Publications by authors named "Jenny Chen"

171 Publications

Temporal changes and risk factors of death from early withdrawal within 12 months of dialysis initiation - a cohort study.

Nephrol Dial Transplant 2021 Jun 27. Epub 2021 Jun 27.

Medical School, University of Western Australia, Perth, Australia.

Background: Mortality risk is high soon after dialysis initiation in patients with kidney failure, and dialysis withdrawal is a major cause of early mortality, attributed to psychosocial or medical reasons. The temporal trends and risk factors associated with cause-specific early dialysis withdrawal within 12 months of dialysis initiation remain uncertain.

Methods: Using data from the Australian and New Zealand Dialysis and Transplant Registry, we examined the temporal trends and risk factors associated with mortality attributed to early psychosocial and medical withdrawals in incident adult dialysis patients in Australia between 2005 and 2018 using adjusted competing risk analyses.

Results: Of 32,274 incident dialysis patients, 3390 (11%) experienced death within 12 months post-dialysis initiation. Of these, 1225 (36%) were attributed to dialysis withdrawal, with 484 (14%) psychosocial withdrawals and 741 (22%) medical withdrawals. These patterns remained unchanged over the past two decades. Factors associated with increased risk of death from early psychosocial and medical withdrawals were older age, dialysis via central venous catheter, late referral, and the presence of cerebrovascular disease; while obesity and Asian ethnicity were associated with decreased risk. Risk factors associated with early psychosocial withdrawals were underweight and higher socioeconomic status. Presence of peripheral vascular disease, chronic lung disease, and cancers were associated with early medical withdrawals.

Conclusions: Death from dialysis withdrawal accounted for over 30% of early deaths in kidney failure patients initiated on dialysis and remained unchanged over the past two decades. Several shared risk factors were observed between mortality attributed to early psychosocial and medical withdrawals.
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http://dx.doi.org/10.1093/ndt/gfab207DOI Listing
June 2021

First Asian population study of stereotactic body radiation therapy for ventricular arrhythmias.

Sci Rep 2021 May 14;11(1):10360. Epub 2021 May 14.

Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, No. 7, Chuang-Shan South Road, Taipei, 100, Taiwan.

We report the first Asian series on stereotactic body radiation (SBRT) for refractory ventricular arrhythmia (VA) in Taiwanese patients. Three-dimensional electroanatomic maps, delayed-enhancement magnetic resonance imaging (DE-MRI), and dual-energy computed tomography (CT) were used to identify scar substrates. The main target volume was treated with a single radiation dose of 25 Gy and the margin volume received 20 Gy using simultaneous integrated boost delivered by the Varian TrueBeam system. Efficacy was assessed according to VA events recorded by an implantable cardioverter-defibrillator (ICD) or a 24-h Holter recorder. Pre- and post-radiation therapy imaging studies were performed. From February 2019 to December 2019, seven patients (six men, one woman; mean age, 55 years) were enrolled and treated. One patient died of hepatic failure. In the remaining six patients, at a median follow-up of 14.5 months, the VA burden and ICD shocks significantly decreased (only one patient with one ICD shock after treatment). Increased intensity on DE-MRI might be associated with a lower risk for VA recurrence, whereas dual-energy CT had lower detection sensitivity. No acute or minimal late adverse events occurred. In patients with refractory VA, SBRT is associated with a marked reduction in VA burden and ICD shocks, and DE-MRI might be useful for monitoring treatment effects.
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http://dx.doi.org/10.1038/s41598-021-89857-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121933PMC
May 2021

Opioid prescribing practices in academic otolaryngology: A single institutional survey.

Am J Otolaryngol 2021 Apr 15;42(5):103038. Epub 2021 Apr 15.

Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA; Department of Otolaryngology, Harvard Medical School, Boston, MA, USA.

Objectives: Opioids are highly addictive medications and otolaryngologists have a responsibility to practice opioid stewardship. We investigated postoperative opioid prescribing patterns among resident and attending physicians as an educational platform to underscore the importance of conscientious opioid prescribing.

Methods: This quality improvement study was designed as a cross-sectional electronic survey. Residents and attending clinical faculty members at a single academic institution were queried from February through April 2020. An electronic survey was distributed to capture postoperative opioid prescribing patterns after common procedures. At the conclusion of the study, results were sent to all faculty and residents.

Results: A total of 29 attending otolaryngologists and 22 residents completed the survey. Resident physicians prescribed on average fewer postoperative opioid pills than attendings. Among attendings, the largest number of opioids were prescribed following tonsillectomy (dose varied by patient age), neck dissection (12.6 pills), brow lift (13.3 pills), facelift (13.3 pills), and open reduction of facial trauma (10.7 pills). For residents, surgeries with the most postoperatively prescribed opioids were for tonsillectomy (varied by patient age), neck dissection (13.4 pills), open reduction of facial trauma (10.5 pills), parotidectomy (10.0 pills), and thyroid/parathyroidectomy (9.0 pills). The largest volume of postoperative opioids for both groups was prescribed following tonsillectomy. Attendings prescribed significantly more opioids after facelift and brow lift than did residents (p = 0.01 and p = 0.003, respectively).

Conclusion: There was good concordance between resident and attending prescribers. Improvement in opioid prescribing and pain management should be an essential component of otolaryngology residency education and attending continuing medical education.

Level Of Evidence: 4.
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http://dx.doi.org/10.1016/j.amjoto.2021.103038DOI Listing
April 2021

Graduate Medical Education in Otolaryngology: Making Dollars and Sense of Reform.

Otolaryngol Head Neck Surg 2021 Apr 13:1945998211004263. Epub 2021 Apr 13.

Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts, USA.

