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455

Drugs of abuse engage overlapping but distinct molecular and cellular mechanisms to enhance dopamine (DA) signaling in the mesocorticolimbic circuitry. DA neurons of the ventral tegmental area (VTA) are key substrates of drugs of abuse and have been implicated in addiction-related behaviors. Enhanced VTA DA neurotransmission evoked by drugs of abuse can engage inhibitory G-protein-dependent feedback pathways, mediated by GABA receptors (GABARs) and D DA receptors (DRs). Chemogenetic inhibition of VTA DA neurons potently suppressed baseline motor activity, as well as the motor-stimulatory effect of cocaine and morphine, confirming the critical influence of VTA DA neurons and inhibitory G-protein signaling in these neurons on this addiction-related behavior. To resolve the relative influence of GABAR-dependent and DR-dependent signaling pathways in VTA DA neurons on behavioral sensitivity to drugs of abuse, we developed a neuron-specific viral CRISPR/Cas9 approach to ablate DR and GABAR in VTA DA neurons. Ablation of GABAR or DR did not impact baseline physiological properties or excitability of VTA DA neurons, but it did preclude the direct somatodendritic inhibitory influence of GABAR or DR activation. DR ablation potentiated the motor-stimulatory effect of cocaine in male and female mice, whereas GABAR ablation selectively potentiated cocaine-induced activity in male subjects only. Neither DR nor GABAR ablation impacted morphine-induced motor activity. Collectively, our data show that cocaine and morphine differ in the extent to which they engage inhibitory G-protein-dependent feedback pathways in VTA DA neurons and highlight key sex differences that may impact susceptibility to various facets of addiction.
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http://dx.doi.org/10.1523/ENEURO.0081-21.2021DOI Listing
March 2021

Diffuse alveolar haemorrhage in a child with trisomy 21.

J Paediatr Child Health 2021 Mar 10. Epub 2021 Mar 10.

Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.

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http://dx.doi.org/10.1111/jpc.15331DOI Listing
March 2021

B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies.

Cell Host Microbe 2021 04 3;29(4):564-578.e9. Epub 2021 Mar 3.

U.S. Military HIV Research Program, Center of Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA. Electronic address:

Determining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14-43 days of viremia that predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV envelope (Env) within 1 month of initial viremia. A higher frequency of founder-Env-specific naive B cells was associated with increased B cell activation and differentiation and predictive of bNAb development. These data demonstrate that the initial B cell interaction with the founder HIV Env is important for the development of broadly neutralizing antibodies and provide evidence that events within HIV acute infection lead to downstream functional outcomes.
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http://dx.doi.org/10.1016/j.chom.2021.01.016DOI Listing
April 2021

Cytokines associated with hemorrhage in proliferative diabetic retinopathy.

Int Ophthalmol 2021 May 20;41(5):1845-1853. Epub 2021 Feb 20.

Department of Ophthalmology, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, #327 Sosa-ro, Wonmi-gu, Bucheon, Gyeonggi-do, 14647, Republic of Korea.

Purpose: To investigate aqueous cytokine levels in association with hemorrhage in proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus.

Methods: Sixty-six eyes with treatment-naïve PDR, including 26 hemorrhagic and 40 nonhemorrhagic eyes were included in this institutional study. Aqueous humor levels of interleukin (IL)-1b, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and soluble VEGF receptor-1 were obtained by multiplex bead assay. Visual acuity and hemorrhage area measurements were obtained, and correlations between cytokine levels and hemorrhage were identified.

Results: Levels of MCP-1, TNF-α, and VEGF were higher in hemorrhagic eyes (1506.77 vs. 2131.31 pg/mL, 0.43 vs. 0.63 pg/mL, and 103.96 vs. 206.96 pg/mL; P = 0.050, 0.022, and 0.027, respectively). The levels of IL-8, MCP-1, TNF-α, and VEGF showed positive correlation with visual acuity (P = 0.019, 0.015, 0.001, and 0.014, respectively). The hemorrhage area revealed positive correlation with TNF-α and VEGF levels (P = 0.001 and < 0.001, respectively).

Conclusion: The presence and amount of hemorrhage in PDR were associated not only with VEGF concentration, but also with the levels of certain inflammatory cytokines, suggesting a role of both VEGF and inflammation in hemorrhagic eyes.
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http://dx.doi.org/10.1007/s10792-021-01746-9DOI Listing
May 2021

Outcomes and prognostic factors of major salivary gland tumors treated with proton beam radiation therapy.

Head Neck 2021 Apr 19;43(4):1056-1062. Epub 2021 Feb 19.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York City, USA.

