bluuebunny/crossref_metadata_2025 huggingface dataset:
EZH2-mediated lncRNA ABHD11-AS1 promoter regulates the progression of ovarian cancer by targeting miR-133a-3p
Authors: Zhang Wen , Huang Xin , Shi Jianguo
Published: January 2021

Long-chain noncoding RNAs (lncRNAs) are involved in a wide range of biological and pathological processes in ovarian cancer. The purpose of this study was to investigate the effects of EZH2-mediated ABHD11-AS1 promoter on the pathogenesis of ovarian cancer. The expression levels of EZH2, ABHD11-AS1 and miR-133a-3p were examined in ovarian cancer tissues using reverse transcription-quantitative PCR. Cell proliferation was evaluated using cell counting kit 8 assay, and cell invasion/migration was determined using a Transwell assay. Cell apoptosis was evaluated using flow cytometry. Dual luciferase assay was performed to confirm the interaction between ABHD11-AS1 and miR-133a-3p. The binding site of H3K27me3 on ABHD11-AS1 promoter was confirmed by ChIP. The expression of ABHD11-AS1 was significantly upregulated in ovarian cancer samples, and its levels were closely associated with lymph node metastasis, tumor stage and 3-year survival rate. Furthermore, interference of ABHD11-AS1 suppressed the proliferation, migration and invasion of ovarian cancer cells, while cell apoptosis was promoted. Additionally, miR-133a-3p could be a novel target of ABHD11-AS1, and EZH2-mediated H3K27me3 protein might bind to ABHD11-AS1 promoter directly. Moreover, rescue experiments indicated that the effects caused by ABHD11-AS1 knockdown on the malignant characteristics of ovarian cancer cells were notably enhanced by miR-133a-3p mimics, whereas the influences on cell growth and metastasis induced by overexpressed ABHD11-AS1 were abrogated by the restoration of miR-133a-3p expression. In summary, EZH2-mediated enrichment of H3K27me3 on ABHD11-AS1 promoter could regulate the progression of ovarian cancer via miR-133a-3p. Therefore, EZH2/ABHD11-AS1/miR-133a-3p axis might be a putative candidate for targeted treatment of ovarian cancer.
A Multicentre Retrospective Analysis of Toxicity in 6-weekly Versus 3-weekly Pembrolizumab
Authors: Rowe Michael , Eastlake Leonie , Norris Timothy , Farley Timothy , Talbot Toby
Published: January 2021

Pembrolizumab is an anti–programmed cell death protein 1 immune checkpoint inhibitor with a dosing schedule of 200 mg 3 weekly (q3w). Dose of 400 mg 6 weekly (q6w) was approved based on simulation of dose/exposure relationships and predicted no difference in toxicity. We present real-world comparative toxicity data. Patients receiving pembrolizumab for any indication between March and December 2019 were included across 3 regional centers. Toxicity data were collected retrospectively using Common Terminology Criteria for Adverse Events, v5.0. Clinically significant immune-related adverse events (CSirAE) were defined as immune-related events and grade ≥3 rash. Data were analyzed using incidence (Poisson distribution) and incidence ratio. Overall, 63 patients started on q6w and 110 patients received q3w. There were 3 (q6w) and 8 (q3w) grade 3–5 CSirAE and 13 (q6w) and 31 (q3w) grade 1–2 CSirAE. The incidence of grade 3–5 CSirAE was 0.77 (95% confidence interval: 0.16–2.24) per 100 patient-months in q6w and 0.68 (95% confidence interval: 0.29–1.34) per 100 patient-months in q3w (incidence ratio of 1.13; 95% confidence interval: 0.19–4.70). Low-grade toxicity was common (fatigue, pruritus, rash; q6w 46%, q3w 42%). Incidence of CSirAEs was low but low-grade toxicity was common. Despite a limited number of events, there is the suggestion that the q6w schedule has a similar toxicity profile to q3w and therefore consideration should be given to the reduced burden to patients and health services when deciding treatment.
Immune-related Bell’s palsy in melanoma patients treated with immune checkpoint inhibitors
Authors: Beninato Teresa , Fucà Giovanni , Di Guardo Lorenza , Vetrano Irene , Valeri Barbara , Nesa Francesco , Del Vecchio Michele , Cimminiello Carolina
Published: January 2021

Immune-checkpoint inhibitors (ICIs) exposed the oncology community to novel immune-related adverse events (irAEs). Here, we report on a retrospective analysis of patients with melanoma who developed an ICI-related, unilateral, acute and peripheral facial nerve paralysis (Bell’s palsy).We retrospectively reviewed all the cases of ICI-related Bell’s palsy in patients with melanoma treated at our institution from January 2015 to January 2020. A total of five cases of ICI-related Bell’s palsy were identified. Median age was 63 years. Median time-to-onset of Bell’s palsy from ICIs initiation was 15 weeks. Four patients were treated with prednisone alone, whereas one patient was treated with prednisone plus valaciclovir. All the patients completely recovered from Bell’s palsy without neurological sequelae. In melanoma patients treated with ICIs, Bell’s palsy is a rare, neurologic irAE with a favorable outcome following administration of oral corticosteroids.
Alterations of amygdala-prefrontal cortical coupling and attention deficit/hyperactivity disorder-like behaviors induced by neonatal habenula lesion: normalization by Ecklonia stolonifera extract and its active compound fucosterol
Authors: Kim Ye-Jin , Jeon So-Yeon , Choi Jae-Sue , Kim Na-Hyun , Goto Yukiori , Lee Young-A
Published: January 2021