Graduate medical education (GME) is funded by the Centers for Medicare and Medicaid Services through both direct and indirect payments. In recent years, stakeholders have raised concerns about the growth of spending on GME and distribution of payment among hospitals. Key stakeholders have proposed reforms to reduce GME funding such as adjustments to statutory payment formulas and absolute caps on annual payments per resident. Otolaryngology departmental leadership should understand the potential effects of proposed reforms, which could have significant implications for the short-term financial performance and the long-term specialty workforce. Although some hospitals and departments may elect to reduce resident salaries or eliminate positions in the face of GME funding cuts, this approach overlooks the substantial Medicare revenue contributed by resident care and high cost of alternative labor sources. Commitment to resident training is necessary to align both the margin and mission of otolaryngology departments and their sponsoring hospitals.
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http://dx.doi.org/10.1177/01945998211004263DOI Listing
April 2021

Real-World Evaluation of Modern Adjuvant Radiotherapy in Women with Stage IB Endometrial Cancer.

Cancers (Basel) 2021 Mar 18;13(6). Epub 2021 Mar 18.

Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei 100, Taiwan.

The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI); low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS); patients with age >60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients.
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http://dx.doi.org/10.3390/cancers13061386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003240PMC
March 2021

Assessing tumor angiogenesis using dynamic contrast-enhanced integrated magnetic resonance-positron emission tomography in patients with non-small-cell lung cancer.

BMC Cancer 2021 Apr 1;21(1):348. Epub 2021 Apr 1.

Department of Radiology, National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei, 100, Taiwan.

Background: Angiogenesis assessment is important for personalized therapeutic intervention in patients with non-small-cell lung cancer (NSCLC). This study investigated whether radiologic parameters obtained by dynamic contrast-enhanced (DCE)-integrated magnetic resonance-positron emission tomography (MR-PET) could be used to quantitatively assess tumor angiogenesis in NSCLC.

Methods: This prospective cohort study included 75 patients with NSCLC who underwent DCE-integrated MR-PET at diagnosis. The following parameters were analyzed: metabolic tumor volume (MTV), maximum standardized uptake value (SUV), reverse reflux rate constant (k), volume transfer constant (K), blood plasma volume fraction (v), extracellular extravascular volume fraction (v), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC). Serum biomarkers of tumor angiogenesis, including vascular endothelial growth factor-A (VEGF-A), angiogenin, and angiopoietin-1, were measured by enzyme-linked immunosorbent assays simultaneously.

Results: Serum VEGF-A (p = 0.002), angiogenin (p = 0.023), and Ang-1 (p <  0.001) concentrations were significantly elevated in NSCLC patients compared with healthy individuals. MR-PET parameters, including MTV, K, and k, showed strong linear correlations (p <  0.001) with serum angiogenesis-related biomarkers. Serum VEGF-A concentrations (p = 0.004), MTV values (p <  0.001), and k values (p = 0.029) were significantly higher in patients with advanced-stage disease (stage III or IV) than in those with early-stage disease (stage I or II). Patients with initial higher values of angiogenesis-related MR-PET parameters, including MTV > 30 cm (p = 0.046), K > 200 10/min (p = 0.069), and k > 900 10/min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival.

Conclusions: The present findings suggest that DCE-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC.
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http://dx.doi.org/10.1186/s12885-021-08064-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017855PMC
April 2021

'Now my life is stuck!': Experiences of adolescents and young people during COVID-19 lockdown in South Africa.

Glob Public Health 2021 06 22;16(6):947-963. Epub 2021 Mar 22.

Centre for Social Science Research, University of Cape Town, Cape Town, South Africa.

Consequences of COVID-19 pandemic responses have included exacerbated poverty, food insecurity and state and domestic violence. Such effects may be particularly pronounced amongst adolescents and young people living in contexts of precarity and constraint, including in South Africa. However, there are evidence gaps on the lived experiences of this group. We conducted telephonic semi-structured interviews with adolescents and young people in two South African provinces ( = 12, ages 18-25) in April 2020 to explore and document their experiences, challenges and coping strategies during strict COVID-19 lockdown. Participants described indirect effects of COVID-19 including food insecurity, lost livelihoods and changes to social service provisions such as municipal electricity services and sanitation. Psychosocial stressors related to uncertainty over education and work futures were also discussed. The aforementioned challenges were particularly present with young parents, 'working poor' participants, and those with pre-existing mental health challenges. Participants demonstrated excellent COVID-19 transmission and prevention knowledge, showing that they had received and correctly interpreted public health messaging. Despite this, many simultaneously held non-scientific COVID-19 beliefs. Engaging a socio ecological framework, findings demonstrate how the indirect effects of COVID-19 may exacerbate underlying multi-layered vulnerabilities for adolescents and young people living in contexts of precarity and constraint.
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http://dx.doi.org/10.1080/17441692.2021.1899262DOI Listing
June 2021

Dispositional optimism mediates relations between childhood maltreatment and PTSD symptom severity among trauma-exposed adults.

Child Abuse Negl 2021 May 13;115:105023. Epub 2021 Mar 13.

Department of Psychiatry, University of Toledo, Toledo, OH 43606, USA. Electronic address:

Background: Experiences of maltreatment in childhood, such as abuse and neglect, have been associated with poorer psychological well-being in adulthood, including elevated risk of revictimization and increased likelihood of developing posttraumatic stress disorder (PTSD) symptoms. Maltreatment has also been associated with reduced resources related to resilience, such as optimism, which may act as a protective factor for mental health.

Objectives: In this study, we examined the mediating role of dispositional optimism in the relationship between childhood maltreatment and PTSD symptom severity from recent trauma in a sample of adults (n = 108) who presented to their local emergency department following trauma.