Background: Proton beam radiation therapy (PBRT) has dosimetric advantages compared to photon radiation therapy for the treatment of major salivary gland tumors (MSGTs).

Methods: Patients with non-metastatic MSGTs treated at a single proton therapy center from October 2013 to October 2018 were retrospectively reviewed.

Results: Sixty-eight patients with MSGTs were included and the most common site and histology were the parotid gland (75.0%) and adenoid cystic carcinoma (22.1%), respectively. The 3-year rates of locoregional control, progression-free survival, and overall survival were 95.1% (95% CI: 89.9%-100.0%), 80.7% (70.2%-92.7%), and 96.1% (95% CI: 90.9%-100.0%), respectively.

Conclusion: In a large cohort of MSGTs treated with PBRT, the rates of locoregional control were high in short-term follow-up and treatment was well tolerated.
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http://dx.doi.org/10.1002/hed.26563DOI Listing
April 2021

Socioeconomic inequality and omission of adjuvant radiation therapy in high-risk, early-stage endometrial cancer.

Gynecol Oncol 2021 May 15;161(2):463-469. Epub 2021 Feb 15.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, NY, New York 10065, United States of America. Electronic address:

Objective: Gaps in access to appropriate cancer care, and associated cancer mortality, have widened across socioeconomic groups. We examined whether demographic and socioeconomic factors influenced receipt of adjuvant radiation therapy (RT) in patients with high-risk, early-stage endometrial cancer.

Methods: A retrospective study cohort was selected from 349,404 endometrial carcinoma patients from the National Cancer Database in whom adjuvant RT would be recommended per national guidelines. The study included surgically treated patients with endometrioid endometrial cancer with one of the following criteria: 1) FIGO 2009 stage IB, grade 1/2 disease, age ≥ 60 years; 2) stage IB, grade 3 disease; or 3) stage II disease. Logistic regression analysis was performed to identify factors associated with omission of adjuvant RT. Association between adjuvant RT, covariables, and overall survival (OS) was assessed with multivariable Cox proportional hazards models.

Results: 19,594 patients were eligible for analysis; 47% did not receive adjuvant RT. Omission of adjuvant RT was more prevalent among African-American, Hispanic, and Asian compared to non-Hispanic white patients (OR 0.79, 95%CI: 0.69-0.91; OR 0.75, 95%CI: 0.64-0.87; OR 0.75, 95%CI: 0.60-0.94, respectively). Lower median household income of patient's area of residence, lack of health insurance, treatment at non-academic hospitals, farther distance to treatment facilities, and residence in metropolitan counties were associated with omission of adjuvant RT. Such omission was independently associated with worse OS (HR1.43, p < 0.001).

Conclusion: Adjuvant RT is omitted in 47% of patients with early-stage, high-risk endometrial cancer, which is associated with poor access to appropriate, high-quality care and worse outcome.
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http://dx.doi.org/10.1016/j.ygyno.2021.01.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084986PMC
May 2021

Any day, split halfway: Flexibility in scheduling high-dose cisplatin-A large retrospective review from a high-volume cancer center.

Int J Cancer 2021 Feb 14. Epub 2021 Feb 14.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m  × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization-a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m  × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow-up was 8.0 years (1.8 months-17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus-HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates.
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http://dx.doi.org/10.1002/ijc.33518DOI Listing
February 2021

Protocol for the determination of intracellular phase separation thresholds.

STAR Protoc 2021 Mar 1;2(1):100308. Epub 2021 Feb 1.

Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

To date, phase separation studies have largely been limited to assays using non-native conditions and aggregation-prone recombinant proteins that are often difficult to purify. This protocol describes the determination of relative protein concentration thresholds for phase separation through fluorescent imaging of GFP-tagged proteins in cells. The commercial availability of various plasmids and antibodies, as well as advances in gene editing, allow this procedure to be modified for the study of various phase-separating proteins in their relevant contexts. For complete details on the use and execution of this protocol, please refer to Lee et al. (2020).
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http://dx.doi.org/10.1016/j.xpro.2021.100308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856470PMC
March 2021

Family Variables and Quality of Life in Children with Down Syndrome: A Scoping Review.

Int J Environ Res Public Health 2021 01 7;18(2). Epub 2021 Jan 7.

School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7460, USA.