Alterations of monoamine transmission in mesocorticolimbic regions have been suggested in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). The habenula is an important brain area in regulation of monoamine transmission. In this study, we investigated behavioral and electrophysiological alterations induced by neonatal habenula lesion (NHL) in rats. In NHL rats, age-dependent behavioral alterations relevant to the ADHD symptoms, such as hyperlocomotion, impulsivity, and attention deficit, were observed. Local field potentials (LFPs) in mesocorticolimbic regions of anesthetized rats were examined with in vivo electrophysiological recordings. Abnormally enhanced synchronization of slow (delta) and fast (gamma) LFP oscillations between the amygdala (AMY) and prefrontal cortex (PFC) was found in juvenile, but not in adult, NHL rats. We further examined the effects of an extract and the active compound from the perennial large brown algae Ecklonia stolonifera (ES), which have previously been demonstrated to modulate monoamine transmission, on these NHL-induced alterations. One week of ES extract treatments normalized the NHL-induced behavioral alterations, whereas the active compound fucosterol improved attention deficit and impulsivity, but not hyperlocomotion, in NHL rats. Consistent with the behavioral effects, ES extract treatments also normalized augmented AMY-PFC coupling. These results suggest that altered limbic-cortical information processing may be involved in ADHD-like behavioral alterations induced by NHL, which could be ameliorated by the natural substance, such as ES that affects monoamine transmission.
New strategies for the management of ocular surface disease in glaucoma patients
Authors: Voicu Laura , Salim Sarwat
Published: January 2021

Purpose of review

Glaucoma patients commonly suffer from ocular surface disease (OSD). As treatment strategies, medications and devices for the treatment of OSD as well as glaucoma surgical approaches evolve rapidly, it is important to consider their application to these patients.

Recent findings

OSD in glaucoma patients may lead to reduced reliability of diagnostic tests, decreased medication compliance, poor surgical outcomes, and overall decreased quality of life. Chronic use of topical glaucoma medications has been linked to the development of limbal stem cell deficiency, and the role of preservatives in OSD continues to be demonstrated. Preservative free glaucoma medications as well as new anti-inflammatory agents for the treatment of OSD are now available. Omega-3 fatty acid supplementation and punctal plugs have been shown to benefit glaucoma patients with OSD. Drop burden may be reduced through the use of the new sustained-release delivery systems, selective laser trabeculoplasty, and minimally invasive glaucoma surgery.

There are multiple emerging strategies for managing OSD that may be applied to patients with glaucoma. With continued research and clinical experiences, we hope to better understand the multifaceted relationship between glaucoma and OSD and develop evidence-based algorithms for the management of these complex patients.
Late onset of microbial keratitis after laser in situ keratomileusis surgery: case series
Authors: Garcerant Daniel , Cabrera-Aguas Maria , Khoo Pauline , Watson Stephanie L.
Published: January 2021

Purpose:

To report predisposing factors, clinical features, microbiology spectrum, antibiotic resistance, antimicrobial therapy, and outcomes of patients with a previous laser in situ keratomileusis (LASIK) surgery and diagnosed with presumed microbial keratitis.

Setting:

Sydney Eye Hospital, Sydney, New South Wales, Australia.

Design:

Retrospective case review.

Methods:

Patients were identified from pathology and hospital coding data from 2012 to 2016. Inclusion criteria were all patients with a previous LASIK surgery, a presumed diagnosis of microbial keratitis, and a corneal scrape performed and aged older than 18 years. Demographics, clinical details, and outcomes were collated from the medical records.

Results:

Sixteen patients were included, with median age of 41.5 years (range 22 to 85 years) and 56.2% of women. The median time between LASIK procedure and microbial keratitis presentation was 38.3 months (interquartile range 6.7 to 77.45 months). Cultures were positive for bacteria in 12 (75%) of 16 scrapes. Of the bacterial isolates, 12 (85.7%) were gram-positive and 2 (14.3%) gram-negative. Sensitivity profiles for the isolated bacteria were similar between fortified antibiotics (cefalotin and gentamicin) and commercial products (chloramphenicol and ofloxacin). Complications included the need for tectonic grafts, nonhealing epithelial defects, thinning, and neovascularization.

Conclusions:

Late onset of keratitis after LASIK can occur with no positive cultures for nontuberculous mycobacteria, no interface involvement, and no other usual features reported in case series of infectious keratitis in LASIK patients. It has a similar clinical course to non-LASIK keratitis, such that the surgery may not have been a risk factor for infection.
Agreement and variability of subjective refraction, autorefraction, and wavefront aberrometry in pseudophakic patients
Authors: Ruiss Manuel , Findl Oliver , Draschl Petra , Harrer-Seely Annette , Hirnschall Nino
Published: January 2021

Purpose:

To evaluate the comparability and variability of subjective refraction (SR), autorefraction (AR), and wavefront aberrometry (WA) in pseudophakic patients.

Setting:

Hanusch Hospital, Vienna, Austria.

Design:

Prospective study.

Methods:

Subjective refraction was performed by 2 independent examiners at 2 study visits. Furthermore, 5 measurements of AR and WA were performed in each patient at both visits. Agreement between the 3 refraction methods for spherical equivalent (M) and cylindrical vectors (J0, J45) was analyzed using Friedman multiple comparison and Bland-Altman plots. Predictability of spherical equivalent determined by SR from AR and WA measurements was tested with partial least squares regression and random forest regression.

