Publications by authors named "Catherine Liu"

263 Publications

Infection related mortality in adults and children undergoing allogeneic hematopoietic cell transplantation: An Australian registry report.

Transplant Cell Ther 2021 Jun 7. Epub 2021 Jun 7.

National Centre for Infection in Cancer, Peter MacCallum Cancer Centre, Melbourne, Australia; Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.

Background: Infection related mortality (IRM) is the most common non-relapse mortality reported post allogeneic hematopoietic cell transplantation (HCT). Information on the incidence and timing of specific infective organisms and the risk factors for IRM is essential to developing prevention strategies.

Objective: This report provides the first account of IRM in adults and children undergoing HCT in Australia.

Study Design: Between 2013 and 2018, 2705 adult and 689 pediatric first HCTs were identified from the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) database, with 1075 (39.7%) total overall deaths in adults and 134 (19.4%) in children. Demographics and causes of death including infectious etiology and causative organisms were extracted from the database for adults and children for analysis.

Results: At day 100 and 1-year post-HCT, IRM was the leading cause of early post-HCT mortality in adults, accounting for 6.2% and 9.8%, respectively; in children IRM was the leading cause of post-HCT mortality at day 100 at 2.5%, and the second highest cause of post-HCT mortality at 1-year post-HCT at 4.9%, following relapse at 5.8%. In adults, older age, transplantation not in a first complete remission (non-CR1), the use of ATG or alemtuzumab, CMV serostatus D+/R- and acute Graft Versus Host Disease (aGVHD) were significant risk factors for IRM. However, in children, age >5 years old, Acute Lymphocytic Leukemia (ALL) primary disease and mismatched unrelated or haploidentical donor sources predicted IRM. Of the deaths where an infectious etiology was reported in adults (52.4%), 49.3% were attributed to bacteria, 25.3% to fungus, 21.7% to viruses, and 3.6% to Post-Transplant Lymphoproliferative Disorder (PTLD). The most common organisms were Pseudomonas spp., Enterococcus spp., Candida spp., Aspergillus spp. and cytomegalovirus (CMV). In children where an infectious etiology was reported (64%), 13% were attributed to bacteria, 26% to fungus, 45% to viruses, and 16% to PTLD.

Conclusions: This report highlights that IRM was the leading cause of death early post-HCT in Australia. Strategies to reduce IRM, such as individualized pre-transplant infection risk assessment, rapid diagnostics and prevention management strategies should be explored to determine if these outcomes can be improved. In addition, improving the completeness and accuracy of reported data, particularly the infectious pathogens, could assist in directing management strategies to reduce IRM in HCT.
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http://dx.doi.org/10.1016/j.jtct.2021.05.028DOI Listing
June 2021

ZFP36L1 plays an ambiguous role in the regulation of cell expansion and negatively regulates CDKN1A in chronic myeloid leukemia cells.

Exp Hematol 2021 Jun 3. Epub 2021 Jun 3.

Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel Germany.

The mRNA-destabilizing proteins ZFP36L1 and ZFP36L2 are described to be mediators of quiescence and play a pivotal role in hematopoietic malignancies. Both genes are mainly classified as tumor suppressor genes as they posttranscriptionally downregulate the expression of oncogenes and contribute to cellular quiescence. Here, we analyzed the role of ZFP36L1 and ZFP36L2 in chronic myeloid leukemia (CML). We found ZFP36L1 and ZFP36L2 expression to be deregulated in CML patients. By using in vitro models of tyrosine kinase inhibitor resistance, an increase in ZFP36L1 and ZFP36L2 expression was detected during the development of imatinib resistance. CRISPR/Cas9-derived knockout of ZFP36L1, but not of ZFP36L2, in imatinib sensitive cells led to decreased proliferation rates in response to tyrosine kinase inhibitor treatment. This effect was also observed in untreated ZFP36L1 knockout cells, albeit to a lower extent. Genome-wide gene expression analyses of ZFP36L1 knockout cells revealed differential expression of cell cycle regulators, in particular upregulation of the cell cycle inhibitor CDKN1A. In addition, the 3' UTR of CDKN1A was proven to be a direct target of ZFP36L1. This shows that tumor suppressor genes can also be targeted by ZFP36L1. Hence, ZFP36L1 cannot unambiguously be regarded as tumor suppressor genes.
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http://dx.doi.org/10.1016/j.exphem.2021.05.006DOI Listing
June 2021

Cytomegalovirus Blepharitis and Keratitis Masquerading as Eyelid Malignancy.

Ophthalmic Plast Reconstr Surg 2021 Jun 4. Epub 2021 Jun 4.

UC San Diego Viterbi Family Department of Ophthalmology Division of Oculofacial Plastic and Reconstructive Surgery, UC San Diego Viterbi Family Department of Ophthalmology, Shiley Eye Institute, La Jolla, California, U.S.A.

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http://dx.doi.org/10.1097/IOP.0000000000001992DOI Listing
June 2021

Outcomes of Single Suture Mueller's Muscle Conjunctival Resection: Ethnic Considerations.

Ophthalmic Plast Reconstr Surg 2021 Jun 4. Epub 2021 Jun 4.

Department of Ophthalmology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang, Gyeonggido, Korea Division of Oculofacial Plastic and Reconstructive Surgery, Viterbi Family Department of Ophthalmology, UC San Diego Shiley Eye Institute, La Jolla, California, U.S.A. Division of Plastic Surgery, UC San Diego, La Jolla, California, U.S.A.

Purpose: To compare outcomes of Mueller's Muscle Conjunctival Resection (MMCR) between 2 groups of patients with different anatomy due to ethnic heritage.

