bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Preoperative Epidural Steroid Injections Increase the Risk of Infection After Lumbar Spine Surgery?
Authors: Kreitz Tyler M. , Mangan John , Schroeder Gregory D. , Kepler Christopher K. , Kurd Mark F. , Radcliff Kris E. , Woods Barrett I. , Rihn Jeffery A. , Anderson D. Greg , Vaccaro Alexander R. , Hilibrand Alan S.
Published: October 2020

Study Design.

Retrospective study.

Objective.

To elucidate an association between preoperative lumbar epidural corticosteroid injections (ESI) and infection after lumbar spine surgery.

Summary of Background Data.

ESI may provide diagnostic and therapeutic benefit; however, concern exists regarding whether preoperative ESI may increase risk of postoperative infection.

Methods.

Patients who underwent lumbar decompression alone or fusion procedures for radiculopathy or stenosis between 2000 and 2017 with 90 days follow-up were identified by ICD/CPT codes. Each cohort was categorized as no preoperative ESI, less than 30 days, 30 to 90 days, and greater than 90 days before surgery. The primary outcome measure was postoperative infection requiring reoperation within 90 days of index procedure. Demographic information including age, sex, body mass index (BMI), Charlson Comorbidity Index (CCI) was determined. Comparison and regression analysis was performed to determine an association between preoperative ESI exposure, demographics/comorbidities, and postoperative infection.

Results.

A total of 15,011 patients were included, 5108 underwent fusion and 9903 decompression only. The infection rate was 1.95% and 0.98%, among fusion and decompression patients, respectively. There was no association between infection and preoperative ESI exposure at any time point (1.0%, P = 0.853), ESI within 30 days (1.37%, P = 0.367), ESI within 30 to 90 days (0.63%, P = 0.257), or ESI > 90 days (1.3%, P = 0.277) before decompression surgery. There was increased risk of infection in those patients undergoing preoperative ESI before fusion compared to those without (2.68% vs. 1.69%, P = 0.025). There was also increased risk of infection with an ESI within 30 days of surgery (5.74%, P = 0.005) and when given > 90 days (2.9%, P = 0.022) before surgery. Regression analysis of all patients demonstrated that fusion (P < 0.001), BMI (P < 0.001), and CCI (P = 0.019) were independent predictors of postoperative infection, while age, sex, and preoperative ESI exposure were not.

Conclusion.

An increased risk of infection was found in patients with preoperative ESI undergoing fusion procedures, but no increased risk with decompression only. Fusion, BMI, and CCI were predictors of postoperative infection.

Level of Evidence: 3
Irreversible epidermal growth factor receptor inhibitor Z25h exhibits pronounced inhibition on non-small cell lung adenocarcinoma cell line Hcc827
Authors: Wang Jin , Tan Shuai , Yan Ping-ping , Xiao Xue , Zhang Hao , Zhang San-qi , Li Wei , Cao Yong-xiao , Wang Hong-ying
Published: October 2020

The epidermal growth factor receptor (EGFR) signaling is frequently activated in lung cancer. In our previous study, a new class of compounds containing pyrido[3,4-d]pyrimidine scaffold with an acrylamide moiety was designed as irreversible EGFR-tyrosine kinase inhibitors to overcome acquired EGFR-T790M resistance. In this study, we selected the most promising compound Z25h to further investigate its effects and the underlying mechanism against non-small cell lung adenocarcinoma cells in vitro. Four different non-small cell lung adenocarcinoma cell lines were selected to test the antiviability profile of Z25h, and Hcc827 was the most sensitive to the drug treatment. Z25h caused cell cycle arrest at G0-G1 phase, and triggered strong early apoptosis in Hcc827 cells at 0.1 μM and late apoptosis in A549, H1975 and H1299 cells at 10 μM by 48 h treatment. Z25h inhibited the activation of EGFR and its downstream PI3K/AKT/mTOR pathway in the four tested cell lines, leading to the inhibition of cellular biosynthetic and metabolic processes and the promotion of apoptotic process. However, the effect of Z25h on mitogen-activated protein kinase pathway varies from cell lines. In addition, Z25h sensitized H1975 cells to X-ray radiation, and it also enhanced the radiation effect on A549 cells, while no obvious effect of Z25h was observed on the cell viability inhibition of H1299 cells induced by radiation. Hereby, Z25h might be considered as a potential therapeutic drug candidate for non-small cell lung adenocarcinoma treatment.
Rapid Switch From Subcutaneous to Intravenous Treprostinil in Precapillary Pulmonary Hypertension by Pump Implantation
Authors: Steringer-Mascherbauer Regina , Maria Lummerstorfer , Reinhold Függer , Elisabeth Sigmund , Charlotte Huber , Dagmar Engleder , Uwe Fröschl , Josef Aichinger
Published: October 2020

Limited data are available on the transition from subcutaneous to intravenous prostacyclin in precapillary pulmonary hypertension. We performed a retrospective analysis of all patients who were switched from subcutaneous to intravenous treprostinil with an implantable infusion pump. We included 85 consecutive, clinically stable patients (mean age 66 years and range 16–85), who had been treated with subcutaneous treprostinil for mean 9 months (range 1–78) before pump implantation. An interdisciplinary expert panel defined standards for this procedure before the first implantation. As the first patient experienced a significant hypotensive episode indicating treprostinil overdose postoperatively, the time span to stop subcutaneous treprostinil was reduced to 60 minutes for all following patients. No events associated with the switch from subcutaneous to intravenous treprostinil were observed during postoperative hospital stay in 84 (98.8%) patients. Taking into account a likely depot effect of subcutaneous treprostinil patients can safely be switched to the intravenous route by the implantation of an infusion pump.
Detection of Protein Aggregation and Proteotoxicity Induced by Angiotensin II in Vascular Smooth Muscle Cells
Authors: Cicalese Stephanie , Okuno Keisuke , Eguchi Satoru
Published: October 2020

Disruption of protein quality control occurs with aging and cardiovascular pathologies including arterial stiffness and hypertension. Angiotensin II (Ang II) is believed to induce endoplasmic reticulum stress in vascular smooth muscle cells (VSMCs), thus contributing to vascular remodeling and dysfunction. However, whether Ang II increases formation of protein aggregates and mediates proteotoxicity in VSMCs remain obscure. Accordingly, this study aimed to establish a quantitative method of protein aggregate detection induced by Ang II and to investigate their potential involvement in inflammatory and senescence responses. Proteostat staining showed increased aggregate numbers per cell on Ang II exposure. Immunoblot analysis further showed an increase in preamyloid oligomer presence in a detergent insoluble protein fraction purified from VSMCs stimulated with Ang II. Moreover, these responses were attenuated by treatment with chemical chaperone, 4-phenylbutyrate. 4-phenylbutyrate further blocked Ang II-induced senescence associated β-galactosidase activity and THP-1 monocyte adhesion in VSMCs. These data suggest that Ang II induces proteotoxicity in VSMCs which likely contributes to aging and inflammation in the vasculature.
Sixty-seven Hours After Cesarean Successfully Redo Prosthetic Mitral Valve Leaflet Replacement at 29th Gestational Week: A Case Report and Literature Review
Authors: Wang Yu-Guang , Xie Bao-Dong , Sun Jing-Xia
Published: October 2020

On April 3, 2020, a 37-year-old woman successfully completed heart valve replacement after cesarean section 67 hours in the First Affiliated Hospital of Harbin Medical University.The woman underwent the mechanical mitral valve replacement in the same hospital 10 years ago. She used low molecular weight heparin instead of warfarin, when she realized her pregnancy. On March 25, 2020 (28+5 weeks of gestation), due to New York Heart Association class IV, severe pneumonia, type I respiratory failure, the patient was admitted to the hospital for treatment. Three days later, she discharged herself from hospital by refusing the cesarean section. The next day she was re-admitted to the ward because of the worsen symptoms and oliguria. Cesarean section was performed 50 hours after admission. The neonate was 1 400 g; Apgar score was 5 in 1 minute, 8 in 5 minutes, transferred to neonatal intensive care unit. Because of the unrecovered heart function, she was confirmed stuck mechanical prosthetic mitral valves. On April 3, 2020, through multi-disciplinary cooperation, the patient was safe without any life-threatening emergency. Eleven days after the replacement, the patient was discharged smoothly, so was the neonate 33 days after delivery.
Primary Melanoma of the Lacrimal Sac Treated With Pembrolizumab
Authors: Salloum George , Dryden Stephen , Meador Andrew G. , Kurochkin Philip D. , Chamberlain Benjamin K. , Fasig John H. , Waynick Christopher A. , Wesley Ralph E. , Everman Kelly R.
Published: October 2020

Primary melanoma of the lacrimal sac is a rare entity, with high mortality and a propensity for recurrence. This report details a patient with widely metastatic melanoma discovered after biopsy of abnormal lacrimal sac tissue during routine dacryocystorhinostomy. The patient subsequently underwent local excision and treatment with pembrolizumab. At the time of this writing, it has been 24 months since the original diagnosis with resolution of his lacrimal and orbital lesions and improvement in all metastatic lesions. This case highlights the growing use of cancer genomics and immunotherapeutic agents in orbital aspects of oncology and reinforces the role of a multidisciplinary approach in the treatment of such diseases.
Effect of anti-inflammatory regimen on early postoperative inflammation after cataract surgery
Authors: Erichsen Jesper H. , Forman Julie L. , Holm Lars M. , Kessel Line
Published: October 2020

Purpose:

To investigate whether a combination of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids were superior in controlling early postoperative inflammation after cataract surgery compared with topical NSAIDs alone and with dropless surgery where a sub-Tenon depot of steroid was placed during surgery.

Setting:

Department of Ophthalmology, Rigshospitalet-Glostrup, Denmark.

Design:

Prospective randomized controlled trial with masked statistical analyses.

Methods:

Patients undergoing phacoemulsification for age-related cataract were randomized to 1 of 5 regimens: ketorolac and prednisolone eyedrops combined (Pred+NSAID-Pre [control group] and Pred+NSAID-Post group) vs ketorolac monotherapy (NSAID-Pre and NSAID-Post groups) vs sub-Tenon depot of dexamethasone (dropless group). Drops were used until 3 weeks postoperatively, starting 3 days preoperatively in the Pre groups and on the day of surgery in the Post groups. Aqueous flare was measured at baseline and 3 days postoperatively.

Results:

Four hundred fifty-six participants, with a mean age of 72.1 (SD 7.0) years and 283 (62%) women, were included. Flare increased significantly more in the dropless group compared with the control group (Pred+NSAID-Pre), but none of the other groups differed significantly from the control group. Intraocular pressure decreased in all groups but significantly less in groups receiving prednisolone eyedrops (Pred+NSAID-Pre and Pred+NSAID-Post groups) compared with NSAID monotherapy and dropless groups. No differences in postoperative visual acuity were found compared with the control group.

Conclusions:

No differences were found between groups randomized to NSAID monotherapy or combination of NSAID and steroid in controlling early inflammation after cataract surgery, but sub-Tenon depot of dexamethasone was less efficient. Initiating prophylactic eyedrops prior to surgery did not influence early postoperative anterior chamber inflammation.
Changing practice patterns in European cataract surgery as reflected in the European Registry of Quality Outcomes for Cataract and Refractive Surgery 2008 to 2017
Authors: Lundström Mats , Dickman Mor , Henry Ype , Manning Sonia , Rosen Paul , Tassignon Marie-José , Young David , Behndig Anders , Stenevi Ulf
Published: October 2020

Purpose:

To study practice patterns in European cataract surgery over a 10-year period.

Setting:

European clinics affiliated to the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO).

Design:

Registry cohort study.

Methods:

The EUREQUO contains preoperative, intraoperative, and postoperative parameters reported by surgeons in many European clinics. All data reported to the registry are anonymized. Preoperative parameters included age, sex, visual acuity, target refraction, ocular comorbidity, and surgical difficulties. Surgical data included anesthesia, surgical technique, intraocular lens optic biomaterial, and complications. Postoperative parameters included visual acuity, refraction, and short-term complications.

Results:

During the study period (January 1, 2008, to December 31, 2017), a total of 2 714 108 cataract extractions were reported to the EUREQUO. Preoperative data changed over time, with decreases in mean age (74.5–73.0 years), proportion of women from 60.6% (100 373/165 628) to 57.2% (174 908/305 845), and proportion of coexisting eye diseases from 30.0% (49 638/165 650) to 27.0% (82 704/305 846) and with improvements in preoperative visual acuity (mean logarithm of minimum angle of resolution [logMAR] 0.46 to 0.37). The use of topical anesthesia increased over time from 28.1% (26 238/93 320) to 71.7% (130 525/182 083). Surgical complications showed a significant decrease from 2.5% (4107/165 650) to 1.2% (3573/305 846). The visual outcome improved over time (mean logMAR 0.08 to 0.05), as did the absolute median prediction error (0.38 diopter [D] to 0.28 D).

Conclusions:

Trends in European cataract surgery practice patterns from 2008 to 2017 have moved toward younger patients with better preoperative visual acuity, fewer surgical complications, and better predicted refractions and visual outcomes.
Handover From the Emergency Department to Inpatient Units
Authors: Tobiano Georgia , Ryan Christine , Jenkinson Kim , Scott Lucie , Marshall Andrea P.
Published: October 2020

Background:

Intrahospital handovers are high risk. Standardization of content and process is recommended.

Local Problem:

Emergency department to inpatient unit handovers were inefficient.

Interventions:

The intervention was a standardized operating protocol, including checklist and procedures.

Methods:

The intervention was coproduced and prototyped. Handovers were observed for intervention adherence, and the Handover Evaluation Scale was used to measure nurses' perceived quality of handover.

Results:

The handover had 3 steps. Step 1 had more content, prompting by the receiver, and family participation postintervention. Step 3 was shorter in duration, had less content, and occurred at the bedside more postintervention. Receiving nurses were able to ask questions and found that information provided was timely, current, and easy to follow. Sending nurses perceived that handover was less succinct postimplementation, despite decreases in handover duration and repetition of information.

Conclusions:

This project has triggered ongoing improvement initiatives, necessary to keep accommodating the needs of nurses that work across boundaries.
Do Falls and Other Safety Issues Occur More Often During Handovers When Nurses Are Away From Patients? Findings From a Retrospective Study Design
Authors: Demaria Jessica , Valent Francesca , Danielis Matteo , Bellomo Fabrizio , Farneti Federico , Bressan Valentina , Palese Alvisa
Published: October 2020

Background:

No studies have assessed the differences in the incidences of falls and other patient safety events (PSEs) during handovers performed away from patients compared with when nurses are on the unit.

Purpose:

The primary aim was to explore the incidence of falls and their severity during handovers compared with during nonhandover times; the secondary aim was to explore the occurrence of other PSEs during handover versus nonhandover times.

Methods:

This was a retrospective study of all PSEs that occurred from 2013 to 2017 in a large Italian academic trust.

Results:

There were 1966 falls and 1523 other PSEs. The incidence of falls per 100 hours was 4.9 during handovers and 4.4 during nonhandover times. The incidences of other PSEs were 2.9 and 3.5, respectively. No significant differences in fall outcome severity emerged.

Conclusions:

No differences emerged in the occurrence of falls during handovers performed away from patients and when nurses were on the unit. Other PSEs decreased in occurrence during handovers as compared with other times during the shifts.
Motor Evoked Potentials Double Train Stimulation: Optimal Number of Pulses per Train
Authors: Kale Emily B. , Lutz Michael W. , Husain Aatif M.
Published: October 2020

Purpose:

In neurophysiologic intraoperative monitoring, double train transcranial electrical stimulation (dt-TES) for motor evoked potentials (MEP) consists of an initial, facilitating train of stimuli followed by a second, testing, train. The optimal number of pulses per train has not been determined. The authors wanted to determine the optimal combination of pulses per train that produced the highest MEP amplitude.

Methods:

Dt-TES of 4 + 4, 2 + 7, and 7 + 2 pulses were attempted in 20 patients and compared with single train TES of nine pulses. Latencies of the MEP responses were also compared. Additionally, statistical comparisons were made of the differences between the amplitude and latency measurements within the patients.

Results:

The mean age of the patients was 44.3 years (range, 9–84 years). Dt-TES of 2 + 7 pulses resulted in significantly higher mean amplitudes than dt-TES of 4 + 4 and 7 + 2 pulses and single train TES of nine pulses (p < 0.001). The MEP latency with dt-TES of 2 + 7 pulses was longer than the latencies of single train TES of nine pulses and dt-TES of 4 + 4 and 7 + 2 pulses.

Conclusions:

Asymmetric dt-TES with 2 + 7 pulses improved MEP amplitudes. This type of stimulation may be preferable to single train TES and dt-TES with symmetric pulse trains.
Is sleep apnea-hypopnea index relevant for impaired brain perfusion and desaturation in patients with severe obstructive sleep apnea syndromes?
Authors: Zhang Zhongxing , Qi Ming , Hügli Gordana , Khatami Ramin
Published: October 2020

Background

Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder with the prevalence of 9-38% in the general population. Severe OSAS defined as apnea-hypopnea index (AHI) ≥ 30/h is a major risk factor for developing cerebro-cardiovascular diseases like stroke. Treatments such as continuous positive airway pressure (CPAP) therapy are recommended for those patients because untreated OSA can cause tremendous medical expenses and economic burden. Understanding the mechanisms of how repetitive sleep apneas/hypopneas induce changes in cerebral hemodynamics in severe OSAS is crucial for the understanding of disease severity, disease progression in brain damage and the treatment efficacy. However, these mechanisms and the association between AHI and the induced changes in cerebral hemodynamics in severe OSAS are essentially unknown. Using a stepwise incremental CPAP titration protocol we aim to identify the most relevant physiological factors including AHI and their quantitative contributions to cerebral hemodynamic changes before and during CPAP treatment in severe OSAS patients.

Methods and findings

29 newly diagnosed severe OSAS patients underwent incremental CPAP titration during polysomnography recordings: 1-h sleep without CPAP served as self-controlled baseline followed by stepwise increments of 1-cmH2O pressure per-hour starting from 5-8 cmH2O individually. Frequency-domain near-infrared spectroscopy measured the changes in blood volume (BV) and oxygen saturation (StO2) in the left forehead. The coefficients of variation of BV (CV-BV) and the decreases of StO2 (de-StO2) during more than 2000 respiratory events were predicted by various predictors including AHI using linear mixed-effect models, respectively. The best predictors were automatically selected by stepwise regression. Surprisingly, AHI was excluded from the final selected models. Longer events and apneas rather than hypopneas induce larger changes in CV-BV and stronger cerebral desaturation. Respiratory events occurring during higher baseline StO2 before their onsets, during rapid-eye-movement sleep and those associated with higher heart rate (HR) during the events trigger smaller changes in CV-BV and de-StO2. CPAP pressures attenuate the changes in CV-BV and de-StO2.

Conclusions

In severe OSAS the length and the type of respiratory event rather than widely used AHI may be better parameters to indicate the severity of cerebral vascular damage. Thus both, length and type of respiratory events should be considered as predictors of cerebro-cardiovascular events in future epidemiological studies and in clinical practice. OSAS patients with profound long apnea events need to pay special attention and quickly treated with CPAP therapy as it can restore the induced cerebral hemodynamic changes.
Intrinsic Signal Amplification by Type-III CRISPR-Cas Systems Provides a Sequence-Specific Viral Diagnostic
Authors: Santiago-Frangos Andrew , Hall Laina N. , Nemudraia Anna , Nemudryi Artem , Krishna Pushya , Wiegand Tanner , Wilkinson Royce A. , Snyder Deann T. , Hedges Jodi F. , Jutila Mark A. , Taylor Matthew P. , Wiedenheft Blake
Published: October 2020

To combat viral pandemics, there is an urgent need for inexpensive new technologies that enable fast, reliable, and scalable detection of viruses. Here we repurposed the type III CRISPR-Cas system for sensitive and sequence specific detection of SARS-CoV-2 in an assay that can be performed in one hour or less. RNA recognition by type III systems triggers Cas10-mediated polymerase activity, which simultaneously generates pyrophosphates, protons and cyclic oligonucleotides. We show that amplified products of the Cas10-polymerase are detectable using colorimetric or fluorometric readouts.
Characteristics of COVID-19 Clinical Trials in India Based on the Registration Data on CTRI (Clinical Trials Registry- India): a cross-sectional analysis
Authors: Sathiyarajeswaran P , Shree Devi MS , Kanakavalli K , Vinod NP
Published: October 2020

Objectives

The 2019 pandemic of coronavirus disease (COVID-19) has prompted several efforts to find safe and effective drugs, but little is understood as to where early efforts were centered. Several clinical trials, both Allopathy and AYUSH medicines have been registered in the Clinical Trial Registry of India (CTRI). We aimed to characterize and extract relevant data registered under CTRI for COVID-19.

Materials and Methods

A cross-sectional analysis was performed of clinical trials for the treatment of COVID-19 that were registered in the Clinical Trial Registry of India (CTRI) from 1st March 2020 to 22nd June 2020. Relevant trial records were downloaded, deduplicated, and independently analyzed by three reviewers.

Main outcomes

Trial intervention, design, sponsorship, phase of the trial, and indicated outcomes.

Results

233 COVID-19 clinical trials, was registered from India in CTRI. Out of these, 146 were Interventional trials, 84 Observational trials, and three Post-marketing surveillance. Questionnaire and survey-based intervention occupy a significant portion. Randomized control trials are large in number 37.8% than non-randomized. 20% of the trials were recruiting patients, and the Research institution (34%) sponsored more than half of the trials. Global trials are minimal, occupying 3% of total trials and Indian trials were 97%. In most of the trials, the interventional agent is either multiple drug combinations or compound drug formulations compared to single drug administration. Among the trials, 46 Allopathic interventions, 41 Ayurveda interventions, 14 Homeopathy interventions, one in Unani, and 2 in yoga and Naturopathy.

Conclusion

This study will provide a background of COVID-19 clinical trials registered in CTRI and provide specific issues observed related to clinical trial designs, which offer information to perform clinical trials on COVID-19
Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) is an effective alternative for SARS-CoV-2 molecular detection in middle-income countries
Authors: Escalante-Maldonado Oscar , Vidal-Anzardo Margot , Donaires Fernando , Solis-Sanchez Gilmer , Gallesi Italo , Pampa-Espinoza Luis , Huaringa Maribel , Serrano Nancy Rojas , García Coralith , Angles-Yanqui Eddie , Gavilán Ronnie Gustavo , Durães-Carvalho Ricardo , Cabezas Cesar , Simas Paulo Vitor Marques
Published: October 2020

Molecular diagnosis of SARS-CoV-2 in developing countries is still a big challenge. The reference standard, RT-qPCR, recommended by WHO, is not widely available, difficulting early identification of cases. Furthermore, the transport logistic between the sample collection point and the laboratory facilities can alter the samples, producing false negative results. RT-LAMP is a cheaper, simpler molecular technique that can be an interesting alternative to be offered in hospital laboratories. We present the evaluation of a RT-LAMP for diagnosis of SARS-CoV-2 in two steps: the laboratory standardization and the clinical validation, comparing it with the standard RT-qPCR. In the standardization phase, limit of detection and robustness values were obtained using RNA from a Peruvian SARS-CoV-2 strain. It presented 100% agreement between triplicates (RT-LAMP agreement with all RT-qPCR reactions that presented Ct ≤ 30) and robustness (RT-LAMP successful reactions with 80% reaction volume and 50% primer concentration). 384 nasal and pharyngeal swabs collected from symptomatic patients and stored in the INS biobank were tested and we obtained 98.75%, 87.41%, 97.65% and 92.96% for specificity, sensitivity, positive predictive value and negative predictive values respectively. Then, 383 samples from symptomatic patients with less than 15 days of disease, were tested both with the RT-LAMP and with the RT-qPCR, obtaining e 98.8%, 88.1%, 97.7% y 93.3% of specificity, sensitivity, positive predictive value and negative predictive values respectively. The laboratory standardization and the clinical validation presented the same value by Kappa-Cohen index (0.88) indicating an almost perfect agreement between RT-LