bluuebunny/crossref_metadata_2025 huggingface dataset:
OCULAR SURFACE TEMPERATURE DIFFERENCES IN RETINAL VASCULAR DISEASES
Authors: Naidorf-Rosenblatt Hadar , Landau-Part Daphna , Moisseiev Joseph , Alhalel Amir , Huna-Baron Ruth , Skaat Alon , Pilus Sima , Levi Lior , Leshno Ari
Published: August 2021

Purpose:

To define the effect of age-related macular degeneration (AMD) and diabetic retinopathy (DR) on the ocular thermographic profile.

Methods:

This retrospective cross-sectional study included subjects diagnosed with DR or AMD between January and April 2019. Individuals without ocular disease served as controls. A thermal imaging camera was used for ocular surface temperature (OST) acquisition. The mean temperatures of the medial cantus, lateral cantus, and cornea were calculated.

Results:

Thermographic images were obtained from 133 subjects (260 eyes, 97 DR and 163 AMD) and 48 controls (55 eyes). Ocular surface temperature was higher among patients with AMD and lowest among patients with DR (P < 0.001). A subgroup analysis revealed that eyes with diabetic macular edema had significantly higher OSTs than DR eyes without diabetic macular edema. Moreover, the OST in eyes with diabetic macular edema was similar to the measurements of the AMD group. There were no differences in OSTs between neovascular and nonneovascular AMD eyes.

Conclusion:

Although AMD and DR are considered posterior segment conditions, their effect on OST implies that the entire globe is involved. Although both conditions result from similar multifactorial pathophysiologic changes, the differences in OST between DR and AMD might be due to dissimilarity in the balance of pathologic processes involved in each condition. Further research is required to better understand the pathophysiology of these diseases and their effect on OST as well as to determine the effect of vasculature, circulation, and tissue metabolism on ocular temperature.
Outcomes of Microbial Keratitis Cases Resistant to Antimicrobials in Sydney, Australia
Authors: Cabrera-Aguas Maria , Khoo Pauline , Watson Stephanie L.
Published: August 2021

Purpose:

The purpose of this study was to describe demographics, predisposing factors, clinical features, treatment, and outcomes of microbial keratitis cases resistant to antimicrobials.

Methods:

A retrospective case series was conducted. All patients with microbial keratitis resistant to antimicrobials who underwent a corneal scrape and culture from 2012 to December 2016 at the Sydney Eye Hospital were included. Cases were identified from pathology and hospital coding data. Coagulase-negative staphylococci (CoNS), Staphylococcus aureus (S. aureus), and Corynebacterium spp. resistant to cefalotin, chloramphenicol, ciprofloxacin, or gentamicin were analyzed.

Results:

One hundred fifteen episodes had a resistant CoNS, 24 S. aureus, and 12 Corynebacterium spp. Antimicrobial resistance was associated with older women (67%, median age 83 years) with Corynebacterium spp. (P < 0.001), corneal graft, and previous topical steroid use. Larger epithelial defects (P = 0.203) and infiltrates (P = 0.180) were more likely to be associated with Corynebacterium spp., but not statistically significant. At the initial and final visits, resistant S. aureus (75% vs. 67%) and Corynebacterium spp. (78% vs. 80%) cases were more likely to be classified as blind (>3/60) compared with CoNS (45% vs. 28%) (P = 0.011 vs. P = 0.004). Corneal perforation occurred more often in resistant S. aureus cases (P < 0.001), whereas slow and nonhealing epithelial defects needing other procedures were more likely to occur with resistant Corynebacterium spp. (P < 0.001).

Conclusions:

Patients with resistant CoNS were younger and presented with smaller ulcers and moderate vision loss. Visual and clinical outcomes were significantly better for resistant CoNS than for those with resistant S. aureus or Corynebacterium spp.
Confirmation of PRDX3 c.568G>C as the Genetic Basis of Punctiform and Polychromatic Pre-Descemet Corneal Dystrophy
Authors: Choo Charlene H. , Boto de los Bueis Ana , Chung Doug D. , Aldave Anthony J.
Published: August 2021

Purpose:

The aim of this study was to report the results of screening peroxiredoxin 3 (PRDX3) and PDZ domain-containing protein 8 (PDZD8) in a previously unreported pedigree with punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) to confirm that the PRDX3 mutation c.568G>C is the genetic basis of PPPCD.

Methods:

Ophthalmologic examination of the proband and her affected father was performed with slit lamp biomicroscopy. Saliva was collected from the proband as a source of DNA, after which screening for PRDX3 and PDZD8 was performed.

Results:

Slit lamp examination of the proband revealed polychromatic deposits diffusely distributed at the pre-Descemet level in both corneas and anterior subcapsular in the crystalline lens of both eyes. The proband's father also demonstrated diffuse pre-Descemetic polychromatic deposits in both eyes but no lenticular deposits. Screening of PRDX3 in the proband demonstrated the c.568G>C (p.Asp190His) variant previously associated with PPPCD and failed to identify any variants in PDZD8.

Conclusions:

We report the initial confirmation of PRDX3 as the genetic basis of PPPCD in a previously unreported pedigree and expand the phenotype of PPPCD to include polychromatic lenticular deposits.
The impact of COVID-19 in pregnancy: Part I. Clinical presentations and untoward outcomes of pregnant women with COVID-19
Authors: Wang Peng-Hui , Lee Wen-Ling , Yang Szu-Ting , Tsui Kuan-Hao , Chang Cheng-Chang , Lee Fa-Kung
Published: August 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019, COVID-19) is a pandemic disease with rapidly and widely disseminating to the world. Based on experiences about the H1N1, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) coronavirus pandemics, pregnant women who are infected are disproportionately more likely to develop severe illness and need more hospitalizations, intensive care, and finally die of diseases compared with those nonpregnant counterparts or those pregnant women without infection. Although more than one half of pregnant women with COVID-19 are asymptomatic, and as well as their symptoms are frequently mild, this observation presents a further challenge regarding service provision, prevention, and management, in which this may result in overlooking the risk of COVID-19 during pregnancy. As predictable, despite much advance in critical care in recent decades, during the 2020 COVID-19 pandemic, pregnant women with COVID-19 are really at higher risk to progress to severe illness; require hospitalization; need intensive care, such as the use of mechanical ventilation as well as extracorporeal membrane oxygenation (ECMO), and of most important, die than their nonpregnant counterparts and pregnant women without COVID-19. The magnitude of the risk to pregnant women further extend to their newborn from COVID-19 with resultant significantly increasing perinatal and neonatal morbidity and mortality rates. The heightened risk of untoward outcomes in pregnant women emphasizes an urgent need of national or international recommendations and guidelines to optimize prevention and management strategies for COVID-19 in pregnancy. Active and passive prevention of COVID-19 is approved as effective strategies for women who attempt to be pregnant or during pregnancy. Understanding that pregnant women who are a vulnerable population is essential to improve the care in the novel and urgent COVID-19 pandemic. The current review is a part I to summarize the up-to-date information about the impact of laboratory-confirmed SARS-CoV-2 infection on pregnant women and focus on clinical presentations and untoward pregnancy outcomes of these pregnant women infected with SARS-CoV-2.
Post-COVID Care Center to Address Rehabilitation Needs in COVID-19 Survivors: A Model of Care
Authors: Ahmad Maleeha , Kim Kangmin , Indorato Daniel , Petrenko Irina , Diaz Keith , Rotatori Francesco , Salhany Richard , Lakhi Nisha
Published: August 2021

The severe acute respiratory syndrome coronavirus 2019 pandemic surge left a large cohort of patients vulnerable to cardiopulmonary, neurological, and psychiatric complications. This post-COVID Care center was established to identify patients with disease sequalae and deliver early multidisciplinary rehabilitation services. The evaluation included comprehensive history and physicals, screening tests, labs, and imaging to determine appropriate specialist referrals. After a 6-month period, 278 unique referrals were made to address symptoms reported by 114 patients in specialities including pulmonology, cardiology, and psychiatry. This framework allowed for individualized patient treatment and monitoring of disease after the acute phase of infection. This study highlights the substantial physical and psychosocial impact a coronavirus disease 2019 infection has on patients’ long-term trajectory and emphasizes the need for early targeted rehabilitation Post-COVID Care centers. As the world transitions into the chronic phase of this pandemic, this model of care will provide a framework to improve the quality of health care delivery.
The Association Between Clearance of Human Papillomavirus After Conization for Cervical Cancer and Absence of Cancer
Authors: Siegler Efraim , Goldberg Yael , Siegler Yoav , Shaked-Mishan Pninit , Mazareb Salam , Kugelman Nir , Mackuli Lena , Sabo Edmond , Lavie Ofer , Segev Yakir
Published: August 2021

Objectives

We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS).

Materials Methods

Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3–12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ.

Results

The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV–negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p < .006).

In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p < .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%.

Conclusions

Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.
Digital Live Imaging of Intraoperative Electrocochleography – First Description of Feasibility and Hearing Preservation During Cochlear Implantation
Authors: Arweiler-Harbeck Diana , D’heygere Victoria , Meyer Moritz , Hans Stefan , Waschkies Laura , Lang Stephan , Anton Kristina , Hessel Horst , Schneider Armin , Heiler Thomas , Höing Benedikt
Published: August 2021

Introduction:

Intraoperative electrocochleography (ECochG) during cochlear implantation is a promising tool to preserve residual hearing. However, the time gap between insertion of the electrode and acoustic feedback from the audiologist to the surgeon can cause delay and subsequently irreparable damage to cochlear structures. In this feasibility study, for the first time, real-time visualization of intraoperative ECochG via digital microscope display directly to the surgeon was successfully performed in four patients.

Materials and methods:

Four patients with residual hearing underwent cochlear implantation. Intraoperative electrocochleography responses were collected and direct visualization during the time of electrode insertion into the surgeon's field of view in the binoculars using augmented real-time digital imaging was realized. The time of electrode insertion was recorded. Hearing preservation was determined by testing postoperative changes in behavioral thresholds.

Results:

Digital live visualization of intraoperative ECochG using image augmentation in a digital microscope was successfully performed in all cases and enabled direct adaptation of the surgeon's insertion behavior. Mean time of electrode insertion was 129.8 seconds. Postoperative behavioral thresholds were comparable to preoperative taken thresholds. Preservation of residual hearing in the low frequency range was possible.

Discussion:

This study is the first to describe digital visualization of intraoperative electrocochleography as a new method enabling the surgeon to directly react to changes in amplitude of the cochlea microphonics. Our results show that augmentation of the intraoperative live imaging with electrical potentials could add to hearing preservation during cochlear implantation.
Impact of Mental Health Insurance Legislation on Mental Health Treatment in a Longitudinal Sample of Adolescents
Authors: Heboyan Vahé , Douglas Megan D. , McGregor Brian , Benevides Teal W.
Published: August 2021

Background:

Mental health insurance laws are intended to improve access to needed treatments and prevent discrimination in coverage for mental health conditions and other medical conditions.

Objectives:

The aim was to estimate the impact of these policies on mental health treatment utilization in a nationally representative longitudinal sample of youth followed through adulthood.

Methods:

We used data from the 1997 National Longitudinal Survey of Youth and the Mental Health Insurance Laws data set. We specified a zero-inflated negative binomial regression model to estimate the relationship between mental health treatment utilization and law exposure while controlling for other explanatory variables.

Results:

We found that the number of mental health treatment visits declined as cumulative exposure to mental health insurance legislation increased; a 10 unit (or 10.3%) increase in the law exposure strength resulted in a 4% decline in the number of mental health visits. We also found that state mental health insurance laws are associated with reducing mental health treatments and disparities within at-risk subgroups.

Conclusions:

Prolonged exposure to comprehensive mental health laws across a person’s childhood and adolescence may reduce the demand for mental health visitations in adulthood, hence, reducing the burden on the payors and consumers. Further, as the exposure to the mental health law strengthened, the gap between at-risk subgroups was narrowed or eliminated at the highest policy exposure levels.
Comparison of Incremental Vestibulo-ocular Reflex Adaptation Training Versus x1 Training in Patients With Chronic Peripheral Vestibular Hypofunction: A Two-Year Randomized Controlled Trial
Authors: Rinaudo Carlo N. , Schubert Michael C. , Cremer Phillip D. , Figtree William V. C. , Todd Christopher J. , Migliaccio Americo A.
Published: August 2021

Background and Purpose:

A crossover, double-blinded randomized controlled trial to investigate once-daily incremental vestibulo-ocular reflex (VOR) adaptation (IVA) training over 2 years in people with stable and chronic peripheral vestibular hypofunction.

Methods:

Twenty-one patients with peripheral vestibular hypofunction were randomly assigned to intervention-then-control (n = 12) or control-then-intervention (n = 9) groups. The task consisted of either x1 (control) or IVA training, once daily every day for 15 minutes over 6-months, followed by a 6-month washout, then repeated for arm 2 of the crossover. Primary outcome: vestibulo-ocular reflex gain. Secondary outcomes: compensatory saccades, dynamic visual acuity, static balance, gait, and subjective symptoms. Multiple imputation was used for missing data. Between-group differences were analyzed using a linear mixed model with repeated measures.

Results:

On average patients trained once daily 4 days per week. IVA training resulted in significantly larger VOR gain increase (active: 20.6% ± 12.08%, P = 0.006; passive: 30.6% ± 25.45%, P = 0.016) compared with x1 training (active: −2.4% ± 12.88%, P = 0.99; passive: −0.6% ± 15.31%, P = 0.68) (P < 0.001). The increased IVA gain did not significantly reduce with approximately 27% persisting over the washout period. x1 training resulted in greater reduction of compensatory saccade latency (P = 0.04) and increase in amplitude (P = 0.02) compared with IVA training. There was no difference between groups in gait and balance measures; however, only the IVA group had improved total Dizziness Handicap Inventory (P = 0.006).

Discussion and Conclusions:

Our results suggest IVA improves VOR gain and reduces perception of disability more than conventional x1 training. We suggest at least 4 weeks of once-daily 4 days-per-week IVA training should be part of a comprehensive vestibular rehabilitation program.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A356).
Is there a correlation between functional results and radiographic findings in patients with distal radius fracture A0 type A3 treated with volar locking plate or external fixator?
Authors: Ludvigsen Trine , Matre Kjell , Vetti Nils , Kristoffersen Per Martin , Toppe Monika Kolskår , Gudmundsdottir Rakel , Krukhaug Yngvar , Dybvik Eva , Fevang Jonas Meling
Published: August 2021

Purpose:

The aim of this study was to test the hypothesis that precise restoration of distal radius fractures is correlated to better patient-reported outcome.

Methods:

The correlation between radiographic results and functional outcome was explored in 156 patients with extra-articular distal radius fractures included in a multicenter, randomized controlled trial comparing 2 surgical interventions, Volar Locking Plate or External Fixator. The primary functional outcome was the Patient Rated Wrist and Hand Evaluation score (PRWHE). Radiographically we assessed volar tilt, radial inclination, radial height, ulnar variance, and the presence of ulnar styloid fracture. The Pearson correlation analysis was used to estimate correlations between parameters.

Results:

At 1-year follow-up the mean difference in radiographic findings compared with the uninjured side (min, max) was: reduced volar tilt 5.3° (−15°, 25°), reduced radial inclination 2.3° (−6°, 12°), radial height 1.3 mm (−4 mm, 7 mm), and ulnar variance −0.5 mm (−6 mm, 3 mm). Overall, we found no correlation between radiographic parameters and the PRWHE at 1-year follow-up within the whole group, regardless of which treatment was chosen. At the time of injury 53% (N = 80) had sustained an additional ulnar styloid fracture. After 1 year this fracture was still radiographically present in 31% (N = 43) of the patients. No correlation between PRWHE score and the presence of an ulnar styloid fracture at 1-year follow-up was found.

Conclusions:

We found no correlation between functional outcome (PRWHE) and radiographic findings after 1 year in patients operated on with a Volar Locking Plate or External Fixator. Patient-specific factors were more important than radiographic measurements in this study group.

Level of evidence: Therapeutic Level 2

Trial registration: Norway: National Committee for Medical and Health Research Ethics 213/555

ClinicalTrials.gov ID: NCT01904084

Randomization of first patient: 02.09.2013
Spread Through Air Spaces (STAS) in Non−Small Cell Lung Carcinoma
Authors: Gross Daniel J. , Hsieh Min-Shu , Li Yan , Dux Joseph , Rekhtman Natasha , Jones David R. , Travis William D. , Adusumilli Prasad S.
Published: August 2021

Tumor spread through air spaces (STAS) is associated with locoregional recurrence in patients undergoing limited resection (LR) for non−small cell lung carcinoma (NSCLC). We hypothesized that the observation of STAS in both the initial LR specimen and the additional resection specimen from the same patient, processed using different knives, would provide evidence that STAS is an in vivo phenomenon contributing to locoregional recurrence. We retrospectively identified patients with NSCLC (9 adenocarcinoma, 1 squamous cell carcinoma) who underwent LR, had STAS in the LR specimen, and underwent additional resection (lobectomy or LR). The LR and additional resection specimens from each patient were processed at different times using different tissue-processing knives. All specimens were analyzed for STAS. All 10 patients underwent LR with negative margins (R0). All additional resection specimens had STAS: 8 patients had STAS clusters in their completion lobectomy specimens, and 2 had STAS in their additional LR specimens. In 2 patients, STAS was found in the completion lobectomy specimen only after extensive sampling (>10 sections) from the staple line adjacent to the initial LR. The presence of STAS in both the LR and the additional resection specimen processed using different knives supports the concept that STAS is an in vivo phenomenon, rather than an artifact from tissue processing. This observation indicates that occult STAS tumor cells can be present in the lung tissue of the remaining unresected lobe after LR and supports the concept that STAS is a contributing factor for locoregional recurrence following LR.
When Should We Perform Intraoperative Cholangiography? A Prospective Assessment of 1000 Consecutive Laparoscopic Cholecystectomies
Authors: Dreifuss Nicolás H. , Lendoire Mateo , McCormack Lucas , Capitanich Pablo , Iovaldi Mario L. , Schlottmann Francisco
Published: August 2021

Background:

Intraoperative cholangiography (IOC) has been historically used to detect common bile duct (CBD) stones, delineate biliary anatomy, and avoid or promptly diagnose bile duct injuries (BDIs) during laparoscopic cholecystectomy (LC). We aimed to determine the usefulness of routine IOC during LC in an urban teaching hospital.

Methods:

A consecutive series of patients undergoing LC with routine IOC from 2016 to 2018 was prospectively analyzed. Primary outcomes of interest were: CBD stones, BDI, and anatomical variations of the biliary tract. Secondary outcomes of interest were: IOC success rate, IOC time, and readmission for residual lithiasis. A comparative analysis was performed between patients with and without preoperative suspicion of CBD stones.

Results:

A total of 1003 LC were analyzed; IOC was successful in 918 (91.5%) patients. Mean IOC time was 10 (4 to 30) minutes. Mean radiation received by the surgeon per procedure was 0.06 millisieverts (mSv). Normal IOC was found in 856 (93.2%) patients. CBD stones and aberrant biliary anatomy were present in 58 (6.3%) and 4 (0.4%) cases, respectively. Two patients (0.2%) underwent unnecessary CBD exploration because of false-positive IOC. Four patients (0.4%) with normal IOC were readmitted for residual CBD stones. Five (0.5%) minor BDI undetected by the IOC were diagnosed. Patients with preoperative suspicion of CBD stones had significantly higher rates of CBD stones detected on IOC as compared with those without suspicion (23.2% vs. 2.1%, P<0.0001).

Conclusion:

Routine use of IOC resulted in low rates of BDI diagnosis, aberrant biliary anatomy identification and/or CBD stones detection. Selection of patients for IOC, rather than routine use of IOC appears a more reasonable approach.
Liver Transplant Center Size and the Impact on Clinical Outcomes and Resource Utilization
Authors: Alqahtani Saleh A. , Stepanova Maria , Kabbara Khaled W. , Younossi Issah , Mishra Alita , Younossi Zobair
Published: August 2021

Background.

Prior studies suggest that transplant center volume is associated with liver transplantation (LT) outcomes. We compared patient characteristics and waitlist outcomes among transplant centers in the United States with different volumes.

Methods.

Data for adult waitlisted candidates and LT recipients in the United States between 2008 and 2017 were extracted from the Scientific Registry of Transplant Recipients database. Transplant centers were categorized by transplants/year into tertiles: low-volume centers (LVCs; <20 transplantations/y); medium-volume centers (MVCs; 20–55 transplantations/y); and high-volume centers (HVCs; >55 transplantations/y). Patient characteristics, waitlist outcomes, and factors associated with posttransplantation mortality were compared.

Results.

From 141 centers, 112 110 patients were waitlisted for LT: 6% at LVCs, 26% at MVCs, and 68% at HVCs. Patients listed at LVCs were less likely to have private insurance but had higher Medicaid and Veterans Affairs healthcare rates. Patients at LVCs were less likely to receive LT (47% versus 53% in MVC versus 61% in HVC), had higher transfer rates to other centers, and were more likely to be removed from the waitlist. In competing risk survival analysis, adjusted for center location, MELD score, and clinicodemographic factors, patients listed at an HVC were more likely to receive LT (adjusted hazard ratio:1.30; 95% confidence interval = 1.27-1.33; P < 0.001). Among LT recipients (n = 62 131), receiving a transplant at an LVC was associated with higher post-LT mortality (adjusted hazard ratio: 1.16; 95% confidence interval = 1.05-1.28; P = 0.003).

Conclusions.

Patients at LVCs were less likely to receive a LT and had a higher risk of post-LT death.
Nitrogeniibacter mangrovi gen. nov., sp. nov., a novel anaerobic and aerobic denitrifying betaproteobacterium and reclassification of Azoarcus pumilus as Aromatoleum pumilum comb. nov.
Authors: Liao Hu , Qu Mingming , Hou Xinyue , Lin Xiaolan , Li Hu , Duan Chen-song , Tian Yun
Published: August 2021

Denitrification is a vital link in the global bio-nitrogen cycle. Here, we isolated a strain (M9-3-2T) that is a novel benzo[a]pyrene (BaP)-tolerant, anaerobic and aerobic denitrifying bacterium from a continuous BaP-enrichment cultured mangrove sediment. In silico comparative genomics and taxonomic analysis clearly revealed that strain M9-3-2T (=MCCC 1K03313T=JCM 32045T) represents a novel species of a novel genus named as Nitrogeniibacter mangrovi gen. nov., sp. nov., belonging to family

Zoogloeaceae

, order

Rhodocyclales

. In addition, the species

Azoarcus pumilus

is transferred into genus

Aromatoleum

and named Aromatoleum pumilum comb. nov. The predominant respiratory quinone of strain M9-3-2T was ubiquinone-8 and the major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, three unidentified phospholipids and three unidentified aminophospholipids. In this study, the capacity of strain M9-3-2T to eliminate nitrate was detected under anaerobic and aerobic conditions, and the removal rates of nitrate were 6.1×10−6 µg N/l/h/cell and 3×10−7 µg N/l/h/cell, respectively. Our results suggested that strain M9-3-2T could play an important role in the nitrogen removal regardless of the presence of oxygen in natural or/and man-made ecosystems.
Validation of saliva sampling as an alternative to oro-nasopharyngeal swab for detection of SARS-CoV-2 using unextracted rRT-PCR with the Allplex 2019-nCoV assay
Authors: Bergevin Marco Andres , Freppel Wesley , Robert Guylaine , Ambaraghassi Georges , Aubry Dany , Haeck Olivier , Saint-Jean Maude , Carignan Alex
Published: August 2021

Introduction. The current severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) pandemic has stressed the global supply chain for specialized equipment, including flocked swabs.

Hypothesis. Saliva could be a potential alternative specimen source for diagnosis of SARS-CoV-2 infection by reverse-transcriptase PCR (RT-PCR).

Aim. To compare the detection efficiency of SARS-CoV-2 RNA in saliva and oro-nasopharyngeal swab (ONPS) specimens.

Methodology. Patients recruited from hospital provided paired saliva and ONPS specimens. We performed manual or automated RT-PCR with prior proteinase K treatment without RNA extraction using the Seegene Allplex 2019 nCoV assay.

Results. Of the 773 specimen pairs, 165 (21.3 %) had at least one positive sample. Additionally, 138 specimens tested positive by both sampling methods. Fifteen and 12 cases were detected only by nasopharyngeal swab and saliva, respectively. The sensitivity of ONPS (153/165; 92.7 %; 95 % CI: 88.8–96.7) was similar to that of saliva (150/165; 90.9 %; 95 % CI: 86.5–95.3; P=0.5). In patients with symptoms for ≤ 10 days, the sensitivity of ONPS (118/126; 93.7 %; 95 % CI: 89.4–97.9) was similar to that of saliva (122/126; 96.8 %; 95 % CI: 93.8–99.9 %; P=0.9). However, the sensitivity of ONPS (20/22; 95.2 %; 95 % CI: 86.1–100) was higher than that of saliva (16/22; 71.4 %; 95 % CI: 52.1–90.8) in patients with symptoms for more than 10 days.

Conclusions. Saliva sampling is an acceptable alternative to ONPS for diagnosing SARS-CoV-2 infection in symptomatic individuals displaying symptoms for ≤ 10 days. These results reinforce the need to expand the use of saliva samples, which are self-collected and do not require swabs.
Modeling spatiotemporal Aedes aegypti risk in French Guiana using meteorological and remote sensing data
Authors: Bailly Sarah , Machault Vanessa , Beneteau Samuel , Palany Philippe , Girod Romain , Lacaux Jean-Pierre , Quenel Philippe , Flamand Claude
Published: August 2021

Although the development of vaccines for the prevention of arboviral diseases has been a priority in recent years, prevention strategies continue to depend on vector control. Risk maps at scales appropriate for these strategies can provide valuable information to assess entomological risk levels and guide actions. We used a spatio-temporal modeling approach to predict, at the local scale, the risk of homes potentially harboring Aedes aegypti larvae. The model used integrated larvae risk data collected in the field from September 2011 to February 2013, environmental data obtained from very high spatial resolution Pleiades imagery, and daily meteorological data, collected in the city of Matoury in French Guiana. Various environmental and meteorological conditions were identified as risk or protective factors for the presence of immature stages of Aedes aegypti in homes on a given date and used to produce dynamic maps with high spatial and temporal resolution. Aedes vector risk was modeled between 50 and 200 m, around houses, on a time scale of 3 to 5 days. The resulting model was extrapolated to other municipalities with the same characteristics of urbanization during the 2019-2020 dengue epidemic in French Guiana. This work represents a major opportunity to monitor the evolution of vector risk and constitutes information that could be particularly useful for public health authorities in charge of vector control.
Green spaces, especially forest, linked to lower SARS-CoV-2 infection rates: A one-year nationwide study
Authors: Jiang Bin , Yang Yuwen , Chen Long , Liu Xueming , Wu Xueying , Chen Bin , Webster Chris , Sullivan William C. , Wang JingJing , Lu Yi
Published: August 2021

This study examined the associations between green spaces and one-years’ worth of SARS-CoV- 2 infection rates across all 3,108 counties in the contiguous United States after controlling for multiple categories of confounding factors. We found green spaces at the county level have a significant negative association with infection rates. Among all types of green spaces, forest yields the most consistent and strongest negative association. Sensitivity analyses confirmed the negative association of forest across five urbanicity levels, and the strength of the association increases as disease incidence increases across five time periods. Although forest located in moderately urbanized counties yields the strongest association, the negative pattern of significant associations holds across all five urbanicity levels. A population-weighted analysis revealed that proximity to forest within a moderate walking distance (≤ 1.0–1.4 km) may provide the greatest protection against the risk of infection.
Durability and Cross-Reactivity of Immune Responses Induced by an AS03-Adjuvanted Plant-Based Recombinant Virus-Like Particle Vaccine for COVID-19
Authors: Gobeil Philipe , Pillet Stéphane , Boulay Iohann , Charland Nathalie , Lorin Aurélien , Cheng Matthew P. , Vinh Donald C. , Boutet Philippe , Van Der Most Robbert , Roman François , Angeles Ceregido Maria , Landry Nathalie , D’Aoust Marc-André , Ward Brian J.
Published: August 2021

As the SARS-COV-2 pandemic evolves, what is expected of vaccines extends beyond efficacy to include consideration of both durability and variant cross-reactivity. This report expands on previously reported immunogenicity results from a Phase 1 trial of an AS03-adjuvanted, plant-based coronavirus-like particle (CoVLP) displaying the spike (S) glycoprotein of the ancestral SARS-CoV-2 virus in healthy adults 18-49 years of age (NCT04450004). When humoral and cellular responses against the ancestral strain were evaluated 6 months post-second dose (D201), 100% of vaccinated individuals retained binding antibodies, and ∼95% retained neutralizing antibodies; interferon gamma (IFN-γ) and interleukin 4 (IL-4) responses directed against the ancestral S protein were also still detectable in ∼94% and ∼92% of vaccinees respectively. Variant-specific, cross-reactive neutralizing antibody (NAb) levels were assessed at D42 and D201 using both live wild-type and pseudovirion assays (Alpha, Beta, Gamma) or the wild-type assay alone (Delta, Omicron). In the wild-type assay, broad cross-reactivity was detected against all variants at D42 (100% Alpha and Delta, 94% Beta and Gamma, 74% Omicron). At D201, cross-reactive antibodies were detectable in almost all participants against Alpha, Gamma and Delta variants (94%) and the Beta variant (83%) and in a smaller proportion against Omicron (44%). Results were similar in the pseudovirion assay (D42, 100% cross-reactivity to Alpha and Gamma variants, 95% to Beta variant, D201, 94% for Alpha, Beta and Gamma variants). These data suggest that two doses of 3.75 µg CoVLP+AS03 elicit a durable and cross-reactive response that persists for at least 6 months post-vaccination.
Genetic variants associated with cross-disorder and disorder-specific risk for psychiatric disorders are enriched at epigenetically active sites in peripheral lymphoid cells
Authors: Lynall Mary-Ellen , Soskic Blagoje , Hayhurst James , Schwartzentruber Jeremy , Levey Daniel F. , Pathak Gita A. , Polimanti Renato , Gelernter Joel , Stein Murray B. , Trynka Gosia , Clatworthy Menna R. , Bullmore Ed
Published: August 2021

Multiple psychiatric disorders have been associated with abnormalities in both the innate and adaptive immune systems. The role of these abnormalities in pathogenesis, and whether they are driven by psychiatric risk variants, remains unclear. We tested for enrichment of GWAS variants associated with multiple psychiatric disorders (cross-disorder or trans-diagnostic risk), or 5 specific disorders (cis-diagnostic risk), in regulatory elements in immune cells. We used three independent epigenetic datasets representing multiple organ systems and immune cell subsets. Trans-diagnostic and cis-diagnostic risk variants (for schizophrenia and depression) were enriched at epigenetically active sites in brain tissues and in lymphoid cells (T, B and NK cells), especially stimulated CD4+ T cells. There was no evidence for enrichment of either trans-risk or cis-risk variants for schizophrenia or depression in myeloid cells. This suggests a model where stimuli (e.g. infection) activate T cells to unmask the effects of psychiatric risk variants, contributing to the pathogenesis of mental health disorders.
Defective X-gating caused byde novogain-of-function mutations inKCNK3underlies a developmental disorder with sleep apnea
Authors: Sörmann Janina , Schewe Marcus , Proks Peter , Jouen-Tachoire Thibault , Rao Shanlin , Riel Elena B. , Agre Katherine E. , Begtrup Amber , Dean John , Descartes Maria , Fischer Jan , Gardham Alice , Lahner Carrie , Mark Paul R. , Muppidi Srikanth , Pichurin Pavel N. , Porrmann Joseph , Schallner Jens , Smith Kirstin , Straub Volker , Vasudevan Pradeep , Willaert Rebecca , Carpenter Elisabeth P. , Rödström Karin E.J. , Hahn Michael G. , Müller Thomas , Baukrowitz Thomas , Hurles Matthew E. , Wright Caroline F. , Tucker Stephen J.
Published: August 2021

Sleep apnea is a common disorder that represents a global public health burden.KCNK3encodes TASK-1, a K+channel implicated in the control of breathing, but its link with sleep apnea remains poorly understood. Here we describe a novel developmental disorder with sleep apnea caused by rarede novogain-of-function mutations inKCNK3. The mutations cluster around the ‘X-gate’, a gating motif which controls channel opening, and produce overactive channels that no longer respond to inhibition by G-protein coupled receptor pathways, but which can be inhibited by several clinically relevant drugs. These findings demonstrate a clear role for TASK-1 in sleep apnea and identify possible therapeutic strategies.
Safety and Immunogenicity of CpG 1018 and Aluminium Hydroxide-Adjuvanted SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901: A Large-Scale Double-Blind, Randomised, Placebo-Controlled Phase 2 Trial
Authors: Szu-Min Hsieh , Liu Ming-Che , Chen Yen-Hsu , Lee Wen-Sen , Hwang Shinn-Jang , Cheng Shu-Hsing , Ko Wen-Chien , Hwang Kao-Pin , Wang Ning-Chi , Lee Yu-Lin , Lin Yi-Ling , Shih Shin-Ru , Huang Chung-Guei , Liao Chun-Che , Liang Jian-Jong , Chang Chih-Shin , Chen Charles , Lien Chia En , Tai I-Chen , Lin Tzou-Yien
Published: August 2021

Background

We have assessed the safety and immunogenicity of the COVID-19 vaccine MVC-COV1901, a recombinant protein vaccine containing prefusion-stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide.

Methods

This is a phase 2, prospective, randomised, double-blind, placebo-controlled, and multi-centre study to evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 vaccine candidate MVC-COV1901. The study comprised 3,844 participants of ≥ 20 years who were generally healthy or with stable pre-existing medical conditions. The study participants were randomly assigned in a 6:1 ratio to receive either MVC-COV1901 containing 15 μg of S-2P protein or placebo containing saline. Participants received two doses of MVC-COV1901 or placebo, administered 28 days apart via intramuscular injection. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from Day 1 (the day of first vaccination) to Day 57 (28 days after the second dose). Immunogenicity of MVC-COV1901 was assessed through geometric mean titres (GMT) and seroconversion rates (SCR) of neutralising antibody and antigen-specific immunoglobulin. This clinical trial is registered at ClinicalTrials.gov: NCT04695652.

Findings

From the start of this phase 2 trial to the time of interim analysis, no vaccine-related Serious Adverse Events (SAEs) were recorded. The most common solicited adverse events across all study participants were pain at the injection site (64%), and malaise/fatigue (35%). Fever was rarely reported (<1%). For all participants in the MVC-COV1901 group, at 28 days after the second dose against wild type SARS-CoV-2 virus, the GMT was 662·3 (408 IU/mL), the GMT ratio was 163·2, and the seroconversion rate was 99·8%.

Interpretation

MVC-COV1901 shows good safety profiles and promising immunogenicity responses. The current data supports MVC-COV1901 to enter phase 3 efficacy trials and could enable regulatory considerations for Emergency Use Authorisation (EUA).

Funding

Medigen Vaccine Biologics Corporation and Taiwan Centres for Disease Control.
Analysis of Whole Genome Sequencing in a Cohort of Individuals with PHACE Syndrome Suggests Dysregulation of RAS/PI3K Signaling
Authors: Partan Elizabeth S. , Blei Francine , Chamlin Sarah L. , Davies Olivia M. T. , Drolet Beth A. , Frieden Ilona J. , Karakikes Ioannis , Lin Chien-Wei , Mancini Anthony J. , Metry Denise , Oro Anthony , Stefanko Nicole S. , Sundaram Laksshman , Tutaj Monika , Urban Alexander E. , Wang Kevin C. , Zhu Xiaowei , Sobreira Nara , Siegel Dawn H.
Published: August 2021

The acronym PHACE stands for the co-occurrence of posterior brain fossa malformations, hemangiomas, arterial anomalies, cardiac defects, and eye abnormalities. The majority of patients have a segmental hemangioma and at least one developmental structural anomaly. The etiology and pathogenesis are unknown. Here we discuss the candidate causative genes identified in a de novo analysis of whole genome sequencing of germline samples from 98 unrelated trios in which the probands had PHACE, all sequenced as part of the Gabriella Miller Kids First Pediatric Research Program. A g:Profiler pathway analysis of the genes with rare, de novo variants suggested dysregulation of the RAS/MAPK and PI3K/AKT pathways that regulate cell growth, migration, and angiogenesis. These findings, along with the developmental anomalies and the vascular birthmark, support including PHACE within the RASopathy family of syndromes.
Occupational risk of SARS-CoV-2 infection and reinfection during the second pandemic surge: a cohort study
Authors: Leidi Antonio , Berner Amandine , Dumont Roxane , Dubos Richard , Koegler Flora , Piumatti Giovanni , Vuilleumier Nicolas , Kaiser Laurent , Balavoine Jean-François , Trono Didier , Pittet Didier , Chappuis François , Kherad Omar , Courvoisier Delphine , Azman Andrew S , Zaballa María-Eugenia , Guessous Idris , Stringhini Silvia ,   SEROCoV-WORK+ study group
Published: August 2021

Objectives

This cohort study including essential workers, assessed the□risk and incidence of SARS-CoV-2□infection during the second surge of COVID-19 according to baseline serostatus and occupational sector.

Methods

Essential workers were selected from a seroprevalence survey cohort in Geneva, Switzerland and were linked to a state centralized registry compiling SARS-CoV-2 infections. Primary outcome was the number of virologically-confirmed infections from serological assessment (between May and September 2020) to January 25, 2021, according to baseline antibody status and stratified by three pre-defined occupational groups (occupations requiring sustained physical proximity, involving brief regular contact or others). Secondary outcomes included the incidence of infection.

Results

10457 essential workers were included (occupations requiring sustained physical proximity accounted for 3057 individuals, those involving regular brief contact, 3645, and 3755 workers were classified under “Other essential occupations”). After a follow-up period of over 27 weeks, 5 (0.6%) seropositive and 830 (8.5%) seronegative individuals had a positive SARS-CoV-2 test, with an incidence rate of 0.2 (95% CI 0.1 to 0.6) and 3.2 (95% CI 2.9 to 3.4) cases per person-week, respectively. Incidences were similar across occupational groups. Seropositive essential workers had a 93% reduction in the hazard (HR of 0.07, 95% CI 0.03 to 0.17) of having a positive test during follow-up with no significant between-occupational group difference.

Conclusions

A ten-fold reduction in the hazard of being virologically tested positive was observed among anti-SARS-CoV-2 seropositive essential workers regardless of their sector of occupation, confirming the seroprotective effect of a previous SARS-CoV2 exposure at least six months after infection.

Key messages

What is already known about this subject?

Risk of SARS-CoV-2 reinfection is low in the general population and among healthcare workers.

What are the new findings?

A ten-fold reduction of risk of being virologically tested positive reinfection is observed among anti-SARS-CoV-2 seropositive essential workers of different activity sectors, regardless of their occupation-related risk of exposure.

How might this impact on policy or clinical practice in the foreseeable future?

Vaccination could be delayed in individuals with previous history of SARS-CoV-2 infection with serologic confirmation, regardless of their occupational exposure. These observations need to be confirmed for new SARS-CoV-2 variants.
Awake Prone Position in Hypoxemic Patients with Coronavirus Disease 19 (COVI-PRONE): A Study protocol and Statistical Analysis Plan for Randomized Clinical Trial
Authors: Duhailib Zainab Al , Arabi Yaseen M , Culgin Sarah , Weatherald Jason , Parhar Ken Kuljit S. , Nelson Kate , Tamim Hani , Alhazzani Waleed ,   the COVI-PRONE Trial investigators
Published: August 2021

Background

Coronavirus disease 2019 (COVID-19), may progress to respiratory failure requiring invasive mechanical ventilation. Due to ventilator shortage and healthcare systems strain, affordable interventions such as awake prone positioning has been used to improve oxygenation, however, the effect of this intervention on patient-important outcomes is uncertain. The COVI-PRONE trial aims to determine if awake prone positioning in hypoxemic COVID-19 patients reduces the need for invasive mechanical ventilation.

Study design

A pragmatic, multicenter, international, parallel-group, and stratified randomized controlled trial, aiming to enrol 400 hospitalized adults with COVID-19.

Participants

The target population is hospitalized adults with confirmed or suspected COVID-19, hypoxemia that requires ≥40% oxygen or ≥ 5 L/min by nasal cannula, and abnormal chest x-ray. We will exclude patients with any of the following: immediate need for intubation; altered mental status; contraindication to prone positioning; hemodynamic instability; body mass index > 40 kg/m2; third trimester pregnancy; do not intubate status; previous enrolment or intubation within the same hospital admission; and prone positioning for more than one day prior to randomization.

Study intervention and control

Following informed a priori or deferred consent, eligible patients will be centrally randomized to either the intervention arm (prone positioning) or standard of care (no prone positioning). Patients randomized to the prone position will be required to either self-prone or assist-prone for a total of eight to ten hours per day until they meet pre-specified stopping criteria.

Study outcomes

The primary outcome is invasive mechanical ventilation at 30-days of randomization. Other outcomes include mortality at 60 days, invasive and non-invasive mechanical ventilation free days at 30 days, hospital length of stay at 60 days, days alive and outside of the hospital at 60 days, complications of proning, and serious adverse events.