bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining Side Effect Variability of Antipsychotic Treatment in Schizophrenia Spectrum Disorders: A Meta-analysis of Variance
Authors: Neumeier Maria S , Homan Stephanie , Vetter Stefan , Seifritz Erich , Kane John M , Huhn Maximilian , Leucht Stefan , Homan Philipp
Published: June 2021

Side effects of antipsychotic drugs play a key role in nonadherence of treatment in schizophrenia spectrum disorders (SSD). While clinical observations suggest that side effect variability between patients may be considerable, statistical evidence is required to confirm this. Here, we hypothesized to find larger side effect variability under treatment compared with control. We included double-blind, placebo-controlled, randomized controlled trials (RCTs) of adults with a diagnosis of SSD treated with 1 out of 14 antipsychotics. Standard deviations of the pre-post treatment differences of weight gain, prolactin levels, and corrected QT (QTc) times were extracted. The outcome measure was the variability ratio of treatment to control for individual antipsychotic drugs and the overall variability ratio of treatment to control across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. We included N = 16 578 patients for weight gain, N = 16 633 patients for prolactin levels, and N = 10 384 patients for QTc time. Variability ratios (VR) were significantly increased for weight gain (VR = 1.08; 95% CI: 1.02–1.14; P = .004) and prolactin levels (VR = 1.38; 95% CI: 1.17–1.62; P < .001) but did not reach significance for QTc time (VR = 1.05; 95% CI: 0.98–1.12; P = 0.135). We found marked differences between individual antipsychotics and increased variability in side effects in patients under treatment with antipsychotics suggesting that subgroups of patients or individual patients may benefit from treatment allocation through stratified or personalized medicine.
Inflammatory Response, Reactive Oxygen Species Production and DNA Damage in Mice After Intrapleural Exposure to Carbon Nanotubes
Authors: Wils Regitze Sølling , Jacobsen Nicklas Raun , Vogel Ulla , Roursgaard Martin , Møller Peter
Published: June 2021

Carbon nanotubes (CNTs) are speculated to cause mesothelioma by persistent inflammation, oxidative stress, tissue injury, and genotoxicity. To investigate the pleural response to CNTs, we exposed C57BL/6 mice by intrapleural injection of 0.2 or 5 µg multiwalled CNTs (MWCNT-7, NM-401, and NM-403) or single-walled CNTs (NM-411). Inflammatory response, cellular reactive oxygen species (ROS) production of pleural lavage cells, and genotoxicity in cells from the mesothelial surface were assessed at days 1 and 90 after the exposure. Long and rigid types of MWCNTs (MWCNT-7 and NM-401) caused acute inflammation, characterized by influx of macrophages, neutrophils, and eosinophils into the pleural cavity. The inflammation was still evident at 90 days after the exposure, although it had reduced dramatically. The cellular ROS production was increased at day 90 after the exposure to MWCNT-7 and NM-401. The short and tangled type of MWCNT (ie NM-403) did not cause pleural inflammation or ROS production in pleural fluid cells. The exposure to NM-411 did not cause consistent inflammation responses or cellular ROS production. Levels of DNA strand breaks and DNA oxidation damage were unaltered, except for NM-411-exposed mice that had increased levels of DNA strand breaks at 90 days after the exposure. In conclusion, the long and rigid CNTs caused prolonged inflammatory response and increased ROS production in pleural lavage cells, yet it was not reflected in higher levels of DNA damage in pleural tissue.
Genomic epidemiology of SARS-CoV-2 transmission lineages in Ecuador
Authors: Gutierrez Bernardo , Márquez Sully , Prado-Vivar Belén , Becerra-Wong Mónica , Guadalupe Juan José , Candido Darlan Da Silva , Fernandez-Cadena Juan Carlos , Morey-Leon Gabriel , Armas-Gonzalez Rubén , Andrade-Molina Derly Madeleiny , Bruno Alfredo , De Mora Domenica , Olmedo Maritza , Portugal Denisse , Gonzalez Manuel , Orlando Alberto , Drexler Jan Felix , Moreira-Soto Andres , Sander Anna-Lena , Brünink Sebastian , Kühne Arne , Patiño Leandro , Carrazco-Montalvo Andrés , Mestanza Orson , Zurita Jeannete , Sevillano Gabriela , Du Plessis Louis , McCrone John T , Coloma Josefina , Trueba Gabriel , Barragán Verónica , Rojas-Silva Patricio , Grunauer Michelle , Kraemer Moritz U G , Faria Nuno R , Escalera-Zamudio Marina , Pybus Oliver G , Cárdenas Paúl
Published: June 2021

Characterisation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic diversity through space and time can reveal trends in virus importation and domestic circulation and permit the exploration of questions regarding the early transmission dynamics. Here, we present a detailed description of SARS-CoV-2 genomic epidemiology in Ecuador, one of the hardest hit countries during the early stages of the coronavirus-19 pandemic. We generated and analysed 160 whole genome sequences sampled from all provinces of Ecuador in 2020. Molecular clock and phylogeographic analysis of these sequences in the context of global SARS-CoV-2 diversity enable us to identify and characterise individual transmission lineages within Ecuador, explore their spatiotemporal distributions, and consider their introduction and domestic circulation. Our results reveal a pattern of multiple international importations across the country, with apparent differences between key provinces. Transmission lineages were mostly introduced before the implementation of non-pharmaceutical interventions, with differential degrees of persistence and national dissemination.
II Old English
Authors: Burns Rachel , Curran Colleen , Yang Kaifan , Kehoe Niamh , Knowles Emma , Pascual Rafael J , Ponirakis Eleni , Tedford Margaret
Published: June 2021

