bluuebunny/crossref_metadata_2025 huggingface dataset:
Late-time cosmic evolution of dust: solving the puzzle
Authors: Ferrara Andrea , Peroux Celine
Published: March 2021

Dust is an essential ingredient of galaxies, determining the physical and chemical conditions in the interstellar medium. Several complementary observational evidences indicate that the cosmic dust mass density significantly drops from redshift z = 1 to z = 0. Clearly, and for the first time during cosmic evolution, dust must be destroyed more rapidly than it is formed. By considering the dust production/destruction processes acting in this cosmic time lapse, we find that the drop can be explained if dust is mainly destroyed by astration (49 per cent contribution in the fiducial case) and supernova (SN) shocks within galaxies (42 per cent). Our results further imply that on average each SN destroys only $M_{\mathrm{ d},\mathrm{ sn}} =0.45\, \mathrm{ M}_\odot$ of dust, i.e. 5–10 times less than usually assumed, with a hard upper limit of Md,sn < 3.0 M⊙ set by the available metal budget and maximal grain growth. The lower efficiency might be explained by effective shielding of dust against shock processing in pre-SN wind shells.
New insights into star cluster evolution towards energy equipartition
Authors: Pavlík Václav , Vesperini Enrico
Published: March 2021

We present the results of a study aimed at exploring the evolution towards energy equipartition in star cluster models with different initial degrees of anisotropy in the velocity distribution. Our study reveals a number of novel aspects of the cluster dynamics and shows that the rate of evolution towards energy equipartition (i) depends on the initial degree of radial velocity anisotropy – it is more rapid for more radially anisotropic systems; and (ii) differs for the radial and the tangential components of the velocity dispersion. (iii) The outermost regions of the initially isotropic system evolve towards a state of ‘inverted’ energy equipartition in which high-mass stars have a larger velocity dispersion than low-mass stars – this inversion originates from the mass dependence of the tangential velocity dispersion whereas the radial velocity dispersion shows no anomaly. Our results add new fundamental elements to the theoretical framework needed to interpret the wealth of recent and upcoming observational studies of stellar kinematics in globular clusters, and shed further light on the link between the clusters’ internal kinematics, their formation, and evolutionary history.
Demographic History, Adaptation, and NRAP Convergent Evolution at Amino Acid Residue 100 in the World Northernmost Cattle from Siberia
Authors: Buggiotti Laura , Yurchenko Andrey A , Yudin Nikolay S , Vander Jagt Christy J , Vorobieva Nadezhda V , Kusliy Mariya A , Vasiliev Sergei K , Rodionov Andrey N , Boronetskaya Oksana I , Zinovieva Natalia A , Graphodatsky Alexander S , Daetwyler Hans D , Larkin Denis M
Published: March 2021

Native cattle breeds represent an important cultural heritage. They are a reservoir of genetic variation useful for properly responding to agriculture needs in the light of ongoing climate changes. Evolutionary processes that occur in response to extreme environmental conditions could also be better understood using adapted local populations. Herein, different evolutionary histories of the world northernmost native cattle breeds from Russia were investigated. They highlighted Kholmogory as a typical taurine cattle, whereas Yakut cattle separated from European taurines approximately 5,000 years ago and contain numerous ancestral and some novel genetic variants allowing their adaptation to harsh conditions of living above the Polar Circle. Scans for selection signatures pointed to several common gene pathways related to adaptation to harsh climates in both breeds. But genes affected by selection from these pathways were mostly different. A Yakut cattle breed-specific missense mutation in a highly conserved NRAP gene represents a unique example of a young amino acid residue convergent change shared with at least 16 species of hibernating/cold-adapted mammals from six distinct phylogenetic orders. This suggests a convergent evolution event along the mammalian phylogenetic tree and fast fixation in a single isolated cattle population exposed to a harsh climate.
From grieving to healing: moving forward a year after COVID-19
Authors: Corpuz Jeff Clyde G
Published: March 2021

This paper addresses the many complex and traumatic losses brought by the coronavirus disease 2019 pandemic. During this crisis, it is important to grieve what has been lost, and it is also important to find meaning and hope in how life has changed. Conversely, there is no one size fits all formula for healing and coping with loss. Healing occurs in phases where one is moving in and out of different emotions. The saying ‘time heals all wounds’ is only partially correct because, for prolonged grief, time is not the solution.
Inhibition Kinetics of 16 Organophosphorus Pesticides or Their Active Metabolites on Erythrocyte Acetylcholinesterase From Humans and Rats
Authors: Meek Edward C , Reiss Richard , Crow John Allen , Chambers Janice E
Published: March 2021

Inhibition kinetics assays were conducted with 16 commercial organophosphate (OP) pesticides or their metabolites on acetylcholinesterase (AChE) in erythrocyte “ghost” preparations from 18 individual humans (both sexes; adults, juveniles, and cord blood samples; mixed races/ethnicities) and pooled samples from adult rats (both sexes). A well-established spectrophotometric assay using acetylthiocholine as substrate and a chromogen was employed. The kinetic parameters bimolecular rate constant (ki), dissociation constant (KI), and phosphorylation constant (kp) were calculated for each compound. As expected, a wide range of potencies were displayed among the tested compounds. Statistical analysis of the resultant data indicated no differences in sex, age, or race/ethnicity among the human samples that are unexpected based on chance (4.2% statistically significant out of 48 parameters calculated) and no differences between the sexes in rats. The bimolecular rate constants for 10 of the compounds were not statistically different between rats and humans. The data indicate that, consistent with the high level of conservation of AChE among species and the fact that AChE at different locations within a species arises from the same gene, the inhibition kinetic parameters calculated from rat erythrocyte ghost preparations should be useful in estimating potencies of OP compounds on target AChE in humans. Additionally, the data indicate that differences in sensitivities among individual humans were not apparent.
Prevalence of viral hepatitis B and C in Sierra Leone—current knowledge and knowledge gaps: a narrative review
Authors: Lakoh Sulaiman , García-Tardón Noemí , Adekanmbi Olukemi , van der Valk Marc , Smith Samuel J , Grobusch Martin P
Published: March 2021