Methods: The medical records of patients who underwent MMCR between 2013 and 2018 were retrospectively reviewed. Patients who underwent additional procedures, such as upper blepharoplasty and browplasty, were excluded from the study. Patients were divided in 2 groups based on self-identified ethnic groups (Asian and Caucasian). Image J software was used to calculate MRD1 from digital images. The improvement of MRD1 (net MRD1) after surgery was evaluated and compared between 2 groups.

Results: Eighty-three eyes of 68 patients were included in this study. The Asian group consisted of 41 eyelids from 28 patients. The Caucasian group consisted of 42 eyelids from 40 patients. The average age was 52.18 (SD 20.176) in the Asian group compared with the 66.45 years (SD 9.22, p< 0.005) in the Caucasian group. The mean improvement of MRD1 was 1.96 ± 0.75 mm in Asian group and 2.05 ± 0.72 mm in Caucasian group, which was not statistically significant (p = 0.62). The incidence of ptosis overcorrection and undercorrection between the groups was also not statistically significant.

Conclusions: There was no statistically significant difference in the surgical outcomes among the 2 study groups. Despite differences in the anatomy of Caucasian and Asian eyelids, MMCR is a successful procedure in patients self-identified from both ethnic groups.
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http://dx.doi.org/10.1097/IOP.0000000000001980DOI Listing
June 2021

Teprotumumab for chronic thyroid eye disease.

Orbit 2021 Jun 1:1-8. Epub 2021 Jun 1.

Division of Oculofacial Plastic and Reconstructive Surgery, UC San Diego Viterbi Family Department of Ophthalmology, Shiley Eye Institute, La Jolla, California, USA.

: To describe the treatment of nine patients with chronic, low clinical activity score thyroid eye disease with teprotumumab.: A retrospective series of patients with chronic thyroid eye disease (TED) and low clinical activity score (CAS) treated with teprotumumab infusion therapy. Inclusion criteria: adults over 18 years of age with TED for greater than 9 months and CAS of 1 or less. All patients included in the analyses completed a full series of eight infusions. Primary outcome measures included proptosis and eyelid retraction in both eyes. Secondary outcomes included CAS, reported adverse effects, and surgery post-treatment.: Nine patients met all inclusion criteria, seven females and two males with mean age of 50.2 years and TED diagnosis of 6.25 years. Three patients had a baseline CAS of 1 and 6 had a CAS of 0. Mean proptosis reduction in the worse eye was 4.0 ± 2.4 mm immediately post-treatment ( = .02). Five out of nine patients had extended follow-up (average 16.8 ± 5.1 weeks) with mean proptosis reduction of 4.2 ± 2.8 mm at last follow-up ( = .03). Mean reduction in eyelid retraction in the worse eye was 0.3 ± 1.6 mm post-treatment ( = .58) and 0.5 ± 0.9 mm at last follow-up ( = .30). Three patients reported infusion-related myalgias, two hair thinning, one exacerbated chronic tinnitus, and one hyperglycemia.: We report clinically and statistically significant proptosis reduction in nine patients with chronic, low CAS TED treated with teprotumumab. Teprotumumab may be an effective treatment option for these patients.
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http://dx.doi.org/10.1080/01676830.2021.1933081DOI Listing
June 2021

Minimal Dissection Direct Frontalis Muscle Advancement Flap for Congenital Ptosis Repair.

J Craniofac Surg 2021 May 28. Epub 2021 May 28.

Division of Oculofacial Plastic and Reconstructive Surgery, University of California San Diego Viterbi Family Department of Ophthalmology School of Medicine, University of California San Diego, Division of Plastic and Reconstructive Surgery, University of California San Diego Department of Surgery, La Jolla, CA.

Background: Frontalis flap advancement is an alternative means of congenital ptosis repair from frontalis suspension utilizing autologous fascia or allogenic implants. Variations in technique, including flap division, location and number of skin incisions, and dissection planes, are described in the literature.

Materials And Methods: A retrospective case series of patients with congenital myogenic ptosis treated with simplified, minimal dissection frontalis flap advancement involving a single upper eyelid crease incision with dissection in the preseptal and subcutaneous planes without division to mobilize the frontalis flap. Inclusion criteria: pediatric patients age < 18 years with either primary or recurrent congenital ptosis following previous surgical repair. Exclusion criteria: ptosis of neurogenic etiology or postoperative follow-up < 3 months. Primary outcome measures were postoperative margin-reflex distance 1 (MRD1), the difference in MRD1 between surgical and nonsurgical eyelids in unilateral ptosis, and lagophthalmos. Secondary outcome measures included recurrence and complications.

Results: Twenty-six patients met inclusion criteria, 24 males and 2 females. Mean postoperative MRD1 at last follow-up was 2.9 ± 1.2 mm and the mean difference in MRD1 between surgical and nonsurgical eyelids at last follow-up was 1.1 ± 1.0 mm. Average lagophthalmos at postoperative month 2 to 5 was 0.6 ± 0.7 mm. One patient demonstrated postoperative lid retraction that required re-operation. Four of 31 eyelids (12.9%) demonstrated ptosis recurrence at 5, 12, or 24 months.

Conclusions: In this retrospective series, the authors report clinically and statistically significant surgical eyelid height improvement and symmetry between nonsurgical and surgical eyelids in congenital ptosis patients treated with minimal dissection direct frontalis flap advancement.
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http://dx.doi.org/10.1097/SCS.0000000000007761DOI Listing
May 2021

Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity is required for V(D)J recombination.

J Exp Med 2021 Aug 25;218(8). Epub 2021 May 25.

Department of Medicine, Division of Hematology and Oncology, University of Alabama at Birmingham School of Medicine, Birmingham, AL.

A whole-genome CRISPR/Cas9 screen identified ATP2A2, the gene encoding the Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2 protein, as being important for V(D)J recombination. SERCAs are ER transmembrane proteins that pump Ca2+ from the cytosol into the ER lumen to maintain the ER Ca2+ reservoir and regulate cytosolic Ca2+-dependent processes. In preB cells, loss of SERCA2 leads to reduced V(D)J recombination kinetics due to diminished RAG-mediated DNA cleavage. SERCA2 deficiency in B cells leads to increased expression of SERCA3, and combined loss of SERCA2 and SERCA3 results in decreased ER Ca2+ levels, increased cytosolic Ca2+ levels, reduction in RAG1 and RAG2 gene expression, and a profound block in V(D)J recombination. Mice with B cells deficient in SERCA2 and humans with Darier disease, caused by heterozygous ATP2A2 mutations, have reduced numbers of mature B cells. We conclude that SERCA proteins modulate intracellular Ca2+ levels to regulate RAG1 and RAG2 gene expression and V(D)J recombination and that defects in SERCA functions cause lymphopenia.
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http://dx.doi.org/10.1084/jem.20201708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155808PMC
August 2021

Geographic Access Disparities to Clinical Trials in Retinopathy of Prematurity in the United States.

Retina 2021 May 13. Epub 2021 May 13.

Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, PA.

Purpose: To identify geographic and socioeconomic variables predictive of residential proximity to retinopathy of prematurity (ROP) clinical trial locations.

Methods: This cross-sectional epidemiological study employed census-tract level data from 3 national public datasets and trial-level data from ClinicalTrials.gov. Socioeconomic predictors of driving distance and time to the nearest ROP clinical trial location were identified. Primary outcomes were time >60 minutes and distance >60 miles traveled to the nearest ROP clinical trial.

Results: Multivariate analysis showed that residents were more likely to travel >60 minutes to the nearest ROP clinical trial if they lived in census tracts that were rural [adjusted odds ratio (aOR) 1.20, (P = 0.0002], had higher percentages of the population living ≤ federal poverty level (4th Quartile vs 1st Quartile, aOR 1.19, P < 0.0001), or had less education (Associates vs. Bachelor's degree, aOR 1.01 , P <0.007). In contrast, counties with higher percentages of births <1500g (aOR 0.88, P = 0.0062) were less likely to travel >60 minutes. Similar variables predicted travel distance.

Conclusions: Although counties with higher incidences of very-low birth weight infants were closer to ROP clinical trial sites, residents living in rural and low-income census tracts had significantly greater travel burdens.
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http://dx.doi.org/10.1097/IAE.0000000000003218DOI Listing
May 2021

Outcomes of Hematopoietic Cell Transplantation in Patients with Mixed Response to Pretransplantation Treatment of Confirmed or Suspected Invasive Fungal Infection.

Transplant Cell Ther 2021 May 5. Epub 2021 May 5.

Department of Medicine, University of Washington, Seattle, Washington; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Patients with hematologic malignancy or bone marrow failure are typically required to achieve radiographic improvement or stabilization of invasive fungal infection (IFI) before hematopoietic cell transplantation (HCT) owing to a concern for progression before engraftment. Refractory IFI with a mixture of improvement and progression on serial imaging (ie, mixed response) poses a clinical dilemma, because a delay in HCT may allow for a hematologic relapse or other complications. Furthermore, HCT itself may yield the immune reconstitution necessary for clearance of infection. We sought to describe the characteristics and outcomes of patients who underwent HCT with mixed response IFI. We performed a chart review of all patients who underwent HCT between 2014 and 2020 in whom imaging within 6 weeks before HCT indicated a mixed response to treatment of a diagnosed IFI. Fourteen patients had evidence of a mixed response in low-to-moderate burden of diagnosed IFI by imaging before HCT, including 9 with pulmonary aspergillosis, 2 with hepatosplenic candidiasis (1 also with aspergillosis), and 4 with pulmonary nodules of presumed fungal etiology. Five had refractory severe neutropenia at evaluation for HCT (median, 95 days). All 14 patients showed radiographic stability or improvement in imaging following engraftment; no IFI-related surgeries were required, and no IFI-related deaths occurred. For patients without relapse who underwent HCT more than 1 year earlier, 7 of 8 (88%) were alive at 1 year. Our findings suggest that low-to-moderate burden IFI with mixed response is unlikely to progress on appropriate therapy before engraftment during allogeneic HCT.
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http://dx.doi.org/10.1016/j.jtct.2021.04.021DOI Listing
May 2021

Development and Validation of a Machine Learning Model to Estimate Bacterial Sepsis Among Immunocompromised Recipients of Stem Cell Transplant.

JAMA Netw Open 2021 Apr 1;4(4):e214514. Epub 2021 Apr 1.

Department of Epidemiology, University of Washington, Seattle.

Importance: Sepsis disproportionately affects recipients of allogeneic hematopoietic cell transplant (allo-HCT), and timely detection is crucial. However, the atypical presentation of sepsis within this population makes detection challenging, and existing clinical sepsis tools have limited prognostic value among this high-risk population.

Objective: To develop a full risk factor (demographic, transplant, clinical, and laboratory factors) and clinical factor-specific automated bacterial sepsis decision support tool for recipients of allo-HCT with potential bloodstream infections (PBIs).

Design, Setting, And Participants: This prognostic study used data from adult recipients of allo-HCT transplanted at the Fred Hutchinson Cancer Research Center, Seattle, Washington, between June 2010 and June 2019 randomly divided into 70% modeling and 30% validation data sets. Tools were developed using the area under the curve (AUC) optimized SuperLearner, and their performance was compared with existing clinical sepsis tools: National Early Warning Score (NEWS), quick Sequential Organ Failure Assessment (qSOFA), and Systemic Inflammatory Response Syndrome (SIRS), using the validation data set. Data were analyzed between January and October of 2020.