This chapter has eleven sections: 1. Bibliography; 2. Manuscript Studies, Palaeography, and Facsimiles; 3. Cultural and Intellectual Contexts; 4. Literature: General; 5. The Poems of the Exeter Book; 6. The Poems of the Vercelli Book; 7. The Poems of the Junius Manuscript; 8. Beowulf and the Beowulf Manuscript; 9. Other Poems; 10. Prose; 11. Reception. Sections 1, 9, and 11 are by Eleni Ponirakis; section 2 is by Rachel Burns and Colleen Curran; sections 3, 4, and 10 are by Margaret Tedford; section 5 is by Niamh Kehoe; section 6 is by Rafael J. Pascual; section 7 is by Emma Knowles; section 8 is by Rachel Burns and Kaifan Yang.
Subsequent Pressure Injury Development in Mechanically Ventilated Critical Care Patients with Hospital-Acquired Pressure Injury: A Retrospective Cohort Study
Authors: Alderden Jenny , Cadavero Allen , Zhao Yunchuan “Lucy” , Dougherty Desiree , Jung Se-Hee , Yap Tracey L.
Published: June 2021

OBJECTIVE

To identify factors associated with subsequent hospital-acquired pressure injury (HAPrI) formation among patients in surgical and cardiovascular surgical ICUs with an initial HAPrI.

METHODS

Patients admitted to a level 1 trauma center and academic medical center in the Western US between 2014 and 2018 were eligible for this retrospective cohort study. Inclusion criteria were development of an HAPrI stage 2 or above, age older than 18 years, the use of mechanical ventilation for at least 24 hours, and documentation of a risk-based HAPrI-prevention plan including repositioning at least every 2 hours. The primary outcome measure was development of a second, subsequent HAPrI stage 2 or higher. Potential predictor variables included demographic factors, shock, Charleston comorbidity score, blood gas and laboratory values, surgical factors, vasopressor infusions, levels of sedation or agitation, Braden Scale scores, and nursing skin assessment data.

RESULTS

The final sample consisted of 226 patients. Among those, 77 (34%) developed a second HAPrI. Independent risk factors for subsequent HAPrI formation were decreased hemoglobin (odds ratio, 0.71; 95% confidence interval [CI], 0.53–0.92; P < .000), vasopressin infusion (odds ratio, 2.20; 95% CI, 1.17–4.26; P = .02), and longer length of stay in the ICU (odds ratio, 1.01; 95% CI, 1.00–1.02; P = .009).

CONCLUSIONS

Patients with an HAPrI are at high risk of subsequent HAPrI development. Anemia, vasopressin infusion, and longer ICU stays are independent risk factors for repeat HAPrI formation.
Recent Trends in Faculty Promotion in U.S. Medical Schools: Implications for Recruitment, Retention, and Diversity and Inclusion
Authors: Xierali Imam M. , Nivet Marc A. , Syed Zubair A. , Shakil Amer , Schneider F. David
Published: June 2021

Purpose

Faculty promotion is important for retention and has implications for diversity. This study provides an update on recent trends in faculty promotion in U.S. medical schools.

Method

Using data from the Association of American Medical Colleges Faculty Roster, the authors examined trends in faculty promotion over 10 years. Promotion status for full-time assistant and full-time associate professors who started between 2000 and 2009 inclusive was followed from January 1, 2010 to January 1, 2019. The authors used bivariate analyses to assess associations and promotion rates by sex, race/ethnicity, department, tenure status, and degree type.

Results

The promotion rate for assistant professors was 44.3% (2,330/5,263) in basic science departments, 37.1% (17,232/46,473) in clinical science departments, and 33.6% (131/390) in other departments. Among clinical departments, family medicine had the lowest rate of promoting assistant professors (24.4%; 484/1,982) and otolaryngology the highest rate (51.2%; 282/551). Faculty members who were male (38.9%; 11,687/30,017), White (40.0%; 12,635/31,596), tenured (58.7%; 98/167) or tenure-eligible (55.6%; 6,653/11,976), and holding MDs/PhDs (48.7%; 1,968/4,038) had higher promotion rates than, respectively, faculty who were female (36.3%; 7,975/21,998), minorities underrepresented in medicine (URM; 31.0%; 1,716/5,539), nontenured (32.5%; 12,174/37,433), and holding other/unknown degrees (20.6%; 195/948; all P < .001). These differences were less pronounced among associate professors; however, URM and nontenured faculty continued to have lower promotion rates compared with White, Asian, or tenured faculty at the associate professor level.

Conclusions

Promotion rates varied not only by faculty rank but also by faculty sex, race/ethnicity, department, tenure status, and degree type. The differences were more pronounced for assistant professors than associate professors. URM faculty members, particularly assistant professors, were promoted at lower rates than their White and Asian peers. More research to understand the drivers of disparities in faculty promotion seems warranted.
A Question of Scale? Generalizability of the Ottawa and Chen Scales to Render Entrustment Decisions for the Core EPAs in the Workplace
Authors: Ryan Michael S. , Khamishon Rebecca , Richards Alicia , Perera Robert , Garber Adam , Santen Sally A.
Published: June 2021

Purpose

Assessments of the Core Entrustable Professional Activities (Core EPAs) are based on observations of supervisors throughout a medical student’s progression toward entrustment. The purpose of this study was to compare generalizability of scores from 2 entrustment scales: the Ottawa Surgical Competency Operating Room Evaluation (Ottawa) scale and an undergraduate medical education supervisory scale proposed by Chen and colleagues (Chen). A secondary aim was to determine the impact of frequent assessors on generalizability of the data.