There are no comprehensive data on viral hepatitis from Sierra Leone; however, a huge disease burden has been observed in different subpopulations. This review summarizes available data on hepatitis B and C virus (HBV and HCV) prevalence in Sierra Leone and identifies knowledge gaps. Despite the non-uniformity of the studies and the lack of systematic case recording, different reports published in recent decades yielded a hepatitis B prevalence of 8.7% among healthcare workers, 11.3% among pregnant women, 15.2% among blood donors and 16.7% in school-age children. The actual HBV prevalence in the general population was reported as 21.7%; similar to what was reported for people living with human immunodeficiency virus (PLHIV). HCV prevalence is 8% and 7% in male and female blood donors, respectively, 4.1% in PLHIV and 2.0% in school children. There are significant knowledge gaps regarding the prevalence of viral hepatitis B and C in Sierra Leone, despite the high burden reported in a few studies. There are limited programmatic interventions on the control and prevention of viral hepatitis in the country. Therefore, well-structured representative studies should provide a solid understanding of the true prevalence of hepatitis B and C to inform best possible public health measures in Sierra Leone.
Student-Led Efforts to Advance Anti-Racist Medical Education
Authors: Afolabi Titilayo , Borowsky Hannah M. , Cordero Daniella M. , Paul Dereck W. , Said Jordan Taylor , Sandoval Raquel Sofia , Davis Denise , Ölveczky Daniele , Chatterjee Avik
Published: March 2021

Over the past decade, medical schools across the United States have increasingly dedicated resources to advancing racial and social justice, such as by supporting diversity and inclusion efforts and by incorporating social medicine into the traditional medical curricula. While these changes are promising, the academic medicine community must apply an anti-racist lens to every aspect of medical education to equip trainees to recognize and address structural inequities. Notably, organizing and scholarly work led by medical students has been critical in advancing anti-racist curricula. In this article, the authors illustrate how student activism has reshaped medical education by highlighting examples of student-led efforts to advance anti-racist curricula at Harvard Medical School (HMS) and at the University of California, San Francisco (UCSF) School of Medicine. HMS students collaborated with faculty to address aspects of existing clinical practice that perpetuate racism, such as the racial correction factor in determining kidney function. They also responded to the existing curricula by noting missed opportunities to discuss structural racism, and they planned supplemental sessions to address these gaps. At UCSF, students identified specific avenues to improve the rigor of social medicine courses and developed new curricula to equip students with skills to confront and work to dismantle racism. The authors describe how HMS students, in an effort to improve the learning environment, developed a workshop to assist students in navigating microaggressions and discrimination in the clinical setting. At UCSF, students partnered with faculty and administration to advocate pass/fail grading for clerkships after university data revealed racial disparities in students’ clerkship assessments. In reviewing these examples of students’ advocacy to improve their own curricula and learning environments, the authors aim to provide support for students and faculty pursuing anti-racist curricular changes at their own institutions.
Widening of Pulley by Interdigitating Cuts
Authors: Patil Rahul , Bhandari Laxminarayan
Published: March 2021

While biomechanically important, pulleys present multiple challenges to a zone 2 flexor tendon repair and rehabilitation. Retrieval of tendon through an intact pulley is cumbersome. Following repair, venting is often needed to accommodate the bulk at repair site. On occasion, step lengthening, or even complete division of pulley and reconstruction with tendon graft are necessary. Finally, accessing the tendon under the pulley during tenolysis is difficult. The primary issue in all such cases is the lack of space under the pulley. We describe a technique of expanding the pulley by interdigitating cuts. This technique greatly increases the diameter of the pulley which could be demonstrated in cadaver model and noted in clinical setting. This technique is easy to perform and maintains the integrity of the pulley without complete division. It would allow easy tendon retrieval, provide space for the repair and gliding, and improve exposure during tenolysis.
ABCDEF Bundle and Supportive ICU Practices for Patients With Coronavirus Disease 2019 Infection: An International Point Prevalence Study
Authors: Liu Keibun , Nakamura Kensuke , Katsukawa Hajime , Elhadi Muhammed , Nydahl Peter , Ely Eugene Wesley , Kudchadkar Sapna R. , Takahashi Kunihiko , Inoue Shigeaki , Lefor Alan Kawarai , Kesecioglu Jozef , Nishida Osamu
Published: March 2021

Objectives:

To investigate implementation of evidence-based and supportive cares in ICUs, such as the ABCDEF, nutrition therapy, and ICU diary, for patients with coronavirus disease 2019 infection in ICUs and their association with ICU clinical practice and setting.

Design:

A worldwide, 2-day point prevalence study.

Setting:

The study was carried out on June 3, 2020, and July 1, 2020. A total of 212 ICUs in 38 countries participated. Clinicians in each participating ICU completed web-based online surveys.