The purpose of this scoping review was to identify the family and child quality of life variables that have been studied in relation to one another in children with Down syndrome, the frequency with which different relationships have been studied, and the extent to which family variables were the focus of the research aims. A literature search was conducted to find studies published between January 2007 and June 2018. The initial search yielded 2314 studies; of these, 43 were selected for a final review. Researchers most often addressed family resources and family problem-solving and coping concerning child personal development and physical well-being. Little attention to child emotional well-being was observed, with none considering family appraisal of child emotional well-being. The relationship between family variables and child QoL rarely was the primary focus of the study. Methodologically, most reviewed studies used cross-sectional designs, were conducted in North America and based on maternal report. From future research considering the issues found in this review, healthcare providers can obtain an in-depth understanding of relationships between children and family variables.
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http://dx.doi.org/10.3390/ijerph18020419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825751PMC
January 2021

Design, synthesis and anti-inflammatory activity of imidazol-5-yl pyridine derivatives as p38α/MAPK14 inhibitor.

Bioorg Med Chem 2021 Feb 28;31:115969. Epub 2020 Dec 28.

Center for Biomaterials, Korea Institute of Science & Technology (KIST School), Seoul, Seongbuk-gu, 02792, Republic of Korea; University of Science & Technology (UST), Daejeon, Yuseong-gu, 34113, Republic of Korea. Electronic address:

P38α/MAPK14 is intracellular signalling regulator involved in biosynthesis of inflammatory mediator cytokines (TNF-α, IL-1, IL-6, and IL-1b), which induce the production of inflammatory proteins (iNOS, NF-kB, and COX-2). In this study, drug repurposing strategies were followed to repositioning of a series of B-RAF imidazol-5-yl pyridine inhibitors to inhibit P38α kinase. A group 25 reported P38α kinase inhibitors were used to build a pharmacophore model for mapping the target compounds and proving their affinity for binding in P38α active site. Target compounds were evaluated for their potency against P38α kinase, compounds 11a and 11d were the most potent inhibitors (IC = 47 nM and 45 nM, respectively). In addition, compound 11d effectively inhibited the production of proinflammatory cytokinesTNF-α, 1L-6, and 1L-1β in LPS-induced RAW 264.7 macrophages with IC values of 78.03 nM, 17.6 µM and 82.15 nM, respectively. The target compounds were tested for their anti-inflammatory activity by detecting the reduction of Nitric oxide (NO) and prostaglandin (PGE2) production in LPS-stimulated RAW 264.7 macrophages. Compound 11d exhibited satisfied inhibitory activity of the production of PGE2 and NO with IC values of 0.29 µM and 0.61 µM, respectively. Molecular dynamics simulations of the most potent inhibitor 11d were carried out to illustrate its conformational stability in the binding site of P38α kinase.
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http://dx.doi.org/10.1016/j.bmc.2020.115969DOI Listing
February 2021

Bird feathers are potential biomonitors for airborne elemental carbon.

Environ Monit Assess 2021 Jan 6;193(1):35. Epub 2021 Jan 6.

Department of Biological Sciences, University of North Texas, 1155 Union Circle #310559, Denton, TX, USA.

Birds can serve as effective biomonitors of air pollution, yet few studies have quantified external particulate matter accumulation on bird feathers. Biomonitoring of airborne elemental carbon (EC) is of critical significance because EC is a component of particulate matter with adverse effects on air quality and human health. To assess their effectiveness for use in EC monitoring, we compared EC accumulation on bird feathers at two sites that differed in vehicular traffic volume in an urban environment within the Dallas-Fort Worth Metropolitan Area, USA. Moulted flight feathers from domestic chickens were experimentally exposed to ambient EC pollution for 5 days in two urban microenvironments 1.5 km distant from each other that differed in traffic volume--adjacent to an interstate highway and a university campus bus stop. Feathers near the highway accumulated approximately eight times more EC (307 ± 34 μg m day), on average, than feathers near the bus stop (40 ± 9 μg m day). These findings indicate that EC accumulation on feathers varies over short distances within urban areas and that bird feathers potentially can be used for biomonitoring airborne EC.
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http://dx.doi.org/10.1007/s10661-020-08804-2DOI Listing
January 2021

Impact of obesity on safety outcomes and treatment modifications with ado-trastuzumab emtansine in breast cancer patients.

J Oncol Pharm Pract 2020 Dec 26:1078155220982648. Epub 2020 Dec 26.

Department of Pharmacy, Atrium Health, Levine Cancer Institute, Concord, NC, USA.

Introduction: Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate indicated for the treatment of HER2-positive breast cancer. The 2012 American Society of Clinical Oncology guidelines on chemotherapy dosing in obesity recommend using full weight-based cytotoxic chemotherapy doses to treat obese patients with cancer. These guidelines were published prior to the advent of anticancer antibody-drug conjugates. There is a need to investigate the safety of T-DM1 in obese patients.