Method

For academic year 2019–2020, the Virginia Commonwealth University School of Medicine modified a previously described workplace-based assessment (WBA) system developed to provide feedback for the Core EPAs across clerkships. The WBA scored students’ performance using both Ottawa and Chen scales. Generalizability (G) and decision (D) studies were performed using an unbalanced random-effects model to determine the reliability of each scale. Secondary G- and D-studies explored whether faculty who rated more than 5 students demonstrated better reliability. The Phi-coefficient was used to estimate reliability; a cutoff of at least 0.70 was used to conduct D-studies.

Results

Using the Ottawa scale, variability attributable to the student ranged from 0.8% to 6.5%. For the Chen scale, student variability ranged from 1.8% to 7.1%. This indicates the majority of variation was due to the rater (42.8%–61.3%) and other unexplained factors. Between 28 and 127 assessments were required to obtain a Phi-coefficient of 0.70. For 2 EPAs, using faculty who frequently assessed the EPA improved generalizability, requiring only 5 and 13 assessments for the Chen scale.

Conclusions

Both scales performed poorly in terms of learner-attributed variance, with some improvement in 2 EPAs when considering only frequent assessors using the Chen scale. Based on these findings in conjunction with prior evidence, the authors provide a root cause analysis highlighting challenges with WBAs for Core EPAs.
The Gait Outcomes Assessment List for Children With Lower Limb Difference (GOAL-LD): Assessment of Reliability and Validity
Authors: Griffiths Alison L. , Donnan Leo T. , Iobst Christopher A. , Kelley Simon P. , Bouchard Maryse , Narayanan Unni G.
Published: June 2021

Background:

The Gait Outcomes Assessment List for children with Lower Limb Difference (GOAL-LD) is a patient and parent-reported outcome measure that incorporates the framework of the International Classification of Functioning, Disability, and Health. This prospective multicenter cohort study evaluates the validity and reliability of the GOAL-LD and the differences between parent and adolescent report.

Method:

One hundred thirty-seven pediatric patients aged over 5 years attending limb reconstruction clinics at the participating sites were assessed at baseline, and a self-selected cohort also completed an assessment 2 to 6 weeks later. Construct and criterion validity were assessed by comparing GOAL-LD scores with a measure of limb deformity complexity (LLRS-AIM) and the Pediatric Outcomes Data Collection Instrument, using Spearman correlation coefficients. Face and content validity were determined through ratings of item importance. Test-retest reliability was reported as an intraclass correlation coefficient and internal consistency using Cronbach α. Adolescent reports were compared with their parents using paired t tests.

Results:

The GOAL-LD demonstrated a moderate negative correlation with the LLRS-AIM (r=−0.40, P<0.001) and was able to discriminate between deformity complexity groups as defined by the LLRS-AIM (χ2=11.43, P=0.022). Internal consistency was high across all domains (α≥0.68 to 0.97). Like domains of the Pediatric Outcomes Data Collection Instrument and the GOAL-LD were well correlated. Parents reported a lower total GOAL-LD score when compared with adolescents (mean difference 3.04; SE 1.06; 95% confidence interval, 0.92-5.16; P<0.01); however this difference was only significant for body image and self-esteem (Domain F) and gait appearance (Domain D). Test-retest reliability remained high over the study period (intraclass correlation coefficient 0.85; SE 0.03; 95% confidence interval, 0.77-0.91).

Conclusions:

The GOAL-LD is a valid and reliable self and parent-reported outcome measure for children with lower limb difference. Parents report a lower level of function and attribute a higher importance to items when compared with their children. The GOAL-LD helps to communicate parent and child perspectives on their function and priorities and therefore has the capacity to facilitate family centered treatment planning and care.

Level of Evidence:

Level II—diagnostic. Prospective cross-sectional and a longitudinal cohort design.
Pretreatment Eosinophil Counts in Patients With Advanced or Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1 Checkpoint Inhibitors
Authors: Mota Jose Mauricio , Teo Min Yuen , Whiting Karissa , Li Han A. , Regazzi Ashely M. , Lee Chung-Han , Funt Samuel A. , Bajorin Dean , Ostrovnaya Irina , Iyer Gopa , Rosenberg Jonathan E.
Published: June 2021

Eosinophils influence antitumor immunity and may predict response to treatment with immune checkpoint inhibitors (ICIs). To examine the association between blood eosinophil counts and outcomes in patients with advanced or metastatic urothelial carcinoma (mUC) treated with ICIs, we identified 2 ICI-treated cohorts: discovery (n=60) and validation (n=111). Chemotherapy cohorts were used as comparators (first-line platinum-based chemotherapy, n=75; second-line or more pemetrexed, n=77). The primary endpoint was overall survival (OS). Secondary endpoints were time on treatment (ToT) and progression-free survival. Univariate and multivariate analyses were performed using Cox proportional hazard models. Associations between changes in eosinophil count at weeks 2/3 and 6 after the start of ICI treatment were analyzed using landmark analyses. Baseline characteristics of the ICI cohorts were similar. In the discovery cohort, an optimal cutoff for pretreatment eosinophil count was determined [Eos-Lo: <100 cells/µL; n=9 (15%); Eos-Hi: ≥100 cells/µL; n=51 (85%)]. Eos-Lo was associated with inferior outcomes [OS: hazard ratio (HR), 3.98; 95% confidence interval (CI), 1.85–8.56; P<0.013; ToT: HR, 2.45; 95% CI, 1.17–5.10; P=0.017]. This was confirmed in the validation cohort [Eos-Lo: n=17 (15%); Eos-Hi: n=94 (85%)] (OS: HR, 2.51; 95% CI, 1.31–4.80; P=0.006; ToT: HR, 2.22; 95% CI, 1.2–3.80; P=0.004), and remained significant after adjustment for other prognostic factors. Changes in eosinophil counts at weeks 2/3 and 6 were not clearly associated with outcomes. In chemotherapy cohorts, eosinophil counts were not associated with outcomes. In conclusion, low pretreatment eosinophil count was associated with poorer outcomes in patients with mUC treated with ICIs, and may represent a new predictive biomarker.
Irritable bowel syndrome in China: a review on the epidemiology, diagnosis, and management
Authors: Liu Yi-Lin , Liu Jin-Song
Published: June 2021