Methods: We analyzed six models to account for cumulative childhood maltreatment as well as five primary subtypes of maltreatment: emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect.

Results: Greater dispositional optimism mediated relations between total maltreatment and decreased PTSD severity (B = .056, SE = .029, 95 % CI [.009, .121]). Optimism also mediated relations between all maltreatment subtypes and PTSD severity, except sexual abuse.

Conclusions: These results may suggest optimism and positive psychology interventions as effective techniques in reducing the likelihood of PTSD development and severity in trauma-exposed individuals.
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http://dx.doi.org/10.1016/j.chiabu.2021.105023DOI Listing
May 2021

A retrospective study of clinicopathologic and molecular features of inoperable early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

J Formos Med Assoc 2021 Jan 12. Epub 2021 Jan 12.

Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address:

Background/purpose: Stereotactic ablative radiotherapy (SABR) is the treatment of choice for medically inoperable, early-stage non-small cell lung cancer (ES-NSCLC). The influence of oncogenic driver alterations and comorbidities are not well known. Here we present treatment outcomes based on clinicopathologic features and molecular profiles.

Methods: We retrospectively analyzed patients treated with SABR for inoperable ES-NSCLC. Molecular features of oncogenic driver alterations included EGFR, ALK, and ROS1. Comorbidities were assessed using the age-adjusted Charlson Comorbidity Index (ACCI). Survival was calculated using the Kaplan-Meier method. The Cox regression model was performed for univariate and multivariate analyses of prognostic factors. Competing risk analysis was used to evaluate the cumulative incidence of disease progression.

Results: From 2008 to 2020, 100 patients (median age: 82 years) were enrolled. The majority of patients were male (64%), ever-smokers (60%), and had adenocarcinoma (65%). With a median follow-up of 21.5 months, the median overall survival (OS) and real-world progression-free survival were 37.7 and 25.1 months, respectively. The competing-risk-adjusted 3-year cumulative incidences of local, regional, and disseminated failure were 8.2%, 14.5%, and 31.2%, respectively. An ACCI ≥7 was independently associated with inferior OS (hazard ratio [HR] 2.45, p = 0.03). Tumor size ≥4 cm (HR 4.16, p < 0.001) was the most important independent prognostic factor predicting real-world progression. EGFR mutation status had no impact on the outcomes.

Conclusion: SABR provides excellent local control in ES-NSCLC, although disseminated failures remains a major concern. ACCI is the best indicator for OS, while tumor sizes ≥4 cm predicts poor disease control.
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http://dx.doi.org/10.1016/j.jfma.2020.12.028DOI Listing
January 2021

Assessment of metastatic lymph nodes in head and neck squamous cell carcinomas using simultaneous F-FDG-PET and MRI.

Sci Rep 2020 11 27;10(1):20764. Epub 2020 Nov 27.

Department of Radiology, Center for Biomedical Imaging (CBI), Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, 660 First Avenue, New York, NY, 10016, USA.

In this study, we investigate the feasibility of using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), diffusion weighted imaging (DWI), and dynamic positron emission tomography (PET) for detection of metastatic lymph nodes in head and neck squamous cell carcinoma (HNSCC) cases. Twenty HNSCC patients scheduled for lymph node dissection underwent DCE-MRI, dynamic PET, and DWI using a PET-MR scanner within one week prior to their planned surgery. During surgery, resected nodes were labeled to identify their nodal levels and sent for routine clinical pathology evaluation. Quantitative parameters of metastatic and normal nodes were calculated from DCE-MRI (v, v, PS, F, K), DWI (ADC) and PET (K, K, k, k) to assess if an individual or a combination of parameters can classify normal and metastatic lymph nodes accurately. There were 38 normal and 11 metastatic nodes covered by all three imaging methods and confirmed by pathology. 34% of all normal nodes had volumes greater than or equal to the smallest metastatic node while 4 normal nodes had SUV > 4.5. Among the MRI parameters, the median v, F, PS, and K values of the metastatic lymph nodes were significantly lower (p = <0.05) than those of normal nodes. v and ADC did not show any statistical significance. For the dynamic PET parameters, the metastatic nodes had significantly higher k (p value = 8.8 × 10) and K (p value = 5.3 × 10) than normal nodes. K and k did not show any statistically significant difference. K had the best separation with accuracy = 0.96 (sensitivity = 1, specificity = 0.95) using a cutoff of K = 5.3 × 10 mL/cm/min, while k and volume had accuracy of 0.94 (sensitivity = 0.82, specificity = 0.97) and 0.90 (sensitivity = 0.64, specificity = 0.97) respectively. 100% accuracy can be achieved using a multivariate logistic regression model of MRI parameters after thresholding the data with K < 5.3 × 10 mL/cm/min. The results of this preliminary study suggest that quantitative MRI may provide additional value in distinguishing metastatic nodes, particularly among small nodes, when used together with FDG-PET.
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http://dx.doi.org/10.1038/s41598-020-77740-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695736PMC
November 2020

A retrospective study on the epidemiology of ANCA-associated vasculitis in two Australian health districts.

Intern Med J 2020 Oct 11. Epub 2020 Oct 11.

Department of Renal Medicine, The Wollongong Hospital, Wollongong, NSW, Australia.

Background: ANCA-associated vasculitis (AAV) is more prevalent in rural Australia compared to metropolitan areas suggesting a role of environment in disease pathogenesis. However, the prevalence of environmental risk factors in Australian AAV patients has not been described.

Aims: To compare the incidence of AAV between two health districts (Illawarra Shoalhaven local health district (ISLHD), a mixed rural/metropolitan region, and South Eastern Sydney local health district (SESLHD), a metropolitan region) in Australia and its relationship to environmental exposures.