Main Outcomes And Measures: The primary outcome was high-sepsis risk bacteremia (culture confirmed gram-negative species, Staphylococcus aureus, or Streptococcus spp bacteremia), and the secondary outcomes were 10- and 28-day mortality. Tool discrimination and calibration were examined using accuracy metrics and expected vs observed probabilities.

Results: Between June 2010 and June 2019, 1943 recipients of allo-HCT received their first transplant, and 1594 recipients (median [interquartile range] age at transplant, 54 [43-63] years; 911 [57.2%] men; 1242 individuals [77.9%] identifying as White) experienced at least 1 PBI. Of 8131 observed PBIs, 238 (2.9%) were high-sepsis risk bacteremia. Compared with high-sepsis risk bacteremia, the full decision support tool had the highest AUC (0.85; 95% CI, 0.81-0.89), followed by the clinical factor-specific tool (0.72; 95% CI, 0.66-0.78). SIRS had the highest AUC of existing tools (0.64; 95% CI, 0.57-0.71). The full decision support tool had the highest AUCs for PBIs identified in inpatient (0.82; 95% CI, 0.76-0.89) and outpatient (0.82; 95% CI, 0.75-0.89) settings and for 10-day (0.85; 95% CI, 0.79-0.91) and 28-day (0.80; 95% CI, 0.75-0.84) mortality.

Conclusions And Relevance: These findings suggest that compared with existing tools and the clinical factor-specific tool, the full decision support tool had superior prognostic accuracy for the primary (high-sepsis risk bacteremia) and secondary (short-term mortality) outcomes in inpatient and outpatient settings. If used at the time of culture collection, the full decision support tool may inform more timely sepsis detection among recipients of allo-HCT.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.4514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056279PMC
April 2021

Citation of prior systematic reviews in reports of randomized controlled trials published in dental speciality journals.

J Dent 2021 Jun 6;109:103658. Epub 2021 Apr 6.

Department of Orthodontics and Dentofacial Orthopedics, Dental School/Medical Faculty, University of Bern, Switzerland.

Objectives: To assess the extent to which reports of dental Randomised Clinical Trials (RCTs) cite prior systematic reviews (SR) to explain the rationale or justification of the trial. Study characteristics that predicated the citation of SR in the RCT report were explored.

Methods: An electronic database search was undertaken to identify dental RCTs published between 1st January 2014 and 31st December 2019. All titles and abstracts were screened independently by two authors. Descriptive statistics and associations were calculated for the study characteristics. Logistic regression was used to identify predicators of SR inclusion in the trial report.

Results: 682 RCTs were analysed. 312 SRs were available of which 62.5 % were cited and 37.5 % were not included but were available in the literature within 12 months of trial commencement. An association between inclusion of SR and trial registration (P = 0.046) was detected. For the inclusion of a SR, authors based in Asia or other had lower odds than those based in Europe (OR: 0.53; 95 % CI:0.34,0.82; p = 0.005). Every unit increase in journal impact factor increased the odds of SR inclusion (OR: 1.23; 95 %: 1.06, 1.43; p = 0.006).

Conclusions: A relatively high proportion of dental RCTs (37.5 %) did not cite a SR in the introduction section to justify the rationale of the trial when a relevant SR was available. Trials conducted by a corresponding author based in Europe and published in journals with an increasing impact factor were also more likely to cite a SR.

Clinical Significance: Further progress is required to minimise research waste and ensure resources are channelled towards clinically useful trials which have an appropriate rationale and justification.
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http://dx.doi.org/10.1016/j.jdent.2021.103658DOI Listing
June 2021

Validity of 2020 vancomycin consensus guidelines and further guidance for practical application.

Am J Health Syst Pharm 2021 Mar 25. Epub 2021 Mar 25.

University of Arkansas for Medical Sciences College of Pharmacy & Arkansas Children's Hospital Little Rock, AR.

In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
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http://dx.doi.org/10.1093/ajhp/zxab123DOI Listing
March 2021

Rare case of pancrelipase therapy-induced neutropaenia.

BMJ Case Rep 2021 Mar 22;14(3). Epub 2021 Mar 22.

Internal Medicine, Allegheny Health Network, Pittsburgh, Pennsylvania, USA.

A 61-year-old man was transferred to our facility from an outside hospital due to refractory neutropaenia of unknown aetiology. The patient presented to the referring hospital with a 5-day history of worsening diarrhoea and abdominal pain. Initial lab results at presentation showed severe neutropaenia with an absolute neutrophil count of 0. Investigations included a bone marrow biopsy which showed slightly hypocellular marrow with near absence of granulocytic precursors. A CT without contrast showed evidence of chronic pancreatitis and acute colitis. The patient's neutropaenia persisted despite granulocyte colony-stimulating factor therapy. The patient was, thus, transferred to our facility for a higher level of care. At our facility, the patient had rapid correction of neutropaenia after discontinuation of pancrelipase therapy. The patient's abdominal pain and diarrhoea also improved while off pancrelipase. Neutropaenia has completely resolved 6 weeks after discharge without any further therapy.
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http://dx.doi.org/10.1136/bcr-2021-241799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986883PMC
March 2021

Secondary infection with rhino-orbital cerebral mucormycosis associated with COVID-19.

Orbit 2021 Mar 23:1-4. Epub 2021 Mar 23.

Division of Oculofacial Plastic and Reconstructive Surgery, Viterbi Family Department of Ophthalmology, UC San Diego Shiley Eye Institute, La Jolla, California, USA.