Methods: This retrospective chart review included adult patients with breast cancer receiving T-DM1. The primary endpoint was a composite of the incidence of T-DM1 treatment modifications secondary to an adverse event. Secondary outcomes included the incidence of dose reductions, dose delays, treatment discontinuations, and adverse events.

Results: A total of 119 patients with HER2-positive breast cancer who received T-DM1 therapy were included in this study: 44 obese patients and 75 non-obese patients. The composite outcome of treatment modifications due to toxicity was significantly higher in obese patients compared to non-obese patients (45% vs 25%, p = 0.024). Treatment delays were significantly higher in obese patients (36% vs 16%, p = 0.011). All-grade adverse events with a higher incidence in obese patients included left ventricular ejection fraction decrease (11% vs 5%), bilirubin increase (32% vs 12%), thrombocytopenia (61% vs 55%), and peripheral neuropathy (34% vs 27%).

Conclusions: This study suggests obese patients receiving T-DM1 may require more treatment modifications secondary to adverse events compared to non-obese patients. Larger studies are needed to determine if obese patients are at higher risk for specific T-DM1-induced adverse events.
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http://dx.doi.org/10.1177/1078155220982648DOI Listing
December 2020

Treatment Deescalation Strategies for Nasopharyngeal Cancer: A Review.

JAMA Oncol 2020 Dec 23. Epub 2020 Dec 23.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: Since the advent of modern radiotherapy techniques and incorporation of systemic chemotherapy for nasopharyngeal cancer, locoregional control has been excellent. However, the rate of treatment-related complications, many of which are irreversible, remains high. New approaches are being explored to determine whether the toxic effects of treatment can be relieved while maintaining disease control. This review presents the current state of deescalation strategies for nasopharyngeal cancer.

Observations: A review of the literature shows that deescalation approaches can be generally categorized into deescalating systemic therapy vs deescalating radiotherapy. This review discusses studies that have explored sparing chemotherapy in selected patients with stage II cancer as well as altering the chemotherapy scheduling, dosing, and agent from the current standard of care, cisplatin. Deescalating radiotherapy has involved decreasing the dose and the treatment volume. In many cases, these approaches are being guided by measuring Epstein-Barr virus DNA levels, which is a robust biomarker for screening, treatment monitoring, and surveillance. Ongoing work with various imaging modalities, such as fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced or diffusion-weighted magnetic resonance imaging sequences, have shown promise as another biomarker to safely guide practitioners toward deescalation.

Conclusions And Relevance: Various strategies to deescalate treatment in nasopharyngeal cancer have been explored, and outcomes have remained excellent in most approaches. Patient selection remains key, and long-term outcomes and late complications are still to be determined. Continued investigation with prospective, multi-institutional studies are needed to better elucidate how treatment for nasopharyngeal carcinoma can best be individualized and deescalated.
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http://dx.doi.org/10.1001/jamaoncol.2020.6154DOI Listing
December 2020

Relationship Between Retinal Capillary Nonperfusion Area and Renal Function in Patients With Type 2 Diabetes.

Invest Ophthalmol Vis Sci 2020 12;61(14):14

Department of Ophthalmology, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea.

Purpose: We sought to assess the relationship between retinal nonperfusion area (NPA) on ultra-widefield fluorescein angiography (UWFA) and renal function in type 2 diabetes mellitus (DM) patients with diabetic retinopathy (DR) and nephropathy.

Methods: UWFA was performed in 248 eyes (124 patients) with DR, comprising 94 eyes from patients with chronic kidney disease (CKD) caused by diabetes and 154 eyes without CKD (non-CKD). Serum creatinine level (Cr), estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio (UACR), and urine protein/creatinine ratio (UPCR) were collected. On UWFA, retinal NPA was measured in an automated manner. The correlation between NPA and renal function was analyzed.

Results: The mean NPA value of the total eye was 33.11 ± 45.77-disc diameter (DA) in non-CKD and 100.57 ± 69.52 in CKD (P < 0.001). NPA of posterior pole was 1.21 ± 3.28 DA in non-CKD and 7.99 ± 6.75 in CKD group (P < 0.001). The NPA values of both the total eye and posterior pole were significantly correlated with Cr (r = 0.585 and 0.483), eGFR (r = -0.572 and -0.524), UACR (r = 0.541 and 0.482), and UPCR (r = 0.509 and 0.529, respectively) (all P ≤ 0.001). Linear modeling encompassing all clinical factors and relative clinical factors suggested eGFR as the most important predictor for NPAs of the total eye and posterior pole.