Results:

Ninety eyes of 90 pseudophakic patients were measured. The mean absolute error and arithmetic mean difference of SR measurements of M, J0, and J45 were comparable between both examiners. A small mean difference was found for SR between both visits. Spherical equivalent was more negative when measured by AR [−0.87 diopters (D)] and WA (−0.90 D) compared with SR (−0.60 D), whereas astigmatic vectors agreed well. Good test-retest reliability was found between all 3 refraction methods for M, J0, and J45. Partial least squares regression and random forest regression showed moderate predictive power for M measured by objective refraction and SR.

Conclusions:

Reproducibility and reliability of SR measurements in pseudophakic patients showed good agreement. AR and WA measured the spherical equivalent more myopic than SR, whereas astigmatic vectors were comparable between the 3 methods after uneventful cataract surgery.
Informational Gaps, Needs, and Preferences of Adults With Chronic Health Conditions and Their Family Caregivers
Authors: Tofthagen Cindy , Chesak Sherry , Rhudy Lori , Krecke Catherine , Gaugler Joseph E.
Published: January 2021

The purpose of this cross-sectional, qualitative study was to determine unmet educational needs, preferences, and barriers experienced by individuals with chronic illness and their caregivers. A survey containing fixed-choice selections and open-ended questions was sent to persons with cancer and other chronic diseases who had been seen within a large national private health system. Between 20% and 25% of participants had difficulty obtaining health care information and/or felt overwhelmed with managing their condition. Coping, managing symptoms, and making treatment decisions were areas of need in both patients and caregivers. Preferences for receiving information were diverse. Existing methods of communication including secure Web sites where patients can access their medical records posed significant challenges.
Contributions of Airway Stent for Long-term Outcome in Patients With Malignant Central Airway Stenosis or Obstruction
Authors: Iyoda Akira , Azuma Yoko , Sano Atsushi , Sakai Takashi , Koezuka Satoshi , Otsuka Hajime , Tochigi Naobumi , Isobe Kazutoshi , Sakamoto Susumu , Takagi Keigo
Published: January 2021

Background:

Although an airway stent is used for malignant central airway stenosis or obstruction, long-term outcomes are unknown. In this study, we retrospectively analyzed the clinical features of patients who required stenting for malignant central airway stenosis or obstruction.

Patients and Methods:

We retrospectively analyzed clinical data from 116 patients with stenting for central airway stenosis or obstruction who underwent treatment at Toho University Hospital from 1998 to 2018. We evaluated the clinical features, prognoses, and complications for stenting in these patients.

Results:

The distribution of the 116 patients was as follows: lung cancer, 53; esophageal cancer, 40; thyroid cancer, 8; and others, 15. Patients with thyroid cancer had a significantly higher rate of complications after stenting than patients with lung cancer (P=0.0062), esophageal cancer (P=0.0029), and others (P=0.0062). Patients with esophageal cancer had a significantly worse prognosis than patients with lung and thyroid cancer. In patients with lung cancer the prognosis was significantly different between patients who underwent additional treatment for lung cancer after stenting and patients with no treatment (P=0.0398), and patients who received chemoradiotherapy for lung cancer after stenting had a significantly better prognosis than patients with no treatment (P=0.0306).

Conclusion:

Stenting for airway stenosis/obstruction may improve prognosis in patients with lung or thyroid cancer, especially if patients with lung cancer undergo additional treatments after stenting, although airway stenting for patients with esophageal cancer was palliative. New treatment strategies may be necessary for patients with esophageal cancer after stenting to improve prognosis.
Fluorescent Detection of Vestibular Schwannoma Using Intravenous Sodium Fluorescein In Vivo
Authors: Szczupak Mikhaylo , Peña Stefanie A. , Bracho Olena , Mei Christine , Bas Esperanza , Fernandez-Valle Cristina , Liu Xue-Zhong , Telischi Fred F. , Ivan Michael , Dinh Christine T.
Published: January 2021

Background:

Vestibular schwannoma (VS) are intracranial tumors caused by merlin deficiency. Sodium fluorescein (SF) is a fluorescent compound that accumulates in various intracranial tumors, causing tumors to emit green fluorescence after blue light excitation.

Hypothesis:

Intravenous SF preferentially deposits in VS, helping surgeons differentiate tumor from surrounding tissue.

Methods:

Merlin-deficient Schwann cells were grafted onto cochleovestibular nerves of immunodeficient rats. Rats were randomized to receive SF (7.5 mg/kg; n = 5) or saline (n = 3). Tissues were harvested at 1 hour and photographed in white and blue light. Sixteen surgeons identified and marked the tumor-tissue interfaces on images. Fluorescence was measured on tissue specimens using the IVIS imaging system and on tissue cross-sections obtained with confocal microscopy. Western blot was performed to measure levels of organic anion transporting polypeptide (OATP), a drug transporter specific for SF.

Results:

Under blue light, tumors from SF rats demonstrated bright green fluorescence under direct visualization, higher fluorescence measurements on tissue specimens (p < 0.001), and more SF deposition on tissue cross-sections (p < 0.001), when compared with surrounding tissues and placebo rats. Surgeons were better able to distinguish the tumor-tissue interfaces in SF rats. Furthermore, the expression level of OATP1C1 was significantly higher in tumors than in surrounding tissues (p < 0.0001).