We report two fatal cases of rhino-orbital-cerebral mucormycosis associated with COVID-19 infection. Both patients had pre-existing diabetes mellitus type 2, were treated with corticosteroids, and developed ketoacidosis. Both patients rapidly declined owing to rapid extension of the infection into the intracranial cavity. We postulate that additional risk factors for opportunistic fungal infection exist in COVID-19 patients including mechanical ventilation and Sars-CoV-2 induced immunosuppression. The ophthalmologist's role is particularly important in the early diagnosis of mucormycosis associated with COVID-19.
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http://dx.doi.org/10.1080/01676830.2021.1903044DOI Listing
March 2021

Development of a dual delivery of levofloxacin and prednisolone acetate via PLGA nanoparticles/ thermosensitive chitosan-based hydrogel for postoperative management: An in-vitro and ex-vivo study.

Int J Biol Macromol 2021 Jun 4;180:365-374. Epub 2021 Mar 4.

Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Faculty of Medicine, Taipei, Taiwan. Electronic address:

Post-operative endophthalmitis (POE) is one of the most dreadful complications after intraocular surgery. For cataract surgery patients, both commercially available topical 0.5% levofloxacin and 1% prednisolone acetate (PA) ophthalmic solution require at least 3 to 4 times application daily. In this study, we develop a dual drug delivery system composed of the thermosensitive chitosan/gelatin-based hydrogel containing PA and levofloxacin-loaded nanoparticles (LNPs). LNPs with negative surface charge show the monodisperse (polydispersity index ~0.045), nanosize (~154.7 nm) and sphere-like structure. The optimal concentration of LNPs and PA to corneal epithelial cells was 5 μg/mL and 50 μg/mL, respectively. The developed dual drug delivery system (PAgel-LNPs) could gel at 34 °C within 63 s. The osmolarity of PAgel-LNPs was 301.2 ± 1.5 mOsm/L. PAgel-LNPs showed a sustained-release profile for 7 days. Post-treatment of PAgel-LNPs in TNF-α-damaged corneal epithelial cells could decrease the inflammation (inflammatory genes (TNF-α, IL-6, MMP-3 andMMP-9) and IL-6 production) and cell death. In ex-vivo rabbit model of S. aureus keratitis, the anti-inflammation and anti-bacterial property have been demonstrated. These results suggest that thermosensitive PAgel-LNPs may have the potential to use for the prevention of POE.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.017DOI Listing
June 2021

Corneal neurotization for neurotrophic keratopathy: Review of surgical techniques and outcomes.

Ocul Surf 2021 Apr 26;20:163-172. Epub 2021 Feb 26.

Illinois Eye and Ear Infirmary, Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.

Neurotrophic keratopathy is a degenerative disease in which damage to the corneal nerves leads to corneal hypoesthesia. Injuries to neurotrophic corneas are notoriously difficult to treat and have traditionally been approached with supportive management. However, recent progress in the field of corneal neurotization has given new direction for addressing nerve loss directly by stimulating new nerve growth onto the cornea from nearby sensory nerves transferred to the perilimbal region. Herein, we review the surgical techniques utilized in corneal neurotization, including direct transfers and the use of nerve grafts. Considerations in surgical approach, as well as factors that influence prognosis and outcomes of the surgical intervention are also discussed.
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http://dx.doi.org/10.1016/j.jtos.2021.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113161PMC
April 2021

Comparison of the iCare, Tono-Pen, non-contact airpuff, and Goldmann applanation tonometers in eyes with corneal edema after penetrating keratoplasty.

J Chin Med Assoc 2021 Mar;84(3):320-325

Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Background: To compare the utility of the iCare, Tono-Pen, and non-contact airpuff (NCT) tonometers with the Goldmann applanation tonometer (GAT) for measuring intraocular pressure (IOP) in patients with corneal edema after penetrating keratoplasty (PKP) and to assess the effects of central corneal thickness (CCT) and corneal curvature (CC) on IOP measurements.

Methods: Thirty-two eyes of 27 patients with corneal edema after PKP due to corneal abnormalities and 43 control eyes of 30 patients with normal corneas were recruited. Before IOP measurements, all patients underwent a baseline examination, including auto-refraction, keratometry, slit lamp biomicroscopy, and CCT measurement. IOP was measured using the devices in the same order: first the NCT, followed by the iCare, Tono-Pen, and GAT. The differences between the iCare, Tono-Pen, NCT, and GAT were calculated with repeated-measures analysis of variance. The Bland-Altman method was used to assess the agreement between the iCare, Tono-Pen, and NCT versus the GAT. The influences of CCT and CC on IOP measurement were evaluated by correlation analysis using Pearson's correlation coefficient.

Results: Mean IOP measurements were significantly higher with the NCT and Tono-Pen than with the GAT in the PKP and control groups. When compared with GAT, iCare showed significantly higher IOP readings in the control group, but the IOP readings did not differ between the iCare and GAT in the PKP group. Poor agreement was noted between the NCT and GAT in both groups. The Tono-Pen showed clinically acceptable agreement with GAT in control eyes and poor agreement in PKP eyes. The agreement between the iCare and GAT appeared to be clinically acceptable in both groups. Correlation analysis of the results from control eyes showed that the IOP measurements with the GAT and NCT were weakly related to CCT and moderately correlated with CC. The iCare IOP readings were weakly correlated with CCT and CC.

Conclusion: In the PKP group, the NCT and Tono-Pen significantly overestimated IOP, whereas the iCare IOP readings were similar to those obtained using the GAT. Poor agreement was noted between the NCT and GAT as well as between the Tono-Pen and GAT, but the iCare showed clinically acceptable agreement with GAT. In normal corneas, the GAT, NCT, and iCare were affected by CCT and CC. The iCare tonometer was less affected by corneal edema than were the NCT and the Tono-Pen. The iCare appears to be a useful device for IOP measurement in eyes with corneal edema after PKP.
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http://dx.doi.org/10.1097/JCMA.0000000000000476DOI Listing
March 2021

Cytomegalovirus (CMV) management in allogeneic hematopoietic cell transplantation: Pre-transplant predictors of survival, reactivation, and spontaneous clearance.