Conclusions: Larger retinal NPA on UWFA is associated with worse renal function in DM patients. Renal function can be used to predict retinal NPA in type 2 DM patients with nephropathy and DR.
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http://dx.doi.org/10.1167/iovs.61.14.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735947PMC
December 2020

RV144 HIV-1 vaccination impacts post-infection antibody responses.

PLoS Pathog 2020 12 8;16(12):e1009101. Epub 2020 Dec 8.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.

The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Ab-dependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection.
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http://dx.doi.org/10.1371/journal.ppat.1009101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748270PMC
December 2020

Mechanical Ventilation Discontinuation Practices in Asia: A Multinational Survey.

Ann Am Thorac Soc 2020 Dec 7. Epub 2020 Dec 7.

The Chinese University of Hong Kong, Dept of Anaesthesia & Intensive Care, Shatin, Hong Kong;

Rationale: There are limited data on mechanical discontinuation practices in Asia.

Objectives: To document self-reported mechanical discontinuation practices and determine whether there is clinical equipoise regarding protocolized weaning amongst Asian Intensive Care specialists.

Methods: Survey using a validated questionnaire, distributed using a snowball method to Asian Intensive Care specialists.

Results: Of 2,967 invited specialists from 20 territories, 2,074 (69.9%) took part. 60.5% were from China. 42% of all respondents worked in Intensive Care units where respiratory therapists were present. 78.9% used a spontaneous breathing trial as the initial weaning step. 44.3% frequently-always used pressure support alone, 53.4% intermittent spontaneous breathing trials with pressure support in between and 19.8% synchronized intermittent mandatory ventilation with pressure support as a weaning mode. 56.3% routinely stopped feeds before extubation. 71.5% generally followed a sedation protocol or guideline. 61.8% worked in an Intensive Care unit with a weaning protocol. Of these 78.2% frequently-always followed the protocol. Multivariate analysis involving a modified Poisson regression analysis showed that working in an Intensive Care unit with a weaning protocol and frequently-always following it was positively associated with upper-middle income territory, university affiliated hospital, or in an Intensive Care unit that employed respiratory therapists; and negatively with low-income or low-middle income territory or a public hospital. There was no significant association with "in house" intensivist at night, multidisciplinary Intensive Care unit, closed Intensive Care unit or nurse-patient ratio. There was heterogenity in agreement/disagreement with the statement "evidence clearly supports protocolized weaning over non-protocolized weaning".

Conclusions: A substantial minority of Asian Intensive Care specialists do not wean patients in accordance with best available evidence or current guidelines. There is clinical equipoise regarding the benefit of protocolized weaning.
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http://dx.doi.org/10.1513/AnnalsATS.202008-968OCDOI Listing
December 2020

Parking Costs-A Family Affair-Reply.

JAMA Oncol 2021 Feb;7(2):307

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

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http://dx.doi.org/10.1001/jamaoncol.2020.6368DOI Listing
February 2021

Multimedia resources to support the recruitment of committed hematopoietic stem cell donors: Perspectives of the most-needed donors.

Transfusion 2021 Jan 2;61(1):274-285. Epub 2020 Dec 2.

Stem Cell Club, Toronto, Ontario, Canada.

Background: Recruitment of committed unrelated hematopoietic stem cell donors from the most-needed demographics remains a challenge for donor recruitment organizations worldwide. Multimedia resources are gaining attention as a modality to support recruitment efforts; however, there is a lack of guidance for the development of such tools. This qualitative study explores the perspectives of eligible stem cell donors on an educational whiteboard video about stem cell donation, generating insights into how whiteboard videos and related multimedia may be optimized for donor recruitment.

Study Design And Methods: Eight semistructured focus groups were conducted with 38 potential donors from the most-needed demographics (young, male, and non-Caucasian) after they had watched a 3.5-minute whiteboard video explaining key concepts in stem cell donation (https://youtu.be/V4fVBtxnWfM). Constructivist grounded theory was used to identify themes and to develop a framework for understanding participants' preferred features of recruitment multimedia.

Results: Participants identified a range of features contributing to the effectiveness of recruitment multimedia, adding that the whiteboard video is an effective, integrated, and readily accessible format for supporting donor recruitment. Topics that participants felt are important to address include knowledge gaps regarding donation procedures, concerns about donor safety, and the particular need for specific donor demographics. Suggested avenues for improvement include the addition of donor/recipient/patient personal experiences, attention-grabbing hooks, and a call to action including opportunities for further learning.

Conclusions: Several considerations were generated to inform the development of future multimedia for donor education/recruitment and are relevant to donor recruitment organizations worldwide.
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http://dx.doi.org/10.1111/trf.16186DOI Listing
January 2021

Patterns of Care and Outcomes of Low-Lying Adenocarcinoma and Squamous Cell Carcinoma of the Rectum.