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease worldwide. Current guidelines of IBS are mostly based on the western populations and expected to vary in different communities. China has a large population and a vast literature is available on IBS. Due to linguistic variations in the literature, the studies are not widely known and their conclusions thus remain largely obscured to the western medical literature. In this article, we reviewed the published literatures on the investigations of IBS epidemiology, diagnosis, and management in the Chinese population and emphasized the different findings gleaned from the western publications. The detailed literature review will benefit understanding of and promote future study on IBS.
Anti-aversive effect of 2-arachidonoylglycerol in the dorsolateral periaqueductal gray of male rats in contextual fear conditioning and Vogel tests
Authors: Brianis Rayssa C. , Lima Rita C. , Moreira Fabrício A. , Aguiar Daniele C.
Published: June 2021

The endocannabinoid system modulates the stress coping strategies in the dorsolateral periaqueductal grey (dlPAG). The most relevant endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG) exert inhibitory control over defensive reactions mediated by the dlPAG. However, the protective role of anandamide is limited by its lack of effect in higher concentrations. Thus, the 2-AG emerges as a complementary target for developing new anxiolytic compounds. Nevertheless, the role of 2-AG on stress responsivity may vary according to the nature of the stimulus. In this study, we verified whether the dlPAG injection of 2-AG or inhibitors of its hydrolysis induce anxiolytic-like effects in male Wistar rats exposed to behavioral models in which physical stress (mild electric shock) is a critical component, namely the contextual fear conditioning test (CFC) and the Vogel conflict test (VCT). We also investigated the contribution of cannabinoid receptor type 1 (CB1) and type 2 (CB2) in such effects. The facilitation of 2-AG signaling in the dlPAG reduced contextual fear expression and exhibited an anxiolytic-like effect in the VCT in a mechanism dependent on activation of CB1 and CB2. However, the VCT required a higher dose than CFC. Further, the monoacylglycerol inhibitors, which inhibit the hydrolysis of 2-AG, were effective only in the CFC. In conclusion, we confirmed the anti-aversive properties of 2-AG in the dlPAG through CB1 and CB2 mechanisms. However, these effects could vary according to the type of stressor and the anxiety model employed.
Mobile health application usage and quality of care at a hypertension clinic: an observational cohort study
Authors: Agnihothri Saligrama , Cui Leon , Rajan Balaraman , Banerjee Anu , Ramanujan Ramanujapuram
Published: June 2021

Objective:

The aim of this study was to test whether a physician-supervised web-based app, integrated with an electronic medical record, helps in improving blood pressure (BP) management in clinical practice.

Materials and Methods:

An observational study of 1633 patients seen at a hypertension clinic managed by an endocrinologist with two cohorts (726 adopted the app and 907 had not). The app allowed patients and doctors to monitor BP, blood sugar and other vital signs. Patients decided whether to opt in to using the app and how often to upload their readings. The provider could offer feedback and communicate with patients through the app. We evaluated the change in office-based BP measurement before and after app adoption (at least 12 months apart). We performed a difference-in-difference analysis along with matching based on patient-individual characteristics.

Results:

The difference-in-difference estimates were 6.23 mmHg systolic [95% confidence interval (95% CI) 0.87–11.59] for patients with SBP 150 mmHg or above, 4.01 mmHg systolic (95% CI 1.11–6.91) for patients with SBP 140 mmHg or above, 4.37 mmHg diastolic (95% CI 1.06–7.68) for patients with DBP 90 mmHg or above, 1.89 mmHg systolic (95% CI 0.58–3.2) and 0.87 mmHg diastolic (95% CI 0.17–1.57) overall for an average patient. Higher frequency of app usage was also associated with a greater reduction in BP.

Conclusion:

Use of an mHealth app in a clinical practice, was associated with a significant reduction in BP for average patients as well as high-severity patients. Physician-supervised mHealth apps in a clinical practice could be instrumental in managing patient BP.
PSEUDOPANUVEITIS AS A HARBINGER FOR SYSTEMIC LEUKEMIA RECURRENCE
Authors: Altman Marcus T. , Staubach Zane , Dunlap Jennifer , Zaki Amr , Skalet Alison H. , Leonard Jessica , Lin Phoebe
Published: June 2021

Purpose:

To describe a patient with a history of pre–B-cell acute lymphoblastic leukemia in remission, who developed recurrent alternating intraocular leukemia manifesting with pseudohypopyon, uveal mass, and serous retinal detachment. In multiple instances, this constellation of ocular findings preceded systemic leukemia recurrence.

Method:

Case report.

Results:

A 29-year-old man with a history of pre–B-cell acute lymphoblastic leukemia, in remission after a hematopoietic stem cell transplant, presented with pseudohypopyon, uveal lesions, and serous retinal detachment of the right eye. Comprehensive workup for infectious and inflammatory etiologies was unremarkable, and a bone marrow biopsy revealed systemic recurrence of leukemia. One year later, while again in remission, the patient developed a pseudohypopyon, uveal mass, and serous retinal detachment of the other eye. Repeat bone marrow biopsy showed impending leukemia relapse, which occurred 1 month later. Orbital radiation resulted in complete ocular resolution.