Patients:

The ICU patients with coronavirus disease 2019.

Interventions:

None.

Measurements and Main results:

The implementation rate for the elements of the ABCDEF bundle, other supportive ICU care measures, and implementation-associated structures were investigated. Data were collected for 262 patients, of whom 47.3% underwent mechanical ventilation and 4.6% were treated with extracorporeal membrane oxygenation. Each element was implemented for the following percentages of patients: elements A (regular pain assessment), 45%; B (both spontaneous awakening and breathing trials), 28%; C (regular sedation assessment), 52%; D (regular delirium assessment), 35%; E (early mobility and exercise), 47%; and F (family engagement and empowerment), 16%. The implementation of element E was 4% for patients on mechanical ventilation and 8% for patients on extracorporeal membrane oxygenation. Supportive care, such as protein provision throughout the ICU stay (under 1.2 g/kg for more than 50% of the patients) and introduction of ICU diary (25%), was infrequent. Implementation rates of elements A and D were higher in ICUs with specific protocols and fewer ICU beds exclusively for patients with coronavirus disease 2019 infection. Element E was implemented at a higher rate in ICUs that had more ICU beds assigned for them.

Conclusions:

This point prevalence study showed low implementation of the ABCDEF bundle. Specific protocols and the number of ICU beds reserved for patients with coronavirus disease 2019 infection might be key factors for delivering appropriate supportive care.
Rapid Development of a Tool for Prioritizing Patients with Coronavirus Disease 2019 for Intensive Care
Authors: Roy Melyssa , Hansen Paul , Sullivan Trudy , Ombler Franz , Kiore Mathew , Stapleton Andrew , Carr Craig
Published: March 2021

Objectives:

To explain and demonstrate a new approach for rapidly developing a decision-support tool for prioritizing patients with coronovirus 2019 disease for admission to ICUs.

Design:

An expert group used multi-criteria decision analysis methods to specify criteria and weights, representing their relative importance, for prioritizing patients with coronovirus 2019 disease with respect to likely clinical benefit. Specialized multi-criteria decision analysis software, implementing the “Potentially All Pairwise RanKings of all possible Alternatives” method to determine the weights, was used. Social equity considerations for prioritizing patients were also identified as important.

Setting:

The prioritization tool was developed in New Zealand.

Subjects:

An expert group comprising specialists from intensive care medicine and nursing, Māori (New Zealand’s indigenous population) health, infectious diseases, and neonatology was formed. The group’s work was supported by health economists and decision analysts and overseen by an ethicist and a senior representative from the New Zealand Ministry of Health.

Interventions:

Multi-criteria decision analysis to create a prioritization tool.

Measurements and Main Results:

The prioritization tool comprised eight criteria with respect to likely clinical benefit. In decreasing order of importance (weights in parentheses): Sequential Organ Failure Assessment score (15.7%), preexisting cardiovascular conditions (15.7%), functional capacity (15.7%), age (12.4%), preexisting respiratory conditions (11.1%), immunocompromised (11.1%), body mass index (9.2%), and other relevant medical conditions (9.2%). Two social equity considerations were also included in the overarching decision framework to be used alongside the clinical criteria: prioritizing Māori and Pacific people (and, potentially, other at-risk groups), and healthcare and other frontline workers.

Conclusions:

The criteria and weights in the prioritization tool can be easily revised as new evidence emerges. The approach for developing the tool could be used in other countries whose ICUs are at risk of being overwhelmed by the coronavirus disease 2019 pandemic to rapidly develop their own prioritization tools. In the event that future crises threaten to overload ICUs, other prioritization tools could also be rapidly developed.
RNA therapeutics for cardiovascular disease
Authors: Boada Christian , Sukhovershin Roman , Pettigrew Roderic , Cooke John P.
Published: March 2021

Purpose of review

The development of mRNA vaccines against coronavirus disease 2019 has brought worldwide attention to the transformative potential of RNA-based therapeutics. The latter is essentially biological software that can be rapidly designed and generated, with an extensive catalog of applications. This review aims to highlight the mechanisms of action by which RNA-based drugs can affect specific gene targets and how RNA drugs can be employed to treat cardiovascular disease, with the focus on the therapeutics being evaluated in clinical trials. The recent advances in nanotechnology aiding the translation of such therapies into the clinic are also discussed.

Recent findings

There is a growing body of studies demonstrating utility of RNA for targeting previously ‘undruggable’ pathways involved in development and progression of cardiovascular disease. Some challenges in RNA delivery have been overcome thanks to nanotechnology. There are several RNA-based drugs to treat hypercholesterolemia and myocardial infarction which are currently in clinical trials.

RNA therapeutics is a rapidly emerging field of biotherapeutics based upon a powerful and versatile platform with a nearly unlimited capacity to address unmet clinical needs. These therapeutics are destined to change the standard of care for many diseases, including cardiovascular disease.
Protective effect of controlled blood pressure on risk of dementia in low-risk, grade 1 hypertension
Authors: Lee Chan Joo , Hwang Jinseub , Kang Chae Young , Kim Hyeon-Chang , Ryu Dong-Ryeol , Ihm Sang-Hyun , Kim Yong-Jin , Shin Jin-Ho , Pyun Wook Bum , Kim Changsoo , Park Sungha
Published: March 2021

Objective:

High blood pressure (BP) increases the risk of dementia; however, few studies have reported on the risk of dementia in patients with low-risk, early-grade hypertension. We investigated the protective effect of controlled BP on risk of dementia in treated, low-risk, grade 1 hypertensive patients from the entire National Health Insurance Service National Health Examinee cohort.

Methods:

We selected grade 1 hypertension (140–159/90–99 mmHg) patients with low risk, diagnosed in 2005–2006. All patients (N = 128 665) were classified into controlled (average BP < 140/90 mmHg during the follow-up) and uncontrolled (average BP ≥ 140/90 mmHg) BP groups and followed up until 2015. The risk of dementia was estimated using Cox proportional hazard model after adjustments for propensity score.

Results:

Average BP was 131/81 mmHg in the controlled group (N = 49 408) and 144/87 mmHg in the uncontrolled group (N = 99 257). Overall dementia incidence rates in controlled and uncontrolled groups were 4.9 and 8.1 per 1000 person-year, respectively. The controlled group showed lower risk of overall dementia, Alzheimer's disease, and vascular dementia than the uncontrolled group. The controlled group had a low risk of vascular dementia at all ages, especially in the younger group (age <60). The optimal BP level associated with the lowest risk of dementia was 130 to less than 140 mmHg for SBP and 70 to less than 80 mmHg for DBP.

Conclusion:

We concluded that among even low-risk and grade 1 hypertension patients, controlled BP significantly reduced the risk of dementia, including Alzheimer's disease and vascular dementia.
Blood pressure levels and risk of haemorrhagic stroke in patients with atrial fibrillation and oral anticoagulants: results from The Swedish Primary Care Cardiovascular Database of Skaraborg
Authors: Bager Johan-Emil , Hjerpe Per , Schiöler Linus , Bengtsson Boström Kristina , Kahan Thomas , Ödesjö Helena , Jood Katarina , Hasselström Jan , Ljungman Charlotta , Manhem Karin , Mourtzinis Georgios
Published: March 2021

Objective:

To assess the risk of haemorrhagic stroke at different baseline SBP levels in a primary care population with hypertension, atrial fibrillation and newly initiated oral anticoagulants (OACs).

Methods:

We identified 3972 patients with hypertension, atrial fibrillation and newly initiated OAC in The Swedish Primary Care Cardiovascular Database of Skaraborg. Patients were followed from 1 January 2006 until a first event of haemorrhagic stroke, death, cessation of OAC or 31 December 2016. We analysed the association between continuous SBP and haemorrhagic stroke with a multivariable Cox regression model and plotted the hazard ratio as a function of SBP with a restricted cubic spline with 130 mmHg as reference.

Results:

There were 40 cases of haemorrhagic stroke during follow-up. Baseline SBP in the 145–180 mmHg range was associated with a more than doubled risk of haemorrhagic stroke, compared with a SBP of 130 mmHg.

Conclusion:

In this cohort of primary care patients with hypertension and atrial fibrillation, we found that baseline SBP in the 145–180 mmHg range, prior to initiation of OAC, was associated with a more than doubled risk of haemorrhagic stroke, as compared with an SBP of 130 mmHg. This suggests that lowering SBP to below 145 mmHg, prior to initiation of OAC, may decrease the risk of haemorrhagic stroke in patients with hypertension and atrial fibrillation.
Light therapy improves diurnal blood pressure control in night shift workers via reduction of catecholamines: the EuRhythDia study
Authors: Hannemann Juliane , Laing Anika , Middleton Benita , Cridland Jonathan , Staels Bart , Marx Nikolaus , Grant Peter J. , Federici Massimo , Stenberg Tarja , Skene Debra J. , Böger Rainer
Published: March 2021

Objectives:

Night shift work is associated with high rates of hypertension and cardiometabolic disease, which are linked to disrupted circadian rhythms. We hypothesized that timed light therapy might improve disrupted circadian rhythms and stabilize diurnal control of blood pressure and glucose in night shift workers.

Methods:

We randomized 24 rotating night shift workers (mean age, 36 ± 13 years, 7 men) who had spent a median of 6 years on rotating night shifts (median, six night shifts per month) to 12 weeks of light therapy or no intervention and compared them with 12 daytime workers (37 ± 11 years, 6 men). We measured oral glucose tolerance (OGTT), 24-h blood pressure and arterial stiffness, and the circadian profiles of melatonin, cortisol, metanephrine and nor-metanephrine at baseline, after 12 weeks of intervention, and 12 weeks after the end of intervention.

Results:

At baseline, fewer night shift workers showed dipper status as compared with daytime workers (29 vs. 58%; P < 0.001). After 12 weeks of light therapy, there was a highly significant increase in the proportion of dippers (to 58%; P < 0.0001). We also observed a significant decrease in serum glucose during OGTT in the light therapy group (−22%; P < 0.05) with no change in serum insulin. Whilst circadian profiles of melatonin and cortisol were unchanged, plasma metanephrine and nor-metanephrine levels were significantly reduced in the light therapy group (P < 0.01).

Conclusion:

Timed light therapy improves diurnal blood pressure control and glucose tolerance in rotating night shift workers. This effect is unrelated to melatonin and cortisol but is paralleled by reduced catecholamine levels.
Current treatment strategies for symptomatic vitreous opacities
Authors: Ryan Edwin H.
Published: March 2021

Purpose of review

Symptomatic vitreous opacities are increasingly recognized as a significant burden to patient well-being. There is growing interest in the use of vitrectomy or laser treatment to address these problems. This review is intended to update current assessment, management, and risks of treatment for persistent severely symptomatic vitreous opacities.

Recent findings

Despite studies showing the value of quantitative ultrasound, reading speed measurements, and contrast sensitivity for assessing dysfunction caused by vitreous opacities, the decision of whether to proceed with surgery remains a very subjective, clinical one. Visual Function Questionnaire-25 score studies show a very large improvement postvitrectomy consistent with relief from symptoms and patient satisfaction. The risk of retinal tear and detachment appears to be higher than in most conditions treated with vitrectomy.

Vitrectomy for the management of severe vitreous opacities is increasingly accepted because of the tremendous relief of symptoms reported by patients. The risks of retinal tear and detachment remain a concern, particularly in patients who have an attached posterior hyaloid. Yttrium-aluminum-garnet laser treatment of floaters may offer benefit in a subset of patients but appears to be less definitive than vitrectomy, and also may carry significant risk.
Update on maculopathy secondary to pentosan polysulfate toxicity
Authors: Abou-Jaoude Michelle , Fraser Claire , Maldonado Ramiro S.
Published: March 2021

Purpose of review

The aim of the present review is to provide a comprehensive summary of available knowledge regarding toxic maculopathy secondary to pentosan polysulfate sodium (PPS).

Recent findings

PPS toxicity was described in 2018, and additional studies characterize it as dysfunction of the retinal pigment epithelium centered on the posterior pole, which can progress despite drug cessation. Requisite exposure can be as little as 0.325 kg and 2.25 years but averages closer to 1–2 kg and 10–15 years. Multimodal imaging should include near-infrared reflectance, optical coherence tomography, and fundus autofluorescence. Cross-sectional studies demonstrate evidence correlating cumulative dosing and the likelihood/severity of maculopathy. Early estimates of prevalence range from 12.7 to 41.7% depending on dosing, with overall rates around 20%.

Reasonable evidence associates maculopathy with extended exposure to PPS, with an average reported incidence of around 20% in patients with long-term exposures. Patients with unexplained retinal pigment epithelium changes and difficulty with dark adaptation should be questioned regarding PPS exposure, and patients with known exposure to PPS should be examined. Further research is needed to refine screening protocols. Currently, providers should consider baseline examination and examination at 5 years and/or 500 g of exposure followed by yearly screening.
Language and Audiological Outcomes Among Infants Implanted Before 9 and 12 Months of Age Versus Older Children: A Continuum of Benefit Associated With Cochlear Implantation at Successively Younger Ages
Authors: Chweya Cynthia M. , May Matthew M. , DeJong Melissa D. , Baas Becky S. , Lohse Christine M. , Driscoll Colin L. W. , Carlson Matthew L.
Published: March 2021

Objective:

To compare language and audiological outcomes among infants (<9 and <12 mo) and older children receiving cochlear implantation (CI).

Study design:

Retrospective chart review.

Setting:

Tertiary academic referral center.

Patients:

Pediatric patients receiving CI between October 1995 and October 2019.

Intervention:

Cochlear implantation

Main Outcome Measures:

Most recent language and audiological assessment scores were evaluated by age group.

Results:

A total of 118 children were studied, including 19 who were implanted <9 months of age, 19 implanted 9 to <12 months of age, and 80 implanted 12 to <36 months of age. The mean duration of follow-up was 7.4 ± 5.0 years. Most recent REEL-3 receptive (88 ± 12 vs. 73 ± 15; p = 0.020) and expressive (95 ± 13 vs. 79 ± 12; p = 0.013) communication scores were significantly higher in the <9 months group compared to the 9 to <12 months group. PLS and OWLS auditory comprehension and oral expression scores were significantly higher in the <12 months group compared to the 12 to <36 months group. The difference in NU-CHIPS scores between <12 and 12 to <36 months was statistically significant (89% ± 6 vs. 83% ± 12; p = 0.009). LNT scores differed significantly between <9 and 9 to <12 months (94% ± 4 vs. 86% ± 10; p = 0.028).

Conclusions:

The recent FDA expansion of pediatric CI eligibility criteria to include infants as young as 9 months of age should not serve as a strict clinical cutoff. Rather, CI can be pursued in appropriately selected younger infants to optimize language and audiological outcomes.
High Prevalence of MYO6 Variants in an Austrian Patient Cohort With Autosomal Dominant Hereditary Hearing Loss
Authors: Frohne Alexandra , Koenighofer Martin , Liu David Tianxiang , Laccone Franco , Neesen Juergen , Gstoettner Wolfgang , Schoefer Christian , Lucas Trevor , Frei Klemens , Parzefall Thomas
Published: March 2021

Introduction:

Genetic hearing loss (HL) is often monogenic. Whereas more than half of autosomal recessive (AR) cases in Austria are caused by mutations in a single gene, no disproportionately frequent contributing genetic factor has been identified in cases of autosomal dominant (AD) HL. The genetic characterization of HL continues to improve diagnosis, genetic counseling, and lays a foundation for the development of personalized medicine approaches.

Methods:

Diagnostic HL panel screening was performed in an Austrian multiplex family with AD HL, and segregation was tested with polymerase chain reaction and Sanger sequencing. In an independent approach, 18 unrelated patients with AD HL were screened for causative variants in all known HL genes to date and segregation was tested if additional family members were available. The pathogenicity of novel variants was assessed based on previous literature and bioinformatic tools such as prediction software and protein modeling.

Results:

In six of the 19 families under study, candidate pathogenic variants were identified in MYO6, including three novel variants (p.Gln441Pro, p.Ser612Tyr, and p.Gln650ValfsTer7). Some patients carried more than one likely pathogenic variant in known deafness genes.

Conclusion:

These results suggest a potential high prevalence of MYO6 variants in Austrian cases of AD HL. The presence of multiple rare HL variants in some patients highlights the relevance of considering multiple-hit diagnoses for genetic counseling and targeted therapy design.
Hearing Outcomes After Surgical Manipulation of the Membranous Labyrinth During Superior Semicircular Canal Dehiscence Plugging or Posterior Semicircular Canal Occlusion
Authors: Lin Kenny F. , Bojrab Dennis I. , Fritz Christian G. , Vandieren Anthony , Babu Seilesh C.
Published: March 2021

Objective:

To analyze audiometric data after surgical manipulation of the membranous labyrinth during plugging of superior semicircular canal dehiscence (SSCD) or posterior semicircular canal occlusion (PSCO) for benign paroxysmal positional vertigo.

Study Design:

Retrospective chart review.

Setting:

Tertiary referral center.

Patients:

Patients undergoing plugging of SSCD or PSCO between 2009 and 2019.

Main Outcome Measures:

Pre- and postoperative audiometric data were collected per AAO-HNS guidelines. Hearing outcomes at initial and last follow-up were compared. Subanalyses were performed for surgical approach and age.

Results:

Eighty-seven total procedures in 76 patients including 43 middle cranial fossa for SSCD, 29 transmastoid SSCD, and 15 PSCO. Mean preoperative air-conduction–pure-tone averages was 21.1±14.9 dB compared with 26.1 ± 19.6 dB at initial follow-up and 24.4 ± 18.6 dB at last follow-up (p = 0.006). Mean preoperative bone-conduction–pure-tone average was 14.3 ± 11.9 dB compared with 18.3 ± 15.6 dB at initial follow-up and 18.5 ± 16.9 dB at last follow-up (p < 0.001). There were five cases of hearing loss >20 dB including one case of profound sensorineural hearing loss >55 dB. PSCO resulted in the most hearing loss at initial follow-up but largely resolves with time. Transmastoid approaches for SSCD resulted in more hearing loss compared with middle cranial fossa. Hearing outcomes were generally stable for SSCD approaches but showed improvement over time for PSCO. Age >50 was associated with greater hearing loss of 5.2 ± 11.1 dB compared with 1.3 ± 10.5 dB but did not reach statistical significance (p = 0.110).

Conclusions:

Surgical manipulation of the membranous labyrinth results in statistically significant hearing loss in a pooled analysis. Transient hearing loss is observed in PSCO and TM SSCD plugging was associated with postoperative hearing loss. There was a trend toward increased hearing loss in patients >50 years old.
Cochlear Implantation in NF2 Patients Without Intracochlear Schwannoma Removal
Authors: Eitutis Susan T. , Jansen Thijs , Borsetto Daniele , Scoffings Daniel J. , Tam Yu Chuen , Panova Tsvetemira , Tysome James R , Donnelly Neil P. , Axon Patrick R. , Bance Manohar L.
Published: March 2021

Objective:

To determine if cochlear implantation without removal of inner ear schwannomas (IES) is an effective treatment option for Neurofibromatosis 2 (NF2) patients. To determine how the presence of an intracochlear schwannoma might impact cochlear implant (CI) outcomes and programming parameters.

Study Design:

Retrospective chart review.

Setting:

Tertiary center for cochlear and auditory brainstem implantation.

Patients:

Of 10 NF2 patients with IES, 8 are reported with no previous tumor removal on the implanted ear.

Interventions:

Cochlear implant without tumor removal.

Main Outcome Measures:

Performance outcomes with CI at least 1-year post intervention. Programming parameters, including impedances, for patients with IES.

Results:

All patients had full insertion of the electrode arrays with round window approaches. Performance outcomes ranged from 0 to 100% for Bamford-Kowal-Bench sentences. Impedance measurements for active electrodes for patients with IES were comparable to those measured in patients without vestibular schwannoma (VS). Only patients who had radiation treatment before receiving their implant had elevated threshold requirements for CI programming compared with CI recipients without VS.

Conclusion:

Cochlear implantation without tumor removal is an effective option for treating NF2 patients with IES. The presence of an intracochlear tumor did not have an impact on CI performance or programming requirements compared with patients without VS; however, previous treatment with radiation may be related to elevated current requirements in the CI settings.
Clinical Performance Assessment of a New Active Osseointegrated Implant System in Mixed Hearing Loss: Results From a Prospective Clinical Investigation
Authors: Pla-Gil Ignacio , Redó María Aragonés , Pérez-Carbonell Tomàs , Martínez-Beneyto Paz , Alborch Miguel Orts , Ventura Antonio Morant , Monteagudo Emilia Latorre , Ribas Ignacia Pitarch , Algarra Jaime Marco
Published: March 2021

Objective:

Evaluation of a new active osseointegrated bone-conduction hearing implant in moderate to severe mixed-hearing loss.

Study Design:

Prospective observational study of a series of cases.

Setting:

Tertial referral center.

Patients:

Twenty patients with moderate mixed-hearing loss were evaluated (10 Cochlear Osia group and 10 Baha 5 Power Connect -control group).

Intervention:

Rehabilitative.

Main Outcome Measures:

Hearing performance in quiet and in noise and quality-of-life were evaluated.

Results:

Improvements in audibility, speech-understanding, speech-recognition, and quality-of-sound in noise and quiet were found for the Osia System compared with preoperative unaided hearing and performance was similar to that obtained with Baha 5 Power Connect.

Conclusions:

The new active transcutaneous bone conduction system provided a tonal improvement in free-field at middle and high frequencies. The performance in speech recognition in quiet and in noise was similar to control group outcomes.
Hearing Outcomes of Stapes Surgery in Children With Stapes Fixation and Ossicular Anomalies
Authors: Kang Byung Chul , Ku Ja Yoon , Ahn Joong Ho , Park Hong Ju , Chung Jong Woo
Published: March 2021

Objectives:

To investigate hearing outcomes after stapes surgery in children with stapes fixation.

Study Design:

Retrospective study.

Setting:

Tertiary referral center.

Patients:

Forty-nine patients (66 ears) aged less than 15 years who received stapes surgery.

Interventions:

Stapes surgery.

Main Outcomes and Measures:

Preoperative symptoms, bilateral involvement, pure-tone hearing levels, and perioperative complications were analyzed using paired t test and Mann–Whitney U test.

Results:

The chief complaint of all patients was hearing disturbance. Sixteen ears were diagnosed with stapes fixation and an additional congenital ossicular anomaly and 50 ears had only stapes fixation. Preoperative mean bone conduction and air conduction thresholds were 12.0 ± 5.8 dB and 60.9 ± 10.9 dB, respectively. The mean air-bone gap (ABG) was 48.9 ± 12.0 dB in patients with stapes fixation and an ossicular anomaly. The postoperative mean ABG was 23.6 ± 14.5 dB, and the ABG closure was 25.3 ± 18.2 dB. In patients with stapes fixation only, the preoperative mean bone conduction and air conduction thresholds were 14.3 ± 7.5 dB and 49.6 ± 9.5 dB, respectively, and the mean ABG was 35.5 ± 9.6 dB. The postoperative mean ABG was 14.4 ± 10.3 dB, and the ABG closure was 16.2 ± 16.1 dB. The successful results (ABG <20 dB) were 75.8% overall, 56.3% for fixation and an ossicular anomaly, and 82.0% for fixation only.

Conclusions:

In children with stapes fixation, hearing loss was worse when the fixation was combined with an ossicular anomaly. Ossicular continuity, especially of the incus, is the most important factor for successful stapes surgery. Appropriate diagnosis and surgical intervention can lead to good results for children with stapes fixation.
Renal metastases from esophageal cancer and retroperitoneal lymphoma detected via chromosome duplications identified by fluorescence in situ hybridization in urine exfoliated cells
Authors: Hu Zhiquan , Ke Chunjin , Shen Yuanqing , Zeng Xing , Yang Chunguang
Published: March 2021

Rationale:

Renal-occupying lesions positive for urine fluorescence in situ hybridization (FISH) are usually considered urothelial carcinomas. Here, we describe 2 cases of renal metastases with chromosome duplications in urine exfoliated cells.

Patient symptoms:

Patient 1, a 56-year-old male with a history of esophageal cancer, was admitted to our hospital on May 2017 after presenting with right back pain with microscopic hematuria for 1 month. Magnetic resonance imaging (MRI) showed right renal space-occupying lesions (5.4 cm × 4.6 cm) and multiple enlarged lymph nodes in the right renal hilum and retroperitoneum. The cystoscopy results were negative, and FISH analysis of urine exfoliated cells was positive, indicative of chromosome 3, 7, and 17 amplifications. Patient 2 was a 50-year-old male who was admitted to our hospital on May 2019 with no obvious cause of abdominal pain and abdominal distension (lasting for 7 days), with a serum creatinine level of 844 μmol/L. Patient 2 had no hematuria or fever, and MRI showed left renal inferior and medial space-occupying lesions, and multiple mesenteric nodules at the junction of the left adrenal gland, retroperitoneum, abdomen, and pelvis, which were partially fused. The tumor lesions were approximately 3.1 cm × 2.3 cm in size. The urine FISH results were positive, indicating chromosome 3, 7, and 17 amplifications.

Diagnoses:

Both patients were diagnosed with renal tumors with unknown pathology.

Interventions:

Patient 1 underwent laparoscopic resection of the kidney and ureter, and sleeve cystectomy. The postoperative pathological diagnosis was metastatic keratinized squamous cell carcinoma, with squamous cell carcinoma in the right hilar lymph node. Histological FISH of the primary esophageal cancer and renal metastases were consistent with the urine FISH test results. Patient 2 underwent a biopsy of the left renal inferior and retroperitoneal areas, and was diagnosed with diffuse large B-cell lymphoma.

Outcomes:

Patient 1 survived 6 months after urological surgery. After treating patient 2 with the R-CHOP regimen and kinase inhibitors, his renal function recovered significantly and the mass become undetectable.

Lessons:

Our results imply that FISH-positive renal occupying lesions should be considered as potential renal metastases with chromosome aberrations when making a differential diagnosis.
Effect of clinician's experience and expertise on the inter- and intra-observer reliability of hip migration index in children with cerebral palsy
Authors: Demir Necdet , Demirel Mehmet , Turna Önder , Yildizlar Derya , Demirbaş Önder , Sağlam Yavuz
Published: March 2021

Few studies have investigated the reliability of Reimers’ hip migration percentage (RMP) in children with cerebral palsy (CP). Most studies on the topic reflected rating results of physician with a similar level of experience from the same expertise. This study aimed to determine the effect of clinician's experience and expertise on the intra-and inter-observer reliability of RMP.

In this retrospective observational study, hip radiographs of children with CP were identified. 5 observers with different degrees of working experience from 3 different clinical fields, including orthopedics, radiology, and physical medicine and rehabilitation, performed all RMP measurements. All measurements were repeated 6 weeks later by the same observers. Inter- and intra-observer reliability for RMP measurements were assessed using Intraclass Correlation Coeficient (ICC), calculated from 2 sets of repeated measurements on a subset of 50 hips, with a 6 week apart for each observer.

Fifty hip radiographs of 25 children with CP (10 females and 15 males; mean age: 6 years; age range: 2–8 years) were examined in the current study. No significant differences existed in intra-and inter-observer measurements. Excellent intra-observer reliability was observed between the 2 separate measurements for each observer, with a mean ICC of 0.976 (range: 0.956–0.989; P < .001). Among 5 observers, inter-observer reliability was excellent for the 2 separate RMP measurements, with the mean ICC minimally increasing between the 2 measurement periods (mean ICC: 0.928, range: 0.838–0.979 and mean ICC: 0.936, range: 0.861–0.983, respectively) (P < .001).

Clinician's experience and expertise may not affect inter-and intra-observer reliability of RMP measurements.
Development and validation of a robust immune-related risk signature for hepatocellular carcinoma
Authors: Liu Zaoqu , Jiao Dechao , Liu Long , Zhou Xueliang , Yao Yuan , Li Zhaonan , Li Jing , Chen Jianjian , Lei Qinyu , Han Xinwei
Published: March 2021

Background:

Increasing evidence has indicated immune-related genes (IRGs) play a key role in the development of hepatocellular carcinoma (HCC). Whereas, there have been no investigations proposing a reliable prognostic signature in terms of IRGs. This study aimed to develop a robust signature based on IRGs in HCC. A total of 597 HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were enrolled in this study.

Methods:

The TCGA cohort was utilized for discovery, and the ICGC cohort was utilized for validation. Multiple algorithms were implemented to identify key prognostic IRGs and establish an immune-related risk signature. Bioinformatics analysis and R soft tools were utilized to annotate underlying biological functions.

Results:

A total of 1416 differentially expressed mRNAs (DEMs) were screened, of which 90 were differentially expressed IRGs (DEIRGs). Using univariate Cox regression analysis, we identified 33 prognostically relevant DEIRGs. Using least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis, we extracted 8 optimal DEIRGs to construct a risk signature in the TCGA cohort, and the signature was verified in the ICGC cohort. We also built a nomogram to increase the accuracy of predicting HCC prognosis. By investigating the relationship of the risk score and 8 risk genes from our signature with clinical traits, we found that the aberrant expression of the immune-related risk genes is correlated with the development of HCC. Moreover, the high-risk group was higher than the low-risk group in terms of tumor mutation burden (TMB), immune cell infiltration, and the expression of immune checkpoints (programmed cell death protein 1 [PD-1], programmed cell death ligand 1 [PD-L1], and cytotoxic T-lymphocyte-related protein 4 [CTLA-4]), and functional enrichment analysis indicated the signature enriched an intensive immune phenotype.

Conclusion:

This study developed a robust immune-related risk signature and built a predictive nomogram that reliably predict overall survival in HCC, which may be helpful for clinical management and personalized immunotherapy decisions.
Pathogeny of cerebral venous thrombosis in SARS-Cov-2 infection
Authors: Guendouz Cécile , Quenardelle Véronique , Riou-Comte Nolwenn , Welfringer Pascal , Wolff Valérie , Zuily Stéphane , Jager Lavinia , Humbertjean Selton Lisa , Mione Gioia , Pop Raoul , Gory Benjamin , Richard Sébastien
Published: March 2021

Rationale:

Pathogeny of thrombosis in COVID-19 is related to interaction of SARS-Cov-2 with vascular wall through the angiotensin converting enzyme 2 (ACE2) receptor. This induces 2 pathways with immunothrombosis from activated endothelium (cytokine storm, leukocyte and platelet recruitment, and activation of coagulation extrinsic pathway), and rise of angiotensin II levels promoting inflammation. While thrombosis is widely described in COVID-19 patients admitted in intensive care unit, cerebrovascular diseases remains rare, in particular cerebral venous thrombosis (CVT).

Patient concerns:

We describe 2 cases of women admitted during the spring of 2020 for intracranial hypertension signs, in stroke units in Great-east, a French area particularly affected by COVID-19 pandemia.

Diagnoses:

Cerebral imaging revealed extended CVT in both cases. The first case described was more serious due to right supratentorial venous infarction with hemorrhagic transformation leading to herniation. Both patients presented typical pneumonia due to SARS-Cov-2 infection, confirmed by reverse transcription polymerase chain reaction on a nasopharyngeal swab in only one.

Interventions:

The first patient had to undergo decompressive craniectomy, and both patients were treated with anticoagulation therapy.

Outcomes:

Favorable outcome was observed for 1 patient. Persistent coma, due to bi thalamic infarction, remained for the other with more serious presentation.

Lessons:

CVT, as a serious complication of COVID-19, has to be searched in all patients with intracranial hypertension syndrome. Data about anticoagulation therapy to prevent such serious thrombosis in SARS-Cov-2 infection are lacking, in particular in patients with mild and moderate COVID-19.