Conclusion:

In a xenograft model of VS, intravenous SF preferentially deposits in tumors, compared with normal surrounding tissue. Under blue light, tumors emit an intense green fluorescence that can help surgeons differentiate tumor from critical structures nearby, which may improve clinical outcomes in complicated VS surgery.
Beyond Frontiers: Feasibility and Outcomes of Prolonged Veno-Venous Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Distress Syndrome
Authors: Rabie Ahmed A. , Asiri Ayed , Rajab Mostafa , Mufti Hani N. , Alsherbiny Medhat , Azzam Mohamed H. , Abdelbary Akram , Zakhary Bishoy , Arabi Yaseen , Alharthy Abdulrahman , Futaih Mohamed , Sobhy Mohamed , Alenazi Ismael , Bafaqeeh Fahad
Published: January 2021

Extracorporeal membrane oxygenation (ECMO) use in acute respiratory failure is increasing. We aim to compare characteristics and outcomes of patients with prolonged (≥21 days) veno-venous (VV) ECMO runs (pECMO), to patients with short (<21 days) VV ECMO runs (sECMO). The observational retrospective single-center study compared patients who received VV ECMO from January 2018 to June 2019 at Prince Mohamed Bin Abdulaziz Center in Riyadh, Saudi Arabia. Forty-three patients were supported with VV ECMO during the study period, of whom 37 are included as six patients were still receiving ECMO at time of data collection: 24 sECMO and 13 pECMO patients. Baseline characteristics and comorbidities were similar except pECMO patients were older and had a lower P/F ratio (61 [58–68] vs. 71[58–85.5], p = 0.05). Survival to hospital discharge (69% vs. 83%, p = 0.32; pECMO vs. sECMO) and 90 day survival (62% vs. 75%, p = 0.413; pECMO vs. sECMO) were similar among groups. At 1 year follow-up, all patients were still alive and independently functioning except for one patient in the pECMO group who required a walking aid related to trauma. In this single-center study, patients requiring pECMO had similar short- and long-term survival to those requiring sECMO duration.
The Use of Venovenous Extracorporeal Membrane Oxygenation in COVID-19 Infection: One Region’s Comprehensive Experience
Authors: Bergman Zachary R. , Wothe Jillian K. , Alwan Fatima S. , Dunn Alex , Lusczek Elizabeth R. , Lofrano Arianna E. , Tointon Kelly M. , Doucette Melissa , Bohman John K. , Saavedra-Romero Ramiro , Prekker Matthew E. , Brunsvold Melissa E.
Published: January 2021

Severe acute respiratory distress syndrome (ARDS) unresponsive to conventional intensive care unit (ICU) management is an accepted indication for venovenous extracorporeal membrane oxygenation (V-V ECMO) support. The frequency with which patients with coronavirus disease 2019 (COVID-19) pneumonia are selected for V-V ECMO has not been described. This was a cohort study including all patients placed on either V-V ECMO or venoarteriovenous ECMO at the four adult ECMO Centers of Excellence. Primary outcomes evaluated were survival to decannulation from the ECMO circuit, survival to discharge, and 60-day survival. Secondary outcomes were hospital length of stay (LOS), ICU LOS, length of ECMO cannulation, and length of intubation. During the study period, which corresponded to the first surge in COVID-19 hospitalizations in Minnesota, 35 patients with ARDS were selected for V-V ECMO support out of 1,849 adult ICU patients with COVID-19 infection in the state (1.9% incidence; 95% CI, 1.3–2.6%). This represents 46 (95% CI, 34–61) expected V-V ECMO patients per 100,000 confirmed positive cases of COVID-19. Twenty-six of the 35 patients (74.3%) supported with V-V ECMO survived to 60-day post-ECMO decannulation. Recent studies have demonstrated ongoing success rescuing patients with severe ARDS in COVID-19 infection. Our data add to the support of ECMO and the consideration for encouraging cooperation among regional ECMO centers to ensure access to this highest level of care. Finally, by evaluating all the patients of a single region, we estimate overall need for this resource intensive intervention based on the overall number of COVID-19 cases and ICU admissions.
Therapeutic approaches targeting splicing factor mutations in myelodysplastic syndromes and acute myeloid leukemia
Authors: Figg John W. , Barajas Juan M. , Obeng Esther A.
Published: January 2021

Purpose of review

Mutations in components of the spliceosome are the most common acquired lesions in myelodysplastic syndromes (MDS) and are frequently identified in other myeloid malignancies with a high rate of progression to acute myeloid leukemia (AML) including chronic myelomonocytic leukemia and primary myelofibrosis. The only curative option for these disorders remains allogeneic stem-cell transplantation, which is associated with high morbidity and mortality in these patients. The purpose of this review is to highlight the recent therapeutic developments and strategies being pursued for clinical benefit in splicing factor mutant myeloid malignancies.

Recent findings

Cells harboring splicing factor mutations have increased aberrant splicing leading to R-loop formation and cell cycle stalling that create dependencies on Checkpoint kinase 1 (CHK1) activation and canonical splicing maintained by protein arginine methyltransferase activity. Both targeting of the spliceosome and targeting of the downstream consequences of splicing factor mutation expression show promise as selective strategies for the treatment of splicing factor-mutant myeloid malignancies.