Transpl Infect Dis 2020 Dec 20:e13548. Epub 2020 Dec 20.

Haematology Department, Royal North Shore Hospital, Sydney, Australia.

Background: Cytomegalovirus (CMV) reactivation is a frequent complication after allogeneic hematopoietic cell transplant (alloHCT).

Method: We analyzed 159 alloHCT recipients with 4409 quantitative CMV viral loads to determine pre-transplant predictors of CMV reactivation, clinically significant CMV infection (cs-CMVi, defined as CMV viral load >1000 IU/mL), CMV disease, kinetics of spontaneous clearance of CMV, and survival using a standardized pre-emptive therapy approach to identify at-risk groups to target prevention strategies.

Results: Cs-CMVi was most common in D-/R+ unrelated donor transplants (URD). Spontaneous CMV clearance occurred in 26% of patients who reached a viral load of 56-137 IU/mL, 6% at 138-250 IU/mL and in one patient >250 IU/mL. Median time between the first CMV reactivation (>56 IU/mL) and a viral load >250 IU/mL was 13 days, whereas the time from the first viral load >250 IU/mL to reach a vial load >1000 IU/mL was 4 days. Cs-CMVi was associated with a significant increase in non-relapse mortality (NRM) on multivariate analysis.

Conclusions: Overall, this study indicates that D-/R+ URD recipients are at high-risk for cs-CMVi- and CMV-related mortality, and are potential candidates for targeted CMV prophylaxis. Spontaneous clearance of CMV beyond a viral load of 250 IU/mL is uncommon, suggesting that this could be used as an appropriate threshold to initiate pre-emptive therapy.
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http://dx.doi.org/10.1111/tid.13548DOI Listing
December 2020

Association between dry eye and depressive symptoms in an elderly Chinese population in Taiwan: the Shihpai Eye Study.

Eye (Lond) 2020 Nov 30. Epub 2020 Nov 30.

Community Medicine Research Center and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.

Background: Dry eye may impact quality of life and daily activities and depression is a widespread illness. Many studies showed the two diseases often coexist. However, studies were limited to retrospective chart review. This study aimed to investigate the association between dry eye and depressive symptoms in an older Asian population.

Methods: The Shihpai Eye Study was a community-based, cross-sectional survey of vision and eye diseases among noninstitutionalized subjects 65 years of age and older in Shihpai, Taipei, Taiwan. Residents fulfilling these criteria were randomly selected to be invited to participate in the study, which included a questionnaire and an eye examination conducted between July 1, 1999 and December 31, 2000.

Results: Of the 2045 subjects recruited, 1361 (66.6%) completed the examination. 8.8% (95% confidence interval (CI): 7.3-10.3%) of the participants were diagnosed to have depressive symptoms. Under multivariate analysis, depressive symptoms were significantly associated with frequent symptoms of dry eye (odds ratio (OR): 1.97, 95% CI: 1.36-2.92; p < 0.001). None of the dry eye signs was associated with depressive symptoms. For participants reporting frequent symptoms, tear-film break-up time ≤ 10 s (OR: 2.06, 95% CI: 1.38-3.05; p < 0.001), Schirmer test score ≤ 5 mm (OR: 2.01, 95% CI: 1.33-3.03; p < 0.001), and meibomian gland disease (OR: 1.99, 95% CI: 1.31-3.01; p = 0.001) were significantly related to depressive symptoms. Fluorescein staining of the cornea was not correlated to depressive symptoms in participants with dry eye symptoms.

Conclusions: Depressive symptoms are more highly correlated with dry eye symptoms than dry eye signs.
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http://dx.doi.org/10.1038/s41433-020-01329-5DOI Listing
November 2020

Predictors of treatment decisions made by adult orthodontic patients presenting with unerupted permanent teeth.

Int Orthod 2021 Mar 25;19(1):76-81. Epub 2020 Nov 25.

Guy's hospital, Guy's and Saint-Thomas NHS Foundation Trust, King's college London, faculty of dentistry, oral and craniofacial sciences, department of orthodontics, floor 25, SE1 9RT London, United Kingdom. Electronic address:

Objective: Unerupted permanent teeth are amongst the most commonly occurring dental anomalies in adults and present unique treatment challenges. The aim of this retrospective study was to (1) identify the prevalence of adult patients with unerupted teeth attending a multidisciplinary clinic and (2) to identify predictors (age, gender, incisor and skeletal classification) which influence the patients treatment decision.

Material And Methods: Consecutive adult patients with unerupted permanent teeth attending the Joint Orthodontic-Restorative clinic were identified. Study variables were collected using a prespecified data collection form. Descriptive statistics were employed; Fisher's exact test was used to detect associations between variables and treatment decision outcome. Ordinal logistic regression derived multinomial regression relative risk ratios (RRR) and 95% confidence intervals (CI) were calculated for the effect of age, gender, incisor and skeletal classification on treatment decision/outcome.

Results: Sixty-six patients with impacted teeth were identified from a sample of 483. The prevalence of adults with unerupted teeth was 13.7%. The mean age was 30.7 years (SD 11.2). The majority of the sample had a Class I incisor relationship (54.6%) or Class I skeletal base relationship (54.6%), and the most common distribution of impacted teeth was a single unerupted upper right canine (34.9%). Orthodontic treatment (non-extraction or extraction basis incorporating the alignment or removal of impacted teeth) and restorative treatment only were equally favoured. Factors including age, gender, incisor and skeletal classification did not appear to influence or predict the final treatment decision.