J Gastrointest Cancer 2020 Nov 19. Epub 2020 Nov 19.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: Squamous cell carcinoma (SCC) of the rectum is a unique entity that lacks definitive guidelines regarding prognosis and treatment. This study aimed to analyze patterns of care and survival for SCC and adenocarcinoma (AC) of the rectum.

Methods: This was a retrospective analysis of patients with stage I-III SCC or AC of the rectum treated from 2004 to 2016 from the National Cancer Database. The treatment groups analyzed were surgery alone (S), chemoradiation followed by surgery (CRT + S), surgery followed by chemoradiation (S + CRT), and definitive chemoradiation (CRT). Patient- and clinical-related factors were compared. Overall survival was assessed with the Kaplan-Meier method and Cox proportional regression models.

Results: Of the patients studied, 21,587 (97.1%) were AC and 640 (2.9%) were SCC. Among patients with AC, most (n = 8549, 59.4%) received chemoradiation followed by surgery; those with SCC (n = 305, 66.4%) received definitive chemoradiation. Among patients who received surgery, the majority (69.2%) with AC histology had a low anterior resection while the majority (52.1%) of SCC had an abdominoperineal resection. Five-year overall survival of AC versus SCC in the entire cohort was 61.6% versus 56.1%, respectively (p < 0.001). On multivariable analysis for AC, CRT + S (HR 0.61, p < 0.001), or S + CRT (HR 0.67, p < 0.001) had improved survival compared to S alone while those who had definitive CRT (HR 1.55, p < 0.001) had worse survival.

Conclusions: SCC of the rectum tends to be treated like anal cancers with definitive chemoradiation, with similar survival to historical reports of anal cancer. AC of the rectum is most commonly treated under the rectal cancer paradigm.
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http://dx.doi.org/10.1007/s12029-020-00552-3DOI Listing
November 2020

Patterns of Care and Survival of Metastatic Metaplastic Breast Cancer Patients.

Cureus 2020 Sep 9;12(9):e10339. Epub 2020 Sep 9.

Radiation Oncology, Summit Medical Group, Berkeley Heights, USA.

Background: Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer, usually triple negative disease and chemotherapy refractory. Despite this, the standard of care remains the same as invasive ductal breast cancer. We sought to analyze patterns of care and outcomes among patients with metastatic MBC.

Methods: Patients over 18 years diagnosed with metastatic MBC from 2004-2015 were identified in the National Cancer Database (NCDB). Clinical and demographic details were compared between two groups (chemotherapy vs no chemotherapy). Logistic regression was performed to assess for predictors of receiving chemotherapy. The Kaplan-Meier method was used to assess overall survival (OS) and Cox regression analysis was used to assess the impact of covariates on OS.

Results: There were 7,580 patients with MBC of which 417 (5.5%) presented with metastatic disease. Median age was 65 years (interquartile range (IQR) 54-76) and median follow up for living patients was 48 months (IQR 31-77). One hundred and fifty-six (37.4%) patients received chemotherapy. On multivariable logistic regression analyses, treatment at an academic facility was associated with an increased likelihood of receiving chemotherapy (OR 3.14, 95% CI 1.95-5.03, p<0.001) while age ≥65 years (OR 0.54, 95% CI 0.34-0.86, p=0.009) and receipt of hormonal therapy (OR 0.35, 95% CI 0.15-0.85, p=0.021) were associated with a decreased likelihood of receiving chemotherapy. On multivariable Cox regression analysis, higher Charlson-Deyo score (hazard ratio (HR) 1.35-1.78, p<0.05) was associated with worse survival while receipt of chemotherapy (HR 0.76, 95% CI 0.59-0.99, p=0.041) and having insurance (HR 0.34-0.47, p<0.05) were associated with improved survival. Patients who received chemotherapy had improved median (twelve versus eight months), one-year (51% versus 38%), and two-year (35% versus 21%) OS, as compared to those who did not receive chemotherapy (p=0.006).  Conclusions: In this study of MBC patients, there was a survival benefit with palliative chemotherapy in the setting of metastatic disease. As expected, treatment was most often given to younger patients.
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http://dx.doi.org/10.7759/cureus.10339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605212PMC
September 2020

Brief compression-only cardiopulmonary resuscitation and automated external defibrillator course for secondary school students: a multischool feasibility study.

BMJ Open 2020 10 21;10(10):e040469. Epub 2020 Oct 21.

Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China

Objectives: This study assessed the feasibility and preliminary efficacy of a 2-hour compression-only cardiopulmonary resuscitation and automated external defibrillator (CO-CPRAED) course in secondary school students.

Design: Prospective pre-post feasibility study.

Setting And Participants: 128 students (12-15 years old) without prior basic life support (BLS) training at four secondary schools in Hong Kong. All students were followed up at 3 months after training.

Interventions: Emergency medicine-trained nurse and physicians taught the 2-hour CO-CPRAED course using the American Heart Association 'CPR in School Training Kit' programme. Students were trained in groups up to 40 students/session, with an instructor to student ratio not exceeding 1:10. To practise hands-on compressions, the manikin to student ratio was 1:1. For a simulated cardiac arrest, the manikin and AED to student ratio was 1:10.

Primary And Secondary Outcomes: CPR and AED knowledge, attitude statements towards bystander CPR and AED, quality of BLS performance skills during training and at 3 months.

Results: Some students (46%) knew how deep to push on an adult chest when doing CO-CPR before training. The course was associated with an increase in knowledge score (pretraining 55%, post-training 93%; adjusted mean difference (MD) 38%, 95% CI 33% to 43%; p<0.001). Most students (68%) thought that CPR education in senior secondary school was essential before training. The students had a very positive attitude towards CPR; no change in the mean (SD) attitude score out of 30 over time (pretraining 27.2 (2.5), post-training 27.6 (2.7); adjusted MD 0.5, 95% CI -0.1 to 1.0; p=0.132). Most students were competent in performing BLS immediately after training (77%) and at 3 months (83%) (adjusted MD 6%, 95% CI -4% to 15%; p=0.268).

Conclusions: The results demonstrate the feasibility of scaling up the number of secondary schools trained in a brief CO-CPRAED course within the local school curriculum.
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http://dx.doi.org/10.1136/bmjopen-2020-040469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580074PMC
October 2020

Quality of life in individuals with Down syndrome aged 4 to 21 years.

Child Care Health Dev 2021 01 9;47(1):85-93. Epub 2020 Oct 9.

School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Background: To date, investigations of quality of life (QoL) in children with Down syndrome (DS) are rather limited. The purpose of this study was twofold: to examine QoL in children with DS and to explore possible differences in the QoL by age and gender.

Methods: A cross-sectional study of 211 parents of children with DS was conducted using an online survey that included a consent form, a demographic questionnaire and the English version of KidsLife, which is a measure of children's QoL.

Results: Our results demonstrated moderate or favourable levels of QoL except for the emotional well-being domain among children with DS. The children's QoL showed no variance by gender. However, emotional and material well-being, interpersonal relations and social inclusion varied by age.

Conclusions: The current findings provide important evidence that will help healthcare, educational and social services professionals to understand the multiple aspects of QoL in children with DS and support parents in their efforts to ensure the child's QoL. The results also point to the need to develop interventions aimed at improving QoL in those areas where children with DS are at increased risk for poorer QoL.
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http://dx.doi.org/10.1111/cch.12815DOI Listing
January 2021

First experience with the abdominal aortic and junctional tourniquet in prehospital traumatic cardiac arrest.

Resuscitation 2020 11 23;156:210-214. Epub 2020 Sep 23.

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Electronic address:

Introduction: The Abdominal Aortic and Junctional Tourniquet (AAJT) increased systemic vascular resistance, mean arterial pressure, carotid blood flow and rate of return of spontaneous circulation (ROSC) in animals with hypovolaemic traumatic cardiac arrest (TCA). The objective of this study was to report the first experience of the use of the AAJT as part of a pre-hospital TCA algorithm.

Methods: This is a descriptive case series of the use of the AAJT in patients with TCA in a civilian physician-led pre-hospital trauma service in Sydney, Australia between June 2015 to August 2019. Cases were identified and data sourced from routinely collected data sets within the retrieval service.

Results: During the study, 44 TCAs were attended, 22 with AAJT application. Mean time (standard deviation) to AAJT application since last signs of life was 16 (9) min. Eighteen (16 males, 2 females) patients, with median age (interquartile range) of 40 (25-58) years, were included for analysis. Seventeen patients (94%) had blunt trauma. Sixteen patients (89%) were in TCA at the time of service contact, 11 (61%) had a change in electrical activity, 4 (22%) had ROSC, and of the 6 with documented end-tidal carbon dioxide, the mean rise was 24.0 mmHg (95% CI 12.6-35.4) (P = 0.003). Three patients (17%) had sustained ROSC on arrival to the Emergency Department. No patients survived to hospital discharge.