Methods: Cases of AAV from 2002 to 2017 were retrospectively identified from ISLHD and SESLHD using electronic medical records. Eligible participants were invited to complete a standardised questionnaire examining their exposure to silica, solvents, metal, dust, farming, gardening, and sunlight.

Results: 156 cases of AAV were identified from 2002 to 2017. A higher cumulative incidence of AAV was observed in the ISLHD (184.2 [95% confidence interval (CI) 143.6-232.7] per million) compared to SESLHD (102.6 [95% CI 82.1-126.8] per million). Over 50% of the cohort had high levels of silica and solvents exposure, based on self-reported questionnaires. There was no significant relationship between region and exposure to silica (p=0.96), solvents (p=0.44), metal (p=0.33), dust (p=0.25), farming (p=0.90), gardening (p=0.93), or sunlight (p=0.55).

Conclusions: We found a higher incidence of AAV in ISLHD compared to SESLHD with high levels of exposure to silica and solvents in both regions based on self-reported questionnaires. Prospective systematic collection of data, such as a registry of AAV, is warranted to further explore the relationship between environmental exposures and AAV. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15098DOI Listing
October 2020

Fluctuations in Subjective Tinnitus Ratings Over Time: Implications for Clinical Research.

Otol Neurotol 2020 10;41(9):e1167-e1173

Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School.

Objective: Patients with chronic, subjective tinnitus are often administered a battery of audiometric tests to characterize their tinnitus percept. Even a comprehensive battery, if applied just once, cannot capture fluctuations in tinnitus strength or quality over time. Moreover, subjects experience a learning curve when reporting the detailed characteristics of their tinnitus percept, such that a single assessment will reflect a lack of familiarity with test requirements. We addressed these challenges by programming an automated software platform for at-home tinnitus characterization over a 2-week period.

Study Design: Prospective case series.

Setting: Tertiary referral center, patients' homes.

Interventions: Following an initial clinic visit, 25 subjects with chronic subjective tinnitus returned home with a tablet computer and calibrated headphones to complete questionnaires, hearing tests, and tinnitus psychoacoustic testing. We repeatedly characterized loudness discomfort levels and tinnitus matching over a 2-week period.

Main Outcome Measures: Primary outcomes included intrasubject variability in loudness discomfort levels, tinnitus intensity, and tinnitus acoustic matching over the course of testing.

Results: Within-subject variability for all outcome measures could be reduced by approximately 25 to 50% by excluding initial measurements and by focusing only on tinnitus matching attempts where subjects report high confidence in the accuracy of their ratings.

Conclusions: Tinnitus self-report is inherently variable but can converge on reliable values with extended testing. Repeated, self-directed tinnitus assessments may have implications for identifying malingerers. Further, these findings suggest that extending the baseline phase of tinnitus characterizations will increase the statistical power for future studies focused on tinnitus interventions.
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http://dx.doi.org/10.1097/MAO.0000000000002759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114831PMC
October 2020

Demonstration and Mitigation of Aerosol and Particle Dispersion During Mastoidectomy Relevant to the COVID-19 Era.

Otol Neurotol 2020 10;41(9):1230-1239

Department of Otolaryngology - Head and Neck Surgery, Massachusetts Eye and Ear.

Background: COVID-19 has become a global pandemic with a dramatic impact on healthcare systems. Concern for viral transmission necessitates the investigation of otologic procedures that use high-speed drilling instruments, including mastoidectomy, which we hypothesized to be an aerosol-generating procedure.

Methods: Mastoidectomy with a high-speed drill was simulated using fresh-frozen cadaveric heads with fluorescein solution injected into the mastoid air cells. Specimens were drilled for 1-minute durations in test conditions with and without a microscope. A barrier drape was fashioned from a commercially available drape (the OtoTent). Dispersed particulate matter was quantified in segments of an octagonal test grid measuring 60 cm in radius.

Results: Drilling without a microscope dispersed fluorescent particles 360 degrees, with the areas of highest density in quadrants near the surgeon and close to the surgical site. Using a microscope or varying irrigation rates did not significantly reduce particle density or percent surface area with particulate. Using the OtoTent significantly reduced particle density and percent surface area with particulate across the segments of the test grid beyond 30 cm (which marked the boundary of the OtoTent) compared with the microscope only and no microscope test conditions (Kruskall-Wallis test, p = 0.0066).

Conclusions: Mastoidectomy with a high-speed drill is an aerosol-generating procedure, a designation that connotes the potential high risk of viral transmission and need for higher levels of personal protective equipment. A simple barrier drape significantly reduced particulate dispersion in this study and could be an effective mitigation strategy in addition to appropriate personal protective equipment.
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http://dx.doi.org/10.1097/MAO.0000000000002765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497894PMC
October 2020

Using Guided Imagery to Relieve the Anxiety of Preschool Children Undergoing Dental Procedures.

J Perianesth Nurs 2021 Feb 8;36(1):18-23. Epub 2020 Sep 8.

Department of Anesthesia, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan; Department of Medicine, Chang Gung University, Linkou, Taipei, Taiwan. Electronic address:

Purpose: Negative experiences in dental clinics can induce anxiety in patients, and the effects are particularly pronounced in children. When behavior guidance methods (eg, direct observation, tell-show-do, and ask-tell-ask) fail, general anesthesia is an important alternative; however, the procedure of anesthesia can also induce fear and anxiety. This study assessed the effectiveness of guided imagery in relieving the anxiety associated with dental surgery in children and caregivers.

Design: A prospective randomized trial with two groups.

Methods: The guided imagery in this study was meant to establish a rapport between the medical team and the patient, by encouraging the child to imagine having an adventure while riding in a spacecraft. Anxiety levels and behavior were measured using five well-established scales: the modified Yale Preoperative Scale-Short Form, the State-Trait Anxiety Inventory-6 items, the Watcha score, the Pediatric Anesthesia Emergent Delirium scale, and the Posthospitalization Behavioral Questionnaire-Ambulatory Surgery.