An improved understanding of the therapeutic vulnerabilities in splicing factor-mutant MDS and AML has led to the development of clinical trials of small molecule inhibitors that target the spliceosome, ataxia telangectasia and Rad3 related (ATR)-CHK1 pathway, and methylation of splicing components.
Telemedicine in neonatal medicine and resuscitation
Authors: Lapcharoensap Wannasiri , Lund Kelli , Huynh Trang
Published: January 2021

Purpose of review

Telehealth in neonatology is a rapidly expanding modality for providing care to neonatal patient populations. In this review, we describe the most recent published innovations in neonatal telehealth, spanning the neonatal ICU (NICU), community/rural hospitals and the patient's home.

Recent findings

Telemedicine for neonatal subspecialty care has continued to expand, from well established uses in retinopathy of prematurity screening and tele-echocardiography, to applications in genetics and neurology. Within the NICU itself, neonatologist-led remote rounding has been shown to be a feasible method of increasing access to expert care for neonates in rural hospitals. Telehealth has improved parental and caregiver education, eased the NICU-to-home transition experience and expanded access to lactation services for rural mothers. Telemedicine-assisted neonatal resuscitation has improved the quality of resuscitation and reduced unnecessary neonatal transports to higher levels of care. Finally, the global COVID-19 pandemic has accelerated the expansion of neonatal telehealth.

Telehealth provides increased access to expert neonatal care and improves patient outcomes, while reducing the cost of care for neonates in diverse settings. Continued high-quality investigation of the impacts of telehealth on patient outcomes and healthcare systems is critical to the continued development of neonatal telemedicine best practices.
Lifetime Medical Costs of Genital Herpes in the United States: Estimates From Insurance Claims
Authors: Eppink Samuel T. , Kumar Sagar , Miele Kathryn , Chesson Harrell W.
Published: January 2021

Background

The purpose of this study was to estimate the lifetime direct medical costs per incident case of genital herpes in the United States.

Methods

We used medical claims data to construct a cohort of people continuously enrolled in insurance for at least 48 consecutive months between 2010 and 2018. From this cohort, we identified initial genital herpes diagnoses as well as the cost of related clinical visits and medication during the 36 months after an initial diagnosis. Lifetime costs beyond 36 months were estimated based on treatment use patterns observed in the 36 months of follow-up.

Results

The present value of lifetime direct medical costs of genital herpes was estimated to be $972 per treated case or $165 per infection (2019 dollars), not including costs associated with prevention or treatment of neonatal herpes. The clinical visit at which genital herpes was first diagnosed accounted for 27% of lifetime costs. Subsequent clinical visits and medications related to genital herpes accounted for an additional 13% and 60% of lifetime costs, respectively.

Conclusions

The results from this study can inform cost-effectiveness analysis of genital herpes control interventions as well as help quantify the cost burden of sexually transmitted infections in the United States.
Imaging for Pediatric Blunt Abdominal Trauma With Different Prediction Rules
Authors: Ozcan Ali , Ahn Terrie , Akay Begum , Menoch Margaret
Published: January 2021

Background

Computerized tomography (CT) of the abdomen and pelvis is the standard imaging modality to diagnose intra-abdominal injury (IAI). Clinicians must weigh the risk-benefit of CT compared with the degree of clinical suspicion for an IAI. Pediatric Emergency Care Applied Research Network (PECARN), Streck, and blunt abdominal trauma in children (BATiC) prediction rules have been published to help guide evaluation of these patients. Pediatric Emergency Care Applied Research Network uses history and physical examination findings, whereas Streck and BATiC use examination plus laboratory and imaging findings. At the time of the study, there was not a protocol that was more routinely sited. Our goal was to compare these different prediction rules.

Methods

This was a retrospective electronic chart review of all children younger than 18 years presenting for either level 1 or 2 trauma activations at our pediatric emergency department (ED) between June 1, 2015, to June 30, 2017. Charts were manually reviewed for a mechanism concerning for abdominal trauma, and demographic data, history and physical examination findings, laboratory and imaging results per prediction rules, and revisits in 7 days were collected.

The prediction rules were applied to all charts that had all data necessary. For study purposes, a score of zero for PECARN and Streck, and score of ≤5 for modified BATiC (mBATiC) were defined as “low risk.” Patients with no CT, negative CT, and no new injury found on revisit were classified as “no IAI identified,” and patients with positive CT or revisit with injury found as “IAI identified.” The results were compared via Fisher exact test.

Results

A total of 249 patients met the inclusion criteria with a median age of 12 years. Of the low-risk patients, 119 (98.7%) of 121 in PECARN group, 21 (100%) of 21 in Streck, and 48 (85.7%) of 56 in mBATiC group had no IAI identified. None of the low-risk patients required any intra-abdominal intervention. No missed IAI was identified during revisit review. Negative predictive values of all 3 rules were significant for PECARN, Streck, and mBATiC (98.35%, 100%, and 85.71%, respectively). Overall, 27 patients had positive CT results for IAI.

Conclusions

The PECARN and Streck rules have high negative predictive values to predict low-risk patients who do not require CT. When laboratory studies are not obtained, PECARN is an effective means of excluding IAI for low-risk patients. When laboratory tests were obtained, the Streck rule performed well. Overall, the results are similar to the past individual studies done on each individual rule. History and physical examination findings are of high importance in pediatric trauma. This study supports limited imaging when no abnormal findings are present in children with blunt torso trauma. This is the only study found in the literature that has compared 3 different prediction rules.
Consumer Engagement With Information on Performance: A Narrative Review
Authors: Raj Minakshi , Banaszak-Holl Jane
Published: January 2021

Background and Objectives:

Efforts to provide information on quality of providers assume that consumers and patients are able to use information effectively to guide their decisions. We conducted a narrative literature review to better understand how consumers use information on quality to ultimately select a provider.