Conclusion: Physiological changes were demonstrated but there were no survivors. Further research focusing on faster application times may be associated with improved outcomes.
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http://dx.doi.org/10.1016/j.resuscitation.2020.09.018DOI Listing
November 2020

The retention of fall-resisting behavior derived from treadmill slip-perturbation training in community-dwelling older adults.

Geroscience 2020 Sep 25. Epub 2020 Sep 25.

Department of Physical Therapy, University of Illinois at Chicago, 1919 W. Taylor Street, Fourth Floor, Chicago, IL, 60612, USA.

The purpose of this study was to determine whether and to what extent the immediate generalization of treadmill slip-perturbation training could be retained over 6 months to resist overground slip-induced falls. Four protocols (Tc: treadmill control; Tt: treadmill slip-perturbation training; Oc: overground control; Ot: overground slip-perturbation training) from two randomized controlled trials were compared in which two training protocols were executed with single-session repeated slip-perturbation training on the treadmill or overground context, while two control protocols were executed without repeated training. A total of 152 community-dwelling older adults (≥ 65 years) who were trained by one of the four protocols and tested by an overground slip in the initial session attended a retest session 6 months later. Falls were detected by a load cell. Data collected from motion analysis system and force plates were used to calculate stability. Tt group had no significant change in fall incidence from initial post-training test to retest. Tt group had significantly lower fall incidence (p < 0.05) and higher reactive stability (p < 0.05) than Tc group in retest. Tt group had significantly higher fall incidence (p < 0.05) and lower reactive stability (p < 0.01) than Ot group. The generalization of a single session of treadmill slip-perturbation training to overground slip resulted in inferior outcomes compared with overground slip-perturbation training (absolute retention), although the training generalization could be retained over 6 months (relative retention). Thus, treadmill slip-perturbation training could be more convenient to use if future dose-response studies indicate better or equal efficacy to overground slip-perturbation training.
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http://dx.doi.org/10.1007/s11357-020-00270-5DOI Listing
September 2020

Development and evaluation of stem cell collection procedure diagrams to support the education and recruitment of committed stem cell donors.

Vox Sang 2021 Feb 24;116(2):239-248. Epub 2020 Sep 24.

Canadian Blood Services, Ottawa, ON, Canada.

Background: Diagrams which allow potential unrelated stem cell donors to visualize the stem cell collection process were hypothesized to support the recruitment and education of committed stem cell donors.

Study Design And Methods: A series of bone marrow and peripheral blood stem cell collection procedure diagrams were developed, featuring young adult male donors of varied ethnic backgrounds. Post-implementation, surveys were conducted to evaluate stakeholder perspective on the diagrams' utility. A quality improvement project was conducted at five stem cell drives from 2017 to 2018 at which recruiters did or did not show the diagrams to potential donors. Following the drives, registrants were invited to complete a survey exploring their experience, knowledge and attitude towards donation.

Results: The diagrams were implemented in Canada in 07/2016. Of 293 participating registrants (24·7% non-Caucasian males) recruited at five drives between 2017 and 2018, 76% (n = 197) were shown the diagrams. Participants who were shown the diagrams were significantly more likely to report that the recruiters appeared very knowledgeable (89% vs. 76%, P = 0·019) and to report improved self-reported knowledge of stem cell donation (P = 0·010) compared to participants not shown the diagram. Data are also shown demonstrating that stakeholders in donor recruitment used and valued the diagrams and that use of the diagrams was associated with improved donor recruitment outcomes in Canada.

Conclusion: This report is the first evaluation of stem cell collection diagrams in the literature. The diagrams are relevant to donor registries, recruitment organizations and transplant centres worldwide, and their use may support efforts to educate and recruit committed, ethnically diverse donors.
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http://dx.doi.org/10.1111/vox.13010DOI Listing
February 2021

Challenges faced by women in radiology during the pandemic - A summary of the AAWR Women's Caucus at the ACR 2020 annual meeting.

Clin Imaging 2020 Dec 28;68:291-294. Epub 2020 Aug 28.

Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States; Vanderbilt Ingram Cancer Center, Nashville, TN, United States; Veterans' Health Administration - Tennessee Valley Healthcare System Geriatric Research, Education and Clinical Center, Nashville, TN, United States. Electronic address:

The COVID-19 pandemic has dramatically altered the professional and personal lives of radiologists and radiation oncologists. This article summarizes the 2020 American Association for Women in Radiology (AAWR) Women's Caucus at the American College of Radiology (ACR) Annual Meeting. The caucus focused on the major challenges that women in radiology have faced during the pandemic.
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http://dx.doi.org/10.1016/j.clinimag.2020.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453221PMC
December 2020