Findings: The results indicate that the guided imagery had no significant effects on anxiety levels.

Conclusions: Guided imagery is a low-cost, easy-to-implement, interesting exercise capable of enhancing interactions between nursing staff and children. It may also help to condition children to the environment and thereby assist them in overcoming their fears.
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http://dx.doi.org/10.1016/j.jopan.2020.04.007DOI Listing
February 2021

Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial.

Neuro Oncol 2021 03;23(3):478-486

Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

Background: Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT (C-WBRT) is better for preserving neurocognitive function.

Methods: This single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned them to receive HA-WBRT or C-WBRT. Primary endpoint is decline of the Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

Results: From March 2015 to December 2018, seventy patients were randomized to yield a total cohort of 65 evaluable patients (33 in the HA-WBRT arm and 32 in the C-WBRT arm) with a median follow-up of 12.4 months. No differences in baseline neurocognitive function existed between the 2 arms. The mean change of HVLT-R delayed recall at 4 months was -8.8% in the HA-WBRT arm and +3.8% in the C-WBRT arm (P = 0.31). At 6 months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, P = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, P = 0.019) and memory score (mean difference = 4.38, P = 0.020) compared with patients undergoing C-WBRT. There were no differences in Trail Making Test Part A or Part B or the Controlled Oral Word Association test between the 2 arms at any time point. There were no differences in brain PFS or OS between arms as well.

Conclusion: Patients receiving HA-WBRT without memantine showed better preservation in memory at 6-month follow-up, but not in verbal fluency or executive function.
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http://dx.doi.org/10.1093/neuonc/noaa193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992885PMC
March 2021

Evaluation of antitumor immunity by a combination treatment of high-dose irradiation, anti-PDL1, and anti-angiogenic therapy in murine lung tumors.

Cancer Immunol Immunother 2021 Feb 6;70(2):391-404. Epub 2020 Aug 6.

Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.

C57BL/6 mice implanted in the flank with murine Lewis lung carcinoma cells were randomized into control, anti-angiogenic, anti-PD-L1, radiotherapy (RT), RT + anti-angiogenic, RT + anti-PD-L1, and RT + anti-PD-L1 + anti-angiogenic therapy groups. Immune response and immunophenotyping were determined by flow cytometry. Vasculature analysis after RT and anti-angiogenic therapy was assessed by quantified power Doppler sonography. Antitumor response, survival, and rechallenged tumor growth were evaluated. RT increased PD-L1 expression on CD8+ T, CD4+ T, dendritic, myeloid-derived suppressor cells (MDSCs), and tumor cells and increased PD-1 expression on CD8+ and CD4+ T cells. Anti-angiogenic therapy insignificantly decreased the RT-induced PD-1 expression on CD8+ and CD4+ T cells, implying a weak reversal of the immune-suppressive environment. Transient vessel collapse was observed within days after RT, and blood flow recovered at 1 week after RT. RT + anti-PD-L1 suppressed the tumor growth, improved survival, and prolonged immune memory capable of protecting against tumor recurrence, evidenced by local accumulation of CD8+ T cells and reduction in MDSCs in microenvironment. Similar and more prominent effects were observed when anti-VEGF was added to RT + anti-PDL1 therapies, implying an additive, rather than synergistic, antitumor immunity. Phenotypic analyses revealed that anti-cancer treatments increased the proportion of effector memory T cells in TILs and splenocytes, and RT, alone or in combination with other treatments, further increased the proportion of central memory T cells in splenocytes. These results provide evidence on operating the immunosuppressive tumor environment and offer insights into the design of the new combination treatment.
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http://dx.doi.org/10.1007/s00262-020-02690-wDOI Listing
February 2021

Impacts of Post-Hospitalization Accessible Health Technology and Caregiver Support on 90-Day Acute Care Use and Self-Care Assistance: A Randomized Clinical Trial.

Am J Med Qual 2021 May-Jun 01;36(3):145-155

Ann Arbor Department of Veterans Affairs Center for Clinical Management Research, Ann Arbor, MI University of Michigan, Ann Arbor, MI University of Mississippi, Oxford, MS MidMichigan Health Network, Midland, MI University of Washington, Seattle, WA.

Hospitalized patients often are readmitted soon after discharge, with many hospitalizations being potentially preventable. The authors evaluated a mobile health intervention designed to improve post-hospitalization support for older adults with common chronic conditions. All participants enrolled with an informal caregiver or "CarePartner" (CP). Intervention patients received automated assessment and behavior change calls. CPs received automated, structured feedback following each assessment. Clinicians received alerts about serious problems identified during patient calls. Controls had a 65% greater risk of hospitalization within 90 days post discharge than intervention patients (P = .041). For every 6.8 enrollees, the intervention prevented 1 rehospitalization or emergency department encounter. The intervention improved physical functioning at 90 days (P = .012). The intervention also improved medication adherence and indicators of the quality of communication with CPs (all P < .01). Automated telephone patient monitoring and self-care advice with feedback to primary care teams and CPs reduces readmission rates over 90 days.
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http://dx.doi.org/10.1177/1062860620943673DOI Listing
July 2020

Elevated Interleukin-6 Levels Predict Clinical Worsening in Pediatric Pulmonary Arterial Hypertension.

J Pediatr 2020 08;223:164-169.e1

Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD. Electronic address:

Objective: To assess whether circulating interleukin-6 (IL-6) is associated with measures of disease severity and clinical worsening in pediatric pulmonary arterial hypertension (PAH).