Conclusions: In this sample, adults presenting with impacted teeth favoured certain treatment modalities: orthodontic treatment only and restorative treatment only. Factors such as age, gender, incisor and skeletal classification did not influence the outcome.
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http://dx.doi.org/10.1016/j.ortho.2020.10.004DOI Listing
March 2021

Questions on Vancomycin dosing.

Clin Infect Dis 2020 Nov 26. Epub 2020 Nov 26.

University of Arkansas for Medical Sciences College of Pharmacy & Arkansas Children's Hospital, Little Rock, AR.

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http://dx.doi.org/10.1093/cid/ciaa1775DOI Listing
November 2020

Intravascular Papillary Endothelial Hyperplasia as a Cause of Reversible Vision Loss.

J Craniofac Surg 2020 Nov 23. Epub 2020 Nov 23.

Department of Ophthalmology and Vision Sciences.

Intravascular papillary endothelial hyperplasia (IPEH) is a benign vascular lesion that is formally diagnosed on histopathology. IPEH seldom presents in periocular tissues and is even less commonly seen deep within the orbit. As with cavernous hemangioma, this lesion tends to distort surrounding structures and can cause a significant mass effect in the orbit. The authors present an unusual case of orbital IPEH that resulted in severe proptosis and progressive vision loss from optic nerve compression. In toto surgical excision of the lesion resulted in significant recovery of vision loss and resolution of symptoms associated with proptosis. To the best of our knowledge, this case is the first to illustrate the potential for visual recovery after surgery in a patient with compressive optic neuropathy from orbital IPEH.
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http://dx.doi.org/10.1097/SCS.0000000000007271DOI Listing
November 2020

Outcomes and risk factors for failure after trabeculectomy in Taiwanese patients: medical chart reviews from 2006 to 2017.

Br J Ophthalmol 2020 Nov 23. Epub 2020 Nov 23.

Department of Ophthalmology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan

Aims: To determine long-term outcomes and risk factors for failure after mitomycin C (MMC)-augmented initial trabeculectomy (IT) in Taiwanese patients.

Methods: We reviewed medical records of patients with glaucoma undergoing IT during December 2006-December 2016. We defined complete success as an intraocular pressure (IOP) of >5 or ≤21 mm Hg or IOP reduction of ≥20% from baseline without supplemental medications and qualified success as the aforementioned IOP levels with or without supplemental medications. Kaplan-Meier survival and Cox proportional analyses evaluated success rates and risk factors for failure, respectively.

Results: We enrolled 190 patients (237 eyes; mean age: 54.0±15.3 years; mean postoperative follow-up period: 68.4±35.1 months). Mean IOP and glaucoma medications decreased from 22.2±10.8 to 14.4±5.2 mm Hg (p<0.001) and 3.0±0.7 to 1.8±1.2 (p=0.015), respectively, at the last visit. Cumulative qualified success rates were 93.9%, 93.0%, 86.5% and 67.1% at the 1, 2, 5 and 10 years follow-up, respectively; however, only 7.7% of the eyes reached complete success at the last visit. Eyes with poor preoperative visual acuity were associated with low qualified success rates (HR=1.689, p=0.027); patients aged >70 years had higher complete success rates than did those aged ≤70 years. Five cases (2.11%) exhibited bleb-associated complications.

Conclusion: Despite satisfactory long-term success rates, most eyes needed medication for IOP control, supporting the notion of predisposed scarring vitality in patients of Chinese ethnicity following MMC-augmented trabeculectomy.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317303DOI Listing
November 2020

Infectious Disease Complications in Patients with Cancer.

Crit Care Clin 2021 Jan 1;37(1):69-84. Epub 2020 Nov 1.

Division of Infectious Diseases, Department of Medicine, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.

Critically ill patients with cancer are vulnerable to infections because of the underlying malignancy, tumor-directed therapy, immunosuppression, breaches in mucosa or skin, malnutrition, and other factors. Neutropenia remains the most important risk factor for infection. Infectious complications occurring in critically ill patients with cancer can affect the bloodstream, lungs, gastrointestinal tract, central nervous system, urinary tract, and the skin. Pneumonias are the leading cause of infection in patients with cancer admitted to the intensive care unit. Consideration of opportunistic pathogens in the differential diagnosis is important in patients with impaired cellular and/or humoral immunity or compromised splenic function.
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http://dx.doi.org/10.1016/j.ccc.2020.09.001DOI Listing
January 2021

Improving Appropriate Diagnosis of Infection Through an Enteric Pathogen Order Set With Computerized Clinical Decision Support: An Interrupted Time Series Analysis.

Open Forum Infect Dis 2020 Oct 21;7(10):ofaa366. Epub 2020 Aug 21.

Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.

Background: Inappropriate testing for leads to overdiagnosis of infection (CDI). We determined the effect of a computerized clinical decision support (CCDS) order set on polymerase chain reaction (PCR) test utilization and clinical outcomes.

Methods: This study is an interrupted time series analysis comparing PCR test utilization, hospital-onset CDI (HO-CDI) rates, and clinical outcomes before and after implementation of a CCDS order set at 2 academic medical centers: University of Washington Medical Center (UWMC) and Harborview Medical Center (HMC).