Conclusion:

The constellation of pseudohypopyon, serous retinal detachment, and uveal mass (pseudopanuveitis) should be recognized as a harbinger for systemic pre-B ALL recurrence.
Corneal Toxicity of Intravitreal Methotrexate Used for the Treatment of Proliferative Vitreoretinopathy in Silicone Oil-Filled Eyes: A Case Series
Authors: Shen-Sampas John H. , Ahmad Tessnim R. , Stewart Jay M.
Published: June 2021

Purpose:

The purpose of this study was to evaluate the corneal toxicity of intravitreal methotrexate used for the prevention of proliferative vitreoretinopathy (PVR).

Methods:

In this retrospective case series, eyes with recurrent retinal detachment secondary to PVR were treated with intravitreal injections of 400 μg methotrexate at an average frequency of every 7 days after vitrectomy with silicone oil tamponade. Corneas were examined for corneal epitheliopathy by slit-lamp biomicroscopy before each injection.

Results:

Thirteen eyes of 12 patients were reviewed. All had a history of recurrent retinal detachment secondary to PVR treated with vitrectomy and silicone oil. The median age was 35 years (range: 9–83). Four patients (33%) were female. The median follow-up duration was 8 weeks (range: 5–10). The median BCVA (logMAR notation) was 2.00 preoperatively, 2.00 at 1 month postoperatively, and 2.00 at the most recent follow-up (P = 0.969). Ten eyes (77%) were pseudophakic. Nine eyes (69%) had a preexisting ocular comorbidity. The median number of injections was 8 (range: 5–10). The median interval time between each injection was 7.0 days (range: 5.8–10.5), and the median follow-up period beyond last injection was 16 weeks (range: 8–28). Two eyes (15.4%) developed mild corneal epitheliopathy during the course of the treatment.

Conclusions:

Most eyes in this small series tolerated methotrexate injections without corneal toxicity. In eyes that developed epitheliopathy, the findings were mild and not treatment-limiting.
Corneal Effects of Tea Tree Oil
Authors: Tharmarajah Brindhan , Coroneo Minas Theodore
Published: June 2021

Purpose:

The purpose of this study is to report a case of corneal epithelial defects resulting from topical treatment of blepharitis with tea tree oil (TTO).

Methods:

A 44-year-old man with a 1 year history of blepharitis non-responsive to eyelid hygiene was found to have signs of Demodex infestation. He was treated with a topical, off-label 50% TTO solution. Shortly afterward, the patient complained of bilateral ocular discomfort.

Results:

Slit-lamp examination revealed conjunctival injection and a corneal epithelial defect in both eyes. Treatment with lubricant, antibiotic, and steroid eye drops as well as bandage contact lenses was required to facilitate corneal healing.

Conclusions:

Topical use of off-label, 50% concentration TTO can result in corneal epithelial defects. Eye care professionals should remain aware of this risk and only use approved, low-concentration TTO products when treating Demodex-related blepharitis.
Impact of Early Intraocular Pressure Elevation on Postoperative Outcomes After Descemet Membrane Endothelial Keratoplasty in Non-glaucoma Patients
Authors: Lentzsch Anna M. , Adler Werner , Siebelmann Sebastian , Grajewski Rafael , Schrittenlocher Silvia , Bachmann Bjoern O. , Cursiefen Claus , Heindl Ludwig M. , Matthaei Mario
Published: June 2021

Purpose:

The purpose of this study was to investigate the impact of transient elevations in postoperative intraocular pressure (IOP) on the clinical outcome of Descemet membrane endothelial keratoplasty (DMEK) surgery in non-glaucoma patients.

Methods:

Retrospective analysis from a prospective database of eyes without preexisting glaucoma that underwent DMEK with 90% anterior chamber and 20% sulfur hexafluoride endotamponade. Group A included eyes without postoperative IOP increase (IOP <30 mm Hg and a relative increase from preoperative value <10 mm Hg). Group B included eyes with IOP elevation (postoperative IOP ≥30 mm Hg or a relative increase from preoperative value ≥10 mm Hg) handled according to a standardized protocol. The impact of elevated IOP within 3 days after DMEK surgery was evaluated regarding best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell count (ECC) at 1, 3, and 6 months.

Results:

One hundred seventy-six eyes from 164 patients were included. An IOP increase after DMEK occurred in 20 eyes (11.3%; 19 patients, group B), and the mean peak IOP was 48 ± 12 mm Hg (range 32–69 mm Hg). There were no significant postoperative differences in BCVA, CCT, and ECC on comparing both groups. The BCVA increased significantly (P < 0.001, respectively), whereas CCT (P < 0.001, respectively) and ECC (P < 0.001, respectively) decreased significantly from preoperative values. The rebubbling rate tended to be higher in group B without statistical significance (6.4% vs. 10%, P = 0.648).

Conclusions:

Temporary IOP elevation after DMEK may not affect functional and morphological outcomes in non-glaucoma patients. However, careful postoperative IOP monitoring and appropriate management are crucial to avoid irreversible ocular damage.
Endothelial cell loss after accelerated corneal crosslinking using pachymetry-guided hypo-osmolar riboflavin dosing in thin keratoconic corneas
Authors: Yurttaser Ocak Serap , Mangan Mehmet Serhat
Published: June 2021

Purpose:

To report the intraoperative changes in corneal pachymetry, as well as the efficacy and safety of accelerated corneal crosslinking (A-CXL) treatment using only hypo-osmolar riboflavin (HO-RF) solution in progressive keratoconus patients with thin corneas.

Setting:

University of Health Sciences, Prof. Dr. Cemil Tascioglu Education and Research Hospital, Istanbul, Turkey

Design:

Retrospective study.