Methods:

We used Berwick's Pathways to Quality Improvement Framework to guide a narrative literature review to synthesize past research on consumer choice and to identify and evaluate factors affecting provider selection.

Results:

Reviewed articles reflected factors affecting provider selection, including: information needs, content and delivery of information, use and engagement with information, and social and behavioral mechanisms, such as trust. We also identified gaps in the literature for further study (eg, loyalty to physicians) that have been identified as important for optimal decision-making but are not well explored in the literature.

Discussion:

Health care providers and managers can learn from a more complete model of consumers' selection process to systematically evaluate and improve service provision and information for consumers. Administrators and providers may consider using patient feedback to identify ways to improve their quality and should streamline information for consumers to facilitate thorough, informed decision-making.
Graphic Representation of Hourly Activity Counts May Identify Discharge Outcomes for Older Adults After Critical Illness
Authors: Elías Maya N. , Munro Cindy L. , Liang Zhan
Published: January 2021

Purpose

After transitioning from an intensive care unit (ICU), hospitalized older adults are inactive, which may affect discharge outcomes. We examined trends between post-ICU hourly activity counts and discharge disposition among hospitalized older ICU survivors.

Design

A prospective, exploratory research design was used in this study.

Methods

We enrolled older ICU survivors within 24–48 hours of ICU discharge. Actigraphy measured post-ICU hourly activity counts (0:00 a.m.–23:59 p.m.). Chart review provided discharge disposition. Analyses were conducted to illustrate trends between post-ICU hourly activity counts and discharge disposition.

Findings

Mean hourly activity was about 2,233 ± 569 counts/hour. Graphs revealed trends between hourly activity counts and discharge disposition. Participants with lower post-ICU activity counts, especially during daytime hours, tended to be discharged to a care facility.

Conclusions

Future nursing research should determine whether post-ICU inactivity during hospitalization is a modifiable risk factor for worse discharge outcomes.

Clinical Relevance

Activity could be a prognostic indicator of discharge disposition for older ICU survivors.
Association Between Blood Donor Demographics and Post-injury Multiple Organ Failure after Polytrauma
Authors: Amico Francesco , Efird Jimmy T. , Briggs Gabrielle D. , Lott Natalie J. , King Kate L. , Hirani Rena , Balogh Zsolt J.
Published: January 2021

Objective:

To test the hypothesis that blood donor demographics are associated with transfused polytrauma patients’ post-injury multiple organ failure (MOF) status.

Summary of Background Data:

Traumatic shock and MOF are preventable causes of death and post-traumatic hemorrhage is a frequent indication for transfusion. The role of blood donor demographics on transfusion recipients is not well known.

Methods:

A log-linear analysis accounting for the correlated structure of the data based on our prospective MOF database was utilized. Tests for trend and interaction were computed using a likelihood ratio procedure.

Results:

A total of 229 critically injured transfused trauma patients were included, with 68% of them being males and a mean age of 45 years. On average 10 units of blood components were transfused per patient. A total of 4379 units of blood components were donated by donors aged 46 years on average, 74% of whom were males. Blood components used were red blood cells (47%), cryoprecipitate (29%), fresh frozen plasma (24%), and platelets (less than 1%). Donor-recipient sex mismatched red blood cells transfusions were more likely to be associated with MOF (P = 0.0012); fresh frozen plasma and cryoprecipitate recipients were more likely to experience MOF when transfused with a male (vs female) component (P = 0.0014 and <0.0001, respectively). Donor age was not significantly associated with MOF for all blood components.

Conclusions:

Blood components donor sex, but not age, may be an important factor associated with post-injury MOF. Further validation of our findings will help guide future risk mitigation strategies specific to blood donor demographics.
Psychological Health of Surgeons in a Time of COVID-19
Authors: Tan Yi Quan , Wang Ziting , Yap Qai Ven , Chan Yiong Huak , Ho Roger C. , Hamid Agus Rizal Ardy Hariandy , Landaluce-Olavarria Aitor , Pellino Gianluca , Gauhar Vineet , Chand Manish , Wroclawski Marcelo Langer , Hameed BM Zeeshan , Ling Samuel Ka-Kin , Sengupta Shomik , Gallo Gaetano , Chiu Peter Ka-Fung , Tanidir Yiloren , Tallada M. Pilar Villanova , Garcia Bernardo Nunez , Colleoni Ramiro , Abiddin Zainal Adwin Zainal , Campi Riccardo , Esperto Francesco , Carrion Diego , Elterman Dean , Chung Amanda Shu Jun , Ng Anthony Chi Fai , Moschini Marco , Rivas Juan Gomez , Mayol Julio , Teoh Jeremy Yuen-Chun , Chiong Edmund ,   SoMe4Surgery working group Collaborators
Published: January 2021

Objective:

To assess the degree of psychological impact among surgical providers during the COVID-19 pandemic.

Summary of Background Data:

The COVID-19 pandemic has extensively impacted global healthcare systems. We hypothesized that the degree of psychological impact would be higher for surgical providers deployed for COVID-19 work, certain surgical specialties, and for those who knew of someone diagnosed with, or who died, of COVID-19.

Methods:

We conducted a global web-based survey to investigate the psychological impact of COVID-19. The primary outcomes were the depression anxiety stress scale-21 and Impact of Event Scale-Revised scores.