Study Design: IL-6 was measured by enzyme-linked immunosorbent assay in serum samples from a cross-sectional cohort from the National Heart, Lung, and Blood Institute Pulmonary Arterial Hypertension Biobank (n = 175) and a longitudinal cohort from Children's Hospital Colorado (CHC) (n = 61). Associations between IL-6, disease severity, and outcomes were studied with regression and Kaplan-Meier analysis.

Results: In analyses adjusted for age and sex, each log-unit greater IL-6 was significantly associated in the Pulmonary Arterial Hypertension Biobank cohort with greater pulmonary vascular resistance indices, lower odds of having idiopathic PAH or treatment with prostacyclin, and greater odds of having PAH associated with a repaired congenital shunt. In the CHC cohort, each log-unit greater IL-6 was significantly associated with greater mean pulmonary arterial pressure over time. Kaplan-Meier analysis in the CHC cohort revealed that IL-6 was significantly associated with clinical worsening (a composite score of mortality, transplant, or palliative surgery) (P = .037).

Conclusions: IL-6 was significantly associated with worse hemodynamics at baseline and over time and may be associated with clinical worsening. IL-6 may provide a less-invasive method for disease monitoring and prognosis in pediatric PAH as well as a potential therapeutic target.
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http://dx.doi.org/10.1016/j.jpeds.2020.04.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388069PMC
August 2020

Risk Factors for Complications and Failure after Gonioscopy-Assisted Transluminal Trabeculotomy in a Young Cohort.

Ophthalmol Glaucoma 2020 May - Jun;3(3):190-195. Epub 2020 Feb 20.

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.

Purpose: To determine the risk factors for failures and complications of gonioscopy-assisted transluminal trabeculotomy (GATT) in a young cohort.

Design: Retrospective case series.

Participants: Eyes that underwent GATT at Bascom Palmer Eye Institute.

Methods: Preoperative and postoperative intraocular pressure (IOP), extent of angle treated, postoperative IOP spike, postoperative drop regimen, and postoperative failure were recorded. Failure was defined as (1) IOP of more than 21 mmHg or less than 5 mmHg after postoperative month 3, (2) absence of at least 20% reduction from the preoperative IOP baseline after postoperative month 3, or (3) performance of additional IOP-lowering surgery before postoperative month 3. Intraocular pressure spike complication was defined as an increase in IOP in the operated eye at any postoperative visit to higher than preoperative IOP within the first 3 months. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the time to events (failure and IOP spike).

Main Outcome Measures: Risk of failure associated with any of the preoperative, intraoperative, or postoperative variables.

Results: A total of 102 eyes of 88 patients were included. The median follow-up time was 7.4 months, with an interquartile range of 3.3 to 13.1 months (standard deviation, 8.7 months). Patients who used corticosteroids after surgery were more likely to experience IOP spikes than those using nonsteroidal anti-inflammatory drugs (NSAIDs) alone (hazard ratio, 3.34; P = 0.042), and patients who underwent noncircumferential trabeculotomy were 2.56 times more likely to experience treatment failure (P = 0.002) compared with those who underwent circumferential surgery.

Conclusions: Eyes that received postoperative corticosteroids were more likely to experience an IOP spike complication than those that received postoperative NSAIDs alone, which may suggest corticosteroid-mediated outflow obstruction distal to the trabecular meshwork. Achieving a circumferential trabeculotomy and using only NSAIDs may be more likely to result in surgical success when compared with noncircumferential trabeculotomy or using postoperative corticosteroids.
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http://dx.doi.org/10.1016/j.ogla.2020.02.002DOI Listing
February 2020

Aerosol Dispersion During Mastoidectomy and Custom Mitigation Strategies for Otologic Surgery in the COVID-19 Era.

Otolaryngol Head Neck Surg 2021 01 14;164(1):67-73. Epub 2020 Jul 14.

Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.

Objective: To investigate small-particle aerosolization from mastoidectomy relevant to potential viral transmission and to test source-control mitigation strategies.

Study Design: Cadaveric simulation.

Setting: Surgical simulation laboratory.

Methods: An optical particle size spectrometer was used to quantify 1- to 10-µm aerosols 30 cm from mastoid cortex drilling. Two barrier drapes were evaluated: OtoTent1, a drape sheet affixed to the microscope; OtoTent2, a custom-structured drape that enclosed the surgical field with specialized ports.

Results: Mastoid drilling without a barrier drape, with or without an aerosol-scavenging second suction, generated large amounts of 1- to 10-µm particulate. Drilling under OtoTent1 generated a high density of particles when compared with baseline environmental levels ( < .001, = 107). By contrast, when drilling was conducted under OtoTent2, mean particle density remained at baseline. Adding a second suction inside OtoTent1 or OtoTent2 kept particle density at baseline levels. Significant aerosols were released upon removal of OtoTent1 or OtoTent2 despite a 60-second pause before drape removal after drilling ( < .001, = 0, n = 10, 12; < .001, = 2, n = 12, 12, respectively). However, particle density did not increase above baseline when a second suction and a pause before removal were both employed.

Conclusions: Mastoidectomy without a barrier, even when a second suction was added, generated substantial 1- to 10-µm aerosols. During drilling, large amounts of aerosols above baseline levels were detected with OtoTent1 but not OtoTent2. For both drapes, a second suction was an effective mitigation strategy during drilling. Last, the combination of a second suction and a pause before removal prevented aerosol escape during the removal of either drape.
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http://dx.doi.org/10.1177/0194599820941835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361126PMC
January 2021

Incidence and factors associated with geographical relocation in patients receiving renal replacement therapy.

BMC Nephrol 2020 07 1;21(1):249. Epub 2020 Jul 1.

Renal Unit, Wollongong Hospital, Locked Bag 8808, South Coast Mail Centre, Wollongong, NSW, 2521, Australia.

Background: Renal replacement therapy (RRT) places a burden on patients, and geographical relocation for easier access to healthcare facilities is a necessity for some. Incidence and factors associated with relocation has not been comprehensively examined at a national level. We aimed to determine proportion, incidence, characteristics of RRT patients who relocate and relocation rate by remoteness of residence and dialysis modality.

Methods: Retrospective cohort analysis using Australian and New Zealand Dialysis and Transplant Registry to examine RRT patients in Australia from January 2005 to December 2015. Relocation incidence was calculated for remoteness of residence and RRT modality as rate per 100 patient years. Factors associated with relocation were examined using competing risk regression models with death as a competing event.

Results: Of 24,676 incident patients on RRT, 5888 (23.9%) relocated with a median time of 1.6 years [IQR 0.7-3.4] years. Relocation incidence was 7.9 per 100 patient years and increased from major cities to very remote regions (7.2 to 48.8 per 100 patient years respectively, p < 0.001). Remoteness of residence was associated with geographical relocation in competing risk analysis especially in remote (SHR 1.20, 95%CI 1.01, 1.41 p = 0.034) and very remote regions (SHR 3.51 95% 3.05, 4.04 p < 0.001). Aboriginal or Torres Strait Islander ethnicity, compared to Caucasian, was independently associated with relocation (SHR 1.18, 95% CI 1.06,1.31, p = 0.002) while transplant patients were less likely to relocate compared to haemodialysis patients (HR 0.37, 95%CI 0.34, 0.39, p < 0.001).

Conclusions: Relocation in patients receiving RRT is associated with remoteness of residence, RRT modality and ethnicity. Reasons for relocation and its impact on patient wellbeing and outcome should be further explored.
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http://dx.doi.org/10.1186/s12882-020-01887-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329545PMC
July 2020

Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020.

JAMA Intern Med 2020 10;180(10):1336-1344

Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland.

Importance: Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19.

Objective: To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020.

Design, Setting, And Population: This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020.

Main Outcomes And Measures: Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data.

Results: There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths.

Conclusions And Relevance: Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.
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http://dx.doi.org/10.1001/jamainternmed.2020.3391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330834PMC
October 2020

Reconstructing and forecasting the COVID-19 epidemic in the United States using a 5-parameter logistic growth model.

Glob Health Res Policy 2020 15;5:25. Epub 2020 May 15.

4Department of Statistics and Data Science, Cornell University, Ithaca, USA.

Background: Many studies have modeled and predicted the spread of COVID-19 (coronavirus disease 2019) in the U.S. using data that begins with the first reported cases. However, the shortage of testing services to detect infected persons makes this approach subject to error due to its underdetection of early cases in the U.S. Our new approach overcomes this limitation and provides data supporting the public policy decisions intended to combat the spread of COVID-19 epidemic.

Methods: We used Centers for Disease Control and Prevention data documenting the daily new and cumulative cases of confirmed COVID-19 in the U.S. from January 22 to April 6, 2020, and reconstructed the epidemic using a 5-parameter logistic growth model. We fitted our model to data from a 2-week window (i.e., from March 21 to April 4, approximately one incubation period) during which large-scale testing was being conducted. With parameters obtained from this modeling, we reconstructed and predicted the growth of the epidemic and evaluated the extent and potential effects of underdetection.

Results: The data fit the model satisfactorily. The estimated daily growth rate was 16.8% overall with 95% CI: [15.95, 17.76%], suggesting a doubling period of 4 days. Based on the modeling result, the tipping point at which new cases will begin to decline will be on April 7th, 2020, with a peak of 32,860 new cases on that day. By the end of the epidemic, at least 792,548 (95% CI: [789,162, 795,934]) will be infected in the U.S. Based on our model, a total of 12,029 cases were not detected between January 22 (when the first case was detected in the U.S.) and April 4.

Conclusions: Our findings demonstrate the utility of a 5-parameter logistic growth model with reliable data that comes from a specified period during which governmental interventions were appropriately implemented. Beyond informing public health decision-making, our model adds a tool for more faithfully capturing the spread of the COVID-19 epidemic.
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http://dx.doi.org/10.1186/s41256-020-00152-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225094PMC
January 2021

Associations between diabetes and sex with peritoneal dialysis technique and patient survival: Results from the Australia and New Zealand Dialysis and Transplant Registry cohort study.

Perit Dial Int 2021 01 22;41(1):57-68. Epub 2020 Apr 22.

Department of Renal Medicine, 5728Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.

Background: A differential association between mortality and cause of end-stage kidney disease in patients with type 2 diabetes mellitus (T2DM) has been shown. Sex-specific differences in diabetes-related complications have been described. It is unclear whether sex affects the associations between diabetes and peritoneal dialysis (PD) technique and patient survival.

Methods: Using the Australia and New Zealand Dialysis and Transplant Registry, we examined a two-way interaction between sex and diabetes status (no diabetes, T2DM and non-diabetic nephropathy [T2DM + non-DN] and T2DM and diabetic nephropathy [T2DM + DN]) for PD technique failure (including death), all-cause mortality and cause-specific mortality in incident adult PD patients between 1996 and 2016 using adjusted Cox regression. Mediation analysis was conducted to determine whether peritonitis was a mediator in these associations.

Results: In 8279 PD patients, those with T2DM + DN had the greatest risks in technique failure, all-cause mortality and cause-specific mortality followed by patients with T2DM + non-DN, then patients without diabetes. Sex modified the association with diabetes status in technique failure (  = 0.001) and cardiac mortality (  = 0.008). In women with T2DM + DN, the adjusted hazard ratio (HR) for technique failure was 1.45 (1.30-1.62) and was higher than men with T2DM + DN (1.17 [1.08-1.28]; referent: no diabetes). In women with T2DM + DN, the adjusted HR for cardiac mortality was 2.12 (1.73-2.61) and was also higher than men with T2DM + DN (1.66 [1.43-1.95]). Less than 10 % of the effect between diabetes and PD technique failure or mortality was mediated by peritonitis.

Conclusions: PD patients with diabetic nephropathy had increased risk of PD technique failure and mortality, with the magnitude of these risks greater in women.
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http://dx.doi.org/10.1177/0896860820918708DOI Listing
January 2021

Platelet-Rich Plasma for Hair Restoration.

Facial Plast Surg Clin North Am 2020 May 2;28(2):181-187. Epub 2020 Mar 2.

Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA. Electronic address:

Platelet-rich plasma (PRP) is a promising treatment for hair restoration in patients with androgenic alopecia. Created from a platelet concentrate from an autologous blood draw, PRP is a safe therapeutic option for patients with hair loss. It is used alone or in conjunction with topical and oral therapies. Most studies of hair restoration with PRP report positive outcomes. Further research to optimize PRP preparation/administration procedures and identify patient populations that benefit most from this treatment are needed, as is long-term follow-up of objective hair loss outcomes. PRP appears to be a safe technology with excellent potential for promoting hair restoration.
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http://dx.doi.org/10.1016/j.fsc.2020.01.009DOI Listing
May 2020

Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study.

Lancet Digit Health 2020 04 20;2(4):e201-e208. Epub 2020 Feb 20.

Division of International Epidemiology and Population Studies, Fogarty International Center, US National Institutes of Health, Bethesda MD, USA. Electronic address:

Background: As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks.

Methods: In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time.

Findings: We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35-60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020.

Interpretation: News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions.

Funding: Fogarty International Center, US National Institutes of Health.
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http://dx.doi.org/10.1016/S2589-7500(20)30026-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158945PMC
April 2020

Impact of adjuvant radiotherapy on the survival of women with optimally resected stage III endometrial cancer in the era of modern radiotherapy: a retrospective study.

Radiat Oncol 2020 Apr 6;15(1):72. Epub 2020 Apr 6.

Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

Background: The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy.

Methods: We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models.

Results: One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy.

Conclusions: Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer.

Trial Registration: ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.
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http://dx.doi.org/10.1186/s13014-020-01523-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137232PMC
April 2020

Interferon-complement loop in transplant-associated thrombotic microangiopathy.

Blood Adv 2020 03;4(6):1166-1177

Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Transplant-associated thrombotic microangiopathy (TA-TMA) is an important cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The complement inhibitor eculizumab improves TA-TMA, but not all patients respond to therapy, prompting a search for additional targetable pathways of endothelial injury. TA-TMA is relatively common after HSCT and can serve as a model to study mechanisms of tissue injury in other thrombotic microangiopathies. In this work, we performed transcriptome analyses of peripheral blood mononuclear cells collected before HSCT, at onset of TA-TMA, and after resolution of TA-TMA in children with and without TA-TMA after HSCT. We observed significant upregulation of the classical, alternative, and lectin complement pathways during active TA-TMA. Essentially all upregulated genes and pathways returned to baseline expression levels at resolution of TA-TMA after eculizumab therapy, supporting the clinical practice of discontinuing complement blockade after resolution of TA-TMA. Further analysis of the global transcriptional regulatory network showed a notable interferon signature associated with TA-TMA with increased STAT1 and STAT2 signaling that resolved after complement blockade. In summary, we observed activation of multiple complement pathways in TA-TMA, in contrast to atypical hemolytic uremic syndrome (aHUS), where complement activation occurs largely via the alternative pathway. Our data also suggest a key relationship between increased interferon signaling, complement activation, and TA-TMA. We propose a model of an "interferon-complement loop" that can perpetuate endothelial injury and thrombotic microangiopathy. These findings open opportunities to study novel complement blockers and combined anti-complement and anti-interferon therapies in patients with TA-TMA and other microangiopathies like aHUS and lupus-associated TMAs.
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http://dx.doi.org/10.1182/bloodadvances.2020001515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094010PMC
March 2020

Otopathology in CHARGE syndrome.

Laryngoscope Investig Otolaryngol 2020 Feb 13;5(1):157-162. Epub 2020 Jan 13.

Department of Otolaryngology Harvard Medical School Boston Massachusetts.

Postmortem temporal bone computed tomography (CT) and histopathologic findings in an infant with CHARGE syndrome revealed bilateral cochleovestibular hypoplasia, including cochlear pathology relevant to cochlear implant candidacy. Both ears had absence of the superior semicircular canals (SCCs), severely hypoplastic posterior SCCs, and hypoplastic (right ear) or absent (left ear) lateral SCCs seen on CT and histopathology. Histopathology further revealed the absence of all SCC ampullae except the right lateral SCC ampulla and atrophic vestibular neuroepithelium in the saccule and utricle bilaterally. The right cochlea consisted of a basal turn with patent round window, and malformed middle turn (type IV cochlear hypoplasia), with a small internal auditory canal (IAC) but near normal cochlear nerve aperture (fossette). Quantification of spiral ganglion neurons (SGNs) on histologic sections revealed a reduced SGN population (35% of normal for age), but this ear would still have likely achieved benefit from a cochlear implant based on this population. The left cochlea consisted of only a basal turn with patent round window (type III cochlear hypoplasia) with a small IAC and very small cochlear nerve aperture. Notably, histology revealed that there were no SGNs in the cochlea, and therefore, this ear would not have been a good candidate for cochlear implantation.

IV.
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http://dx.doi.org/10.1002/lio2.347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042646PMC
February 2020