Methods:

Thin keratoconic corneas (<400 m without epithelium) who had A-CXL (9 mW/cm2-10 minutes) with HO-RF solution application were enrolled in the study. Intraoperative corneal pachymetric changes and uncorrected and corrected distance visual acuities (UDVA and CDVA), refraction power values, topographic values, and endothelial cell density (ECD) measurements were recorded preoperatively and at 1st, 3rd, 6th, and 12th month follow-up postoperatively.

Results:

31 eyes of 25 patients (mean age: 24.17 ± 3.07 years) included in this study. The mean thickness increased to 438 μm (P = .001) after the application of HO-RF solution, and it was reduced to 424 μm (P = .001) after ultraviolet irradiation. At all postoperative visits after month 1, there was a significant increase in both UDVA (P < .05) and CDVA (P < .01) values and a significant decrease in both maximum keratometry (P < .05) and ECD (P < .01) values.

Conclusions:

Accelerated CXL with only HO-RF solution application throughout the procedure in thin corneas was effective but seemed to result in a significant ECD decrease postoperatively.
Repeated Annual Health Risk Assessments With Intervention Did Not Reduce 10-year Cardiovascular Disease Risk
Authors: Hene Nceba , Wood Paola , Schwellnus Martin , Jordaan Esme , Laubscher Ria
Published: June 2021

Objective:

To determine if repeat annual health risk assessments (RAHRAs) with intervention reduce 10-year cardiovascular disease (CVD) risk in financial sector employees.

Methods:

Retrospective analysis from RAHRAs in 13,737 employees over 4 years. We report changes in 10-year FRS for CVD (%) and risk factors after 1 (GR1), 2 (GR2), and 3 (GR 3) RAHRAs.

Results:

Mean FRS increased with RAHRAs (GR1: +0.4%; GR2: +0.7%; GR3: +0.8%) (P < 0.001) and was higher for GR3 versus GR1 (P < 0.001) and GR2 (pairwise: P < 0.0355). RAHRAs were associated with increased inadequate fruit/vegetable intake (GR1: +5.4%; GR2: +9.8%; GR3: +15.8%) (all pairwise: P < 0.001) and overweight (GR1: +5.4% vs GR2: +9.8%) (P < 0.001) and only hypercholesterolemia decreased (GR1: −4.4% vs GR3: −9.6%) (P < 0.001).

Conclusion:

RAHRAs did not reduce 10-year CVD risk in financial sector employees. Role of RAHRAs in chronic disease management requires further study.
Evaluation of prognostic value of neutrophil-to-lymphocyte ratio in patients with acute-on-chronic liver failure or severe liver injury from chronic HBV infection
Authors: Sun Jian , Guo Hongying , Yu Xueping , Chen Jingwen , Zhu Haoxiang , Qi Xun , Zhang Xueyun , Han Jiajia , Liu Xiaoqin , Yang Jianghua , Wang Jiefei , Qian Zhiping , Huang Yuxian , Mao Richeng , Zhang Jiming
Published: June 2021

Background and aims

Acute-on-chronic liver failure (ACLF) is associated with bacterial infection and poor outcome. Neutrophil-to-lymphocyte ratio (NLR) is used to assess bacterial infection and immune dysfunction in numerous diseases. We aimed to evaluate NLR as a prognostic biomarker and to explore its combination with accepted prognostic models in ACLF patients.

Methods

This retrospective study included patients with ACLF or severe liver injury from chronic HBV infection admitted to three tertiary academic hospitals in China from 2013 to 2019. Baseline NLR was correlated with ACLF grade, bacterial infection, survival and accepted ACLF scores.

Results

Baseline NLR values were significantly increased in nonsurvivors and patients with bacterial infection at or after admission and were unaffected by cirrhotic status in 412 transplant-free patients included in three cohorts. Compared with accepted scores, NLR showed moderate accuracy in predicting 28-day mortality and high accuracy in predicting 90-day mortality. Three levels of mortality risk were graded on the basis of NLR values (<3.10, 3.10–4.79 and >4.79), and NLR >4.79 was associated with 53.2–60.0% 28-day and 75.0–80.0% 90-day mortality in these cohorts. Multivariate analyses indicated that NLR retained statistical significance independently of CLIF consortium organ failure score (CLIF-C OFs). NLR-based CLIF-C ACLF score was primarily developed and showed excellent performance in predicting 28/90-day mortality.

Conclusions

NLR is a dependable biomarker for bacterial infection assessment and short-term mortality prediction in ACLF patients and can be used jointly with CLIF-C OFs to improve the accuracy of mortality prediction in patients with the disease. NLR-based CLIF-C ACLF model needs further validation.
Simplified 6-month prediction scores for primary biliary cholangitis patients treated with ursodeoxycholic acid
Authors: Pinyopornpanish Kanokwan , Chadalavada Pravallika , Talal Sarmini Muhammad , Khoudari George , Alomari Mohammad , Padbidri Vinay , Romero-Marrero Carlos
Published: June 2021

Objectives

To develop a prognostic score evaluating treatment response at 6 months after ursodeoxycholic acid (UDCA) initiation in primary biliary cholangitis (PBC) patients.

Methods

Adult PBC patients who were newly prescribed UDCA at our institution (n = 292) were included. Significant determinants of liver-related adverse events in the multivariable Cox model were used for score development, weighted by β-coefficients. Discrimination ability was assessed using Harrell’s C-statistic. The performance of our model was compared to the previous models.

Results

Our model included the following variables evaluated at 6 months: (1) alkaline phosphatase decline of less than 50% from baseline and >upper limit normal (ULN) (2 points); (2) bilirubin >ULN (2 points); (3) albumin <lower limit normal (1 point). The score ranged from 0 to 5 points. C-statistic estimates were 0.87 (overall cohort), 0.87 (no cirrhosis) and 0.77 (cirrhosis), indicating good discrimination of treatment response. Patients with scores ≥3 points had significant shorter transplant-free survival (TFS) than scores <3 points (P < 0.001). The TFS rates for patients with score ≥3 points at 5, 10 and 15 years were 52, 26 and 7%, and for patients with scores <3 points were 96, 92 and 82%, respectively. There was no significant difference between the performance of our 6-month model and the previous models (Paris I, Paris II, Barcelona, Rotterdam and GLOBE scores evaluated at 12 months) in predicting liver-related outcomes (all P = NS).

Conclusion

This novel 6-month prognostic model showed good prognostic performance. Utilization of this score would identify patients with suboptimal responses to UDCA earlier.
Mean platelet volume and platelet to lymphocyte count ratio are associated with hepatitis B-related liver fibrosis
Authors: Kosekli Mehmet Ali
Published: June 2021

Aim

Chronic hepatitis B is associated with important morbidity and mortality. Inflammation has a pivotal role in hepatic fibrosis of this population. Hemogram-derived inflammatory predictors, such as mean platelet volume (MPV) and platelet to lymphocyte ratio (PLR), are supposed as inflammatory markers in various diseases. We aimed to compare MPV and PLR of the patients with chronic hepatitis B to those of healthy controls and to observe possible correlation between these markers and fibrosis.

Methods

Chronic hepatitis B patients that visited our outpatient gastroenterology clinics were enrolled in the study. Healthy volunteers were enrolled as controls. MPV, PLR and other parameters of the study groups were compared.

Results

Median MPV of the mild fibrosis, advanced fibrosis control groups were 8.1 (6.6–13) fL, 8.2 (6.3–14.5) fL and 7.2 (4.6–8.9) fL, respectively (P < 0.001). Median PLR of the mild fibrosis, advanced fibrosis control groups were 99.5 (36–259) %, 119 (61–1547) % and 122 (64–197) %, respectively (P = 0.02). PLR was correlated with the ISHAK score (r = 0.32, P = 0.002). A MPV value greater than 7.52 fL have 80% sensitivity and 56% specificity in determining advanced fibrosis (AUC: 0.68, P = 0.002, 95% confidence interval, 0.58–0.77).

Conclusion

We think that increased MPV and decreased PLR are characteristics of chronic hepatitis B disease. Moreover, increased MPV could predict advanced fibrosis in this population.
Prognostic significance of 18F-FDG PET/CT parameters in IDH-1 wild-type GBM and correlation with molecular markers
Authors: Dev Indraja Devidas , Puranik Ameya D. , Purandare Nilendu C. , Gupta Tejpal , Sridhar Epari , Shetty Prakash , Moiyadi Aliasgar , Agrawal Archi , Shah Sneha , Rangarajan Venkatesh
Published: June 2021

Aim

To assess the prognostic role of metabolic parameters on 18F-FDG PET/CT & correlation with molecular markers in IDH-1 wild-type GBM.

Methods

A total of 129 patients with brain lesions showing equivocal findings on baseline MRI who were referred for fluoro-deoxy-glucose PET/CT were analyzed. Of these, 50 underwent surgery/biopsy and postoperative histopathological diagnosis of IDH-1 wild-type GBM. SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG) & T/w ratio was calculated. Median metabolic parameters were used for stratification. Overall survival was calculated using Kaplan–Meier method and was compared using log rank test. P value < 0.05 was considered significant. Multivariate analysis was done using Cox proportional hazard model. Correlation between metabolic parameters and molecular markers was done using Mann–Whitney U test.

Results

Median of SUVmax, T/w ratio, MTV, TLG, 18.3, 2.09, 61, 409. Average overall survival (OS) for T/w ratio >2.08 was 5 months, <2.08 was 18 months (P value 0.001). For MTV >61 was 4 months, <61 was 18 months (P value 0.001). Similarly, for TLG >409 was 5 months while for <409 was 19 months (P value 0.001). SUVmax was not significant for OS. In multivariate analysis, age was the statistically significant independent prognostic factor.

Conclusion

Metabolic parameters of fluoro-deoxy-glucose PET/CT help in prognosticating IDH-1 wild-type GBM. Higher MiB-1 index correlates with higher T/w ratio and is associated with poor overall survival.
The solid organ transplant recipient with SARS-CoV-2 infection
Authors: Laracy Justin C. , Miko Benjamin A. , Pereira Marcus R.
Published: June 2021

Purpose of review

The COVID-19 pandemic is a major challenge to global health, particularly among vulnerable populations. Here, we describe the emerging epidemiology and relevant data on treatment options for COVID-19. We discuss the implications of current knowledge for solid organ transplant (SOT) recipients.

Recent findings

Risk factors and outcomes of COVID-19 among SOT recipients remain uncertain, but recent data suggest similar outcomes to the general population. Case reports of donor-derived SARS-CoV-2 infection are emerging. Few studies on treatment of COVID-19 among SOT recipients are available, and therefore, general recommendations are similar to the general population. Vaccine efficacy in the SOT population is uncertain.

COVID-19 remains a significant threat to SOT recipients and studies on treatment and prevention specific to this population are urgently needed. Although vaccines represent the greatest hope to control this pandemic, their efficacy in this immunocompromised population is uncertain.
Emerging fungal pathogens in solid organ transplantation
Authors: Mishkin Aaron
Published: June 2021

Purpose of review

This review examines recent cases and updated literature on emerging or newly resistant fungal infections in solid organ transplantation.

Recent findings

Candida auris, a newly described candida capable of drug resistance and persistence in the environment, is a growing concern with both published cases on donor-derived transmission and a hospital outbreak involving liver transplant recipients. Infections with non-albicans candida species are also increasing in incidence in SOT recipients, leading to increasing antifungal resistance and higher mortality. Aspergillus usti has emerged in immunocompromised patients on antifungal prophylaxis. Cryptococcus species continue to be responsible for a number of infections in SOT recipients. Dimorphic fungi, endemic to geographic areas and responsible for sporadic infections in SOT recipients are noted to have an expanding geographic area. Emergomyces are newly classified groups of five species of dimorphic fungi noted to disseminated disease in immunocompromised patients including SOT recipients.

Emerging fungal species and the development of resistance in well entrenched fungal pathogens impacts SOT recipients and those caring for them. Knowledge of these trends aids in the successful identification and optimal treatment of these challenging conditions.
In-vitro antifungal susceptibility of the genus Sporothrix and correlation with treatment options for sporotrichosis: a systematic review
Authors: Koehler Alessandra , Pagani Danielle M. , da Silva Hellwig Alessandra H. , Scroferneker Maria L.
Published: June 2021

Sporotrichosis is an infection with global distribution caused by the dimorphic fungi of the genus Sporothrix, whose main pathogenic species include Sporothrix schenckii, Sporothrix brasiliensis, Sporothrix globosa, and Sporothrix luriei. Itraconazole and amphotericin B are the most used antifungals for the treatment. The aim of this review was to compile the in-vitro susceptibility data of Sporothrix spp. found in literature and correlate this data with the treatment guidelines for sporotrichosis. The systematic review was performed according to the Cochrane methodology and with PICOS (Participants, Intervention, Comparators, Outcomes, Study Design) strategy. Thirty-six studies were included that used the filamentous and/or the yeast phases to perform the susceptibility tests. Three studies that evaluated the association of antifungals using the checkerboard method were also included. The data found were, whenever possible, compared with the defined Epidemiological Cutoff Values (ECVs). Analyzing only the minimum inhibitory concentration (MIC) values, the most effective antifungal in vitro was terbinafine. However, this is not the same result as observed in vivo. Both itraconazole and amphotericin B presented in-vitro activity. However, many studies have shown that isolates can acquire resistance mechanisms to these antifungals (MIC > ECV), which deserves attention. Further studies are needed to translate in-vitro susceptibility data into clinical practice, and also to determine ECVs for more antifungals and Sporothrix species.
Urinary Large Cell Neuroendocrine Carcinoma
Authors: Wang Gang , Yuan Ren , Zhou Chen , Guo Charles , Villamil Carlos , Hayes Malcolm , Eigl Bernhard J. , Black Peter
Published: June 2021

Large cell neuroendocrine carcinoma (LCNEC) of the urinary tract is a rare disease. We present a relatively large retrospective cohort of urinary LCNEC, 20 from the urinary bladder, and 2 from the ureter, from a single institution. The patients included 16 men and 6 women with a median age of 74.5 years. Most LCNEC presented at an advanced stage with tumors invading the muscularis propria and beyond (21/22). Eight cases were pure LCNEC, while 14 cases were mixed with other histologic types, including conventional urothelial carcinoma (n=9), carcinoma in situ (n=7), small cell carcinoma (n=6), and urothelial carcinoma with glandular (n=3) features. Most LCNEC expressed neuroendocrine markers synaptophysin (22/22), chromogranin (13/16), CD56 (7/7), TTF1 (8/8), and INSM1 (2/3). They were negative for common urothelial markers including HMWCK (0/3), p40/p63 (0/6), CK20 (0/10), and had variable GATA3 staining (4/8). Ki-67 stained 25% to nearly 100% tumor cell nuclei. Patient survival was associated with cancer stage, and pure LCNEC showed worse survival than mixed LCNEC. Compared with small cell carcinoma at similar stages from a prior study, LCNEC had a worse prognosis only when patients developed metastatic disease. For organ-confined LCNEC, neoadjuvant chemotherapy followed by radical resection is the treatment option to achieve long-term survival.
Intestinal Abnormalities in Patients With SARS-CoV-2 Infection
Authors: Yantiss Rhonda K. , Qin LiHui , He Bing , Crawford Carl V. , Seshan Surya , Patel Sanjay , Wahid Nabeel , Jessurun Jose
Published: June 2021

Approximately 20% of patients with symptomatic syndrome-associated coronavirus-2 (SARS-CoV-2) infection have gastrointestinal bleeding and/or diarrhea. Most are managed without endoscopic evaluation because the risk of practitioner infection outweighs the value of biopsy analysis unless symptoms are life-threatening. As a result, much of what is known about the gastrointestinal manifestations of coronavirus disease-2019 (COVID-19) has been gleaned from surgical and autopsy cases that suffer from extensive ischemic injury and/or poor preservation. There are no detailed reports describing any other gastrointestinal effects of SARS-CoV-2 even though >3,000,000 people have died from COVID-19 worldwide. The purpose of this study is to report the intestinal findings related to SARS-CoV-2 infection by way of a small case series including one with evidence of direct viral cytopathic effect and 2 with secondary injury attributed to viral infection. Infection can be confirmed by immunohistochemical stains directed against SARS-CoV-2 spike protein, in situ hybridization for spike protein-encoding RNA, and ultrastructural visualization of viruses within the epithelium. It induces cytoplasmic blebs and tufted epithelial cells without inflammation and may not cause symptoms. In contrast, SARS-CoV-2 infection can cause gastrointestinal symptoms after the virus is no longer detected, reflecting systemic activation of cytokine and complement cascades rather than direct viral injury. Reversible mucosal ischemia features microvascular injury with hemorrhage, small vessel thrombosis, and platelet-rich thrombi. Systemic cytokine elaboration and dysbiosis likely explain epithelial cell injury that accompanies diarrheal symptoms. These observations are consistent with clinical and in vitro data and contribute to our understanding of the protean manifestations of COVID-19.