Results:

A total of 4283 participants from 101 countries responded. 32.8%, 30.8%, 25.9%, and 24.0% screened positive for depression, anxiety, stress, and PTSD respectively. Respondents who knew someone who died of COVID-19 were more likely to screen positive for depression, anxiety, stress, and PTSD (OR 1.3, 1.6, 1.4, 1.7 respectively, all P < 0.05). Respondents who knew of someone diagnosed with COVID-19 were more likely to screen positive for depression, stress, and PTSD (OR 1.2, 1.2, and 1.3 respectively, all P < 0.05). Surgical specialties that operated in the head and neck region had higher psychological distress among its surgeons. Deployment for COVID- 19-related work was not associated with increased psychological distress.

Conclusions:

The COVID-19 pandemic may have a mental health legacy outlasting its course. The long-term impact of this ongoing traumatic event underscores the importance of longitudinal mental health care for healthcare personnel, with particular attention to those who know of someone diagnosed with, or who died of COVID-19.
Linking single-cell decisions to collective behaviours in social bacteria
Authors: Dinet Céline , Michelot Alphée , Herrou Julien , Mignot Tâm
Published: January 2021

Social bacteria display complex behaviours whereby thousands of cells collectively and dramatically change their form and function in response to nutrient availability and changing environmental conditions. In this review, we focus on
Myxococcus xanthus
motility, which supports spectacular transitions based on prey availability across its life cycle. A large body of work suggests that these behaviours require sensory capacity implemented at the single-cell level. Focusing on recent genetic work on a core cellular pathway required for single-cell directional decisions, we argue that signal integration, multi-modal sensing and memory are at the root of decision making leading to multicellular behaviours. Hence,
Myxococcus
may be a powerful biological system to elucidate how cellular building blocks cooperate to form sensory multicellular assemblages, a possible origin of cognitive mechanisms in biological systems.

This article is part of the theme issue ‘Basal cognition: conceptual tools and the view from the single cell’.
Host factors abolish the need for polysaccharides and extracellular matrix-binding protein in Staphylococcus epidermidis biofilm formation
Authors: Skovdal Sandra M. , Hansen Liva Kjær , Ivarsen Diana Malskær , Zeng Guanghong , Büttner Henning , Rohde Holger , Jørgensen Nis Pedersen , Meyer Rikke L.
Published: January 2021

Introduction.

Staphylococcus epidermidis

is predominant in implant-associated infections due to its capability to form biofilms. It can deploy several strategies for biofilm development using either polysaccharide intercellular adhesin (PIA), extracellular DNA (eDNA) and/or proteins, such as the extracellular matrix-binding protein (Embp).

Hypothesis/Gap Statement. We hypothesize that the dichotomic regulation of

S. epidermidis

adhesins is linked to whether it is inside a host or not, and that in vitro biofilm investigations in laboratory media may not reflect actual biofilms in vivo.

Aim. We address the importance of PIA and Embp in biofilm grown in ‘humanized’ media to understand if these components play different roles in biofilm formation under conditions where bacteria can incorporate host proteins in the biofilm matrix.

Methodology.

S. epidermidis

1585 WT (deficient in icaADBC), and derivative strains that either lack embp, express embp from an inducible promotor, or express icaADBC from a plasmid, were cultivated in standard laboratory media, or in media with human plasma or serum. The amount, structure, elasticity and antimicrobial penetration of biofilms was quantified to describe structural differences caused by the different matrix components and growth conditions. Finally, we quantified the initiation of biofilms as suspended aggregates in response to host factors to determine how quickly the cells aggregate in response to the host environment and reach a size that protects them from phagocytosis.

Results.

S. epidermidis

1585 required polysaccharides to form biofilm in laboratory media. However, these observations were not representative of the biofilm phenotype in the presence of human plasma. If human plasma were present, polysaccharides and Embp were redundant for biofilm formation. Biofilms formed in human plasma were loosely attached and existed mostly as suspended aggregates. Aggregation occurred after 2 h of exposing cells to plasma or serum. Despite stark differences in the amount and composition of biofilms formed by polysaccharide-producing and Embp-producing strains in different media, there were no differences in vancomycin penetration or susceptibility.

Conclusion. We suggest that the assumed importance of polysaccharides for biofilm formation is an artefact from studying biofilms in laboratory media void of human matrix components. The cell–cell aggregation of

S. epidermidis

can be activated by host factors without relying on either of the major adhesins, PIA and Embp, indicating a need to revisit the basic question of how

S. epidermidis

deploys self-produced and host-derived matrix components to form antibiotic-tolerant biofilms in vivo.
Microbiology challenges and opportunities in the circular economy
Authors: O'Connor Kevin E.
Published: January 2021

Our knowledge and understanding of micro-organisms have led to the development of safe food, clean water, novel foods, antibiotics, vaccines, healthier plants, animals and soils, and more, which feeds into the United Nations Sustainable Development Goals (UN SDGs). The circular economy can contribute to the UN SDGs and micro-organisms are central to circular nutrient cycles. The circular economy as described by the Ellen MacArthur foundation has two halves, i.e. technical and biological. On the technical side, non-biological resources enter manufacturing paths where resource efficiency, renewable energy and design extend the life of materials so that they are more easily reused and recycled. Biological resources exist on the other half of the circular economy. These are used to manufacture products such as bioplastics and paper. The conservation of nature’s stocks, resource efficiency and recycling of materials are key facets of the biological half of the circular economy. Microbes play a critical role in both the biological and technical parts of the circular economy. Microbes are key to a functioning circular economy, where natural resources, including biological wastes, are converted by microbes into products of value and use for society, e.g. biogas, bioethanol, bioplastics, building block chemicals and compost for healthy soils. In more recent times, microbes have also been seen as part of the tool kit in the technical side of the circular economy, where microbial enzymes can degrade plastics and microbes can convert those monomers to value-added products.
COVID-19 Diagnostic Testing For All - Using Non-Dilutive Saliva Sample Collection, Stabilization and Ambient Transport Devices
Authors: Carrington Yuan , Orlino Justin , Romero Alejandro , Gustin Jessica , Rezaei Mahssa , Greene Elizabeth , Rose Summer , Aiyer Ramani A. , Nasarabadi Shanavaz
Published: January 2021

COVID-19 testing is not accessible for millions during this pandemic despite our best efforts. Without greatly expanded testing of asymptomatic individuals, contact tracing and subsequent isolation of spreaders remains as a means for control. In an effort to increase RT-PCR assay testing for the presence of the novel beta-coronavirus SARS-CoV-2 as well as improve sample collection safety, GenTegra LLC has introduced two products for saliva collection and viral RNA stabilization: GTR-STM™ (GenTegra Saliva Transport Medium) and GTR-STMdk™ (GenTegra Saliva Transport Medium Direct to PCR). Both products contain a proprietary formulation based on GenTegra’s novel “Active Chemical Protection™” (ACP) technology that gives non-dilutive, error-free saliva sample collection using RNA stabilization chemicals already dried in the collection tube.

GTR-STM can be used for safer saliva-based sample collection at home (or at a test site). Following saliva collection, the sample-containing GTR-STM can be kept at ambient temperature during shipment to an authorized CLIA lab for analysis. SARS-CoV-2 viral RNA in GTR-STM is stable for over a month at ambient temperature, easily surviving the longest transit times from home to lab. GTR-STM enhances patient comfort, convenience, compliance and reduces infectious virus exposure to essential medical and lab professionals.

Alternatively, the GTR-STMdk direct-into-PCR product can be used to improve lab throughput and reduce reagent costs for saliva sample collection and testing at any lab site with access to refrigeration. GTR-STMdk reduces lab process time by 25% and reagent costs by 30% compared to other approaches. Since GTR-STMdk retains SARS-CoV-2 viral RNA stability for three days at ambient temperature, it is optimized for lab test site rather than at home saliva collection. SARS-COV-2 viral RNA levels as low as 0.4 genome equivalents/uL are detected in saliva samples using GTR-STMdk. The increased sensitivity of SARS-CoV-2 detection can expand COVID-19 testing to include asymptomatic individuals using pooled saliva.

One Sentence Summary

GTR-STM and Direct-into-PCR GTR-STMdk offer substantive improvements in SARS-CoV-2 viral RNA stability, safety, and RT-PCR process efficiency for COVID-19 testing by using a non-dilutive saliva sample collection system for individuals at home or onsite respectively.
Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
Authors: Hautakangas Heidi , Winsvold Bendik S. , Ruotsalainen Sanni E. , Bjornsdottir Gyda , Harder Aster V. E. , Kogelman Lisette J. A. , Thomas Laurent F. , Noordam Raymond , Benner Christian , Gormley Padhraig , Artto Ville , Banasik Karina , Bjornsdottir Anna , Boomsma Dorret I. , Brumpton Ben M. , Sølvsten Burgdorf Kristoffer , Buring Julie E. , Chalmer Mona Ameri , de Boer Irene , Dichgans Martin , Erikstrup Christian , Färkkilä Markus , Garbrielsen Maiken Elvestad , Ghanbari Mohsen , Hagen Knut , Häppölä Paavo , Hottenga Jouke-Jan , Hrafnsdottir Maria G. , Hveem Kristian , Johnsen Marianne Bakke , Kähönen Mika , Kristoffersen Espen S. , Kurth Tobias , Lehtimäki Terho , Lighart Lannie , Magnusson Sigurdur H. , Malik Rainer , Pedersen Ole Birger , Pelzer Nadine , Penninx Brenda W. J. H. , Ran Caroline , Ridker Paul M. , Rosendaal Frits R. , Sigurdardottir Gudrun R. , Skogholt Anne Heidi , Sveinsson Olafur A. , Thorgeirsson Thorgeir E. , Ullum Henrik , Vijfhuizen Lisanne S. , Widén Elisabeth , van Dijk Ko Willems ,   International Headache Genetics Consortium, Headache HUNT All-in ,   Danish Blood Donor Study Genomic Cohort, Aromaa Arpo , Belin Andrea Carmine , Freilinger Tobias , Ikram M. Arfan , Järvelin Marjo-Riitta , Raitakari Olli T. , Terwindt Gisela M. , Kallela Mikko , Wessman Maija , Olesen Jes , Chasman Daniel I. , Nyholt Dale R. , Stefánsson Hreinn , Stefansson Kari , van den Maagdenberg Arn M. J. M. , Hansen Thomas Folkmann , Ripatti Samuli , Zwart John-Anker , Palotie Aarno , Pirinen Matti
Published: January 2021

Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. This genome-wide association study (GWAS) of 102,084 migraine cases and 771,257 controls identified 123 loci of which 86 are novel. The loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. A stratification of the risk loci using 29,679 cases with subtype information, of which approximately half have never been used in a GWAS before, indicated three risk variants that appear specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that appear specific for migraine without aura (near SPINK2 and near FECH), and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.