Results: Compared with the 20-month preintervention period, during the 12-month postimplementation of the CCDS order set, there was an immediate and sustained reduction in PCR test utilization rates at both hospitals (HMC, -28.2% [95% confidence interval {CI}, -43.0% to -9.4%],  = .005; UWMC, -27.4%, [95% CI, -37.5% to -15.6%],  < .001). There was a significant reduction in rates of tests ordered in the setting of laxatives (HMC, -60.8% [95% CI, -74.3% to -40.1%],  < .001; UWMC, -37.3%, [95% CI, -58.2% to -5.9%],  = .02). The intervention was associated with an increase in the test positivity rate at HMC ( = .01). There were no significant differences in HO-CDI rates or in the proportion of patients with HO-CDI who developed severe CDI or CDI-associated complications including intensive care unit transfer, extended length of stay, 30-day mortality, and toxic megacolon.

Conclusions: Computerized clinical decision support tools can improve diagnostic test stewardship without causing harm. Additional studies are needed to identify key elements of CCDS tools to further optimize testing and assess their effect on adverse clinical outcomes.
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http://dx.doi.org/10.1093/ofid/ofaa366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566360PMC
October 2020

Randomized Control Trial on the Effectiveness of Collagen Cross-linking on Bullous Keratopathy.

Cornea 2020 Nov;39(11):1341-1347

Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong; and.

Purpose: To investigate the long-term effect and safety of collagen cross-linking (CXL) on patients with bullous keratopathy (BK) in a randomized control manner. It is, to our knowledge, the first randomized control study on the effect of CXL on BK.

Methods: Subjects were randomized to receive CXL as in the standard protocol for treating keratoconus or a placebo treatment. Subjects were assessed at baseline and up to 12 months after treatment. Primary outcomes were central corneal thickness (CCT) and pain scores.

Results: Forty-two patients with BK participated in the study treatment, 26 subjects were randomized to the CXL group and 16 subjects to the control group. The reduction of CCT in the CXL group was 37.6 and 63.8 μm at 2 and 4 weeks, respectively, which were significantly higher than that in the control group. However, there was no statistical difference in CCT reduction between the 2 groups at 12 weeks and after. There were no consistent advantages in pain score, corneal clarity, and visual acuity over the controls throughout the 1-year follow-up. However, CXL was associated with more recurrent epithelial defect (12%), and 2 of the 3 subjects with epithelial defect required amniotic membrane transplant.

Conclusions: CXL reduced corneal thickness in the patients with BK, at least for the initial period. However, there were no improvement in pain, corneal clarity, and vision that were of more clinical relevance to the patients. Its short-term benefit was unlikely to outweigh its potential risk of recurrent epithelial defect.
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http://dx.doi.org/10.1097/ICO.0000000000002395DOI Listing
November 2020

Determinants of post-mydriatic intraocular pressure in phakic eyes with prevalent angle closure diseases.

Graefes Arch Clin Exp Ophthalmol 2021 Jan 30;259(1):137-143. Epub 2020 Sep 30.

Department of Ophthalmology, Taipei Veterans General Hospital, 201, Sec. 2, Shih-Pai Rd., Taipei, 11217, Taiwan.

Purpose: This study aimed to identify acute angle closure (AAC) risk following pharmacologic mydriasis and the factors affecting post-mydriatic intraocular pressure (IOP) in a population with a high prevalence of angle closure disease.

Methods: In total, 460 individuals aged ≥ 72 years were enrolled in this cross-sectional community-based screening program. IOP was measured at baseline and 1 hour after mydriasis. Individuals with post-mydriatic IOP spike > 6 mmHg received indentation gonioscopy and IOP-lowering medication. Linear regression analysis was used to identify ocular parameters associated with post-mydriatic IOP elevation.

Results: The mean age of participants was 77.8 ± 4.1 years, and 65.4% of them were men. In total, 21 eyes of 16 participants (3.48%) had post-mydriatic IOP spikes (range: 6-13.7 mmHg); among them, 15 eyes had an IOP of > 21 mmHg. None of the participants developed AAC. All eyes with IOP spikes were phakic, except for one with pseudophakic angle closure. Analysis of 381 participants with at least one phakic eye revealed that higher post-mydriatic IOP and IOP changes were associated with narrower angle grading, more extensive peripheral anterior synechiae, shallower central anterior chamber, and thicker lens. According to multiple linear regression analysis, post-mydriatic IOP was independently associated with baseline IOP and factors suggestive of crowded anterior chamber based on gonioscopic findings and central or peripheral anterior chamber depth evaluation in conjunction with lens thickness.

Conclusion: Post-mydriatic IOP should be measured in phakic eyes with a crowded anterior chamber. Post-mydriatic IOP spikes can be effectively blunted with intervention to prevent AAC.
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http://dx.doi.org/10.1007/s00417-020-04941-zDOI Listing
January 2021

Blood and marrow transplantation during the emerging COVID-19 pandemic: the Seattle approach.

Bone Marrow Transplant 2021 02 26;56(2):305-313. Epub 2020 Sep 26.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

On January 20, 2020, the first patient with coronavirus disease 2019 (COVID-19) in the United States of America was diagnosed in Washington state, which subsequently experienced rapidly increasing numbers of COVID-19 cases, hospitalizations, and deaths. This placed the Seattle Blood and Marrow Transplant Program at Fred Hutchinson Cancer Research Center (Fred Hutch) in the national epicenter of this pandemic. Here, we summarize the experience gained during our rapid response to the COVID-19 pandemic. Our efforts were aimed at safely performing urgent and potentially life-saving stem cell transplants in the setting of pandemic-related stresses on healthcare resources and shelter-in-place public health measures. We describe the unique circumstances and challenges encountered, the current state of the program amidst evolving COVID-19 cases in our community, and the guiding principles for recovery. We also estimate the collateral impact of directing clinical resources toward COVID-19-related care on cancer patients in need of stem cell transplantation. Although our experience was influenced by specific regional and institutional factors, it may help inform how transplant programs respond to COVID-19 and future pandemics.
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http://dx.doi.org/10.1038/s41409-020-01068-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519858PMC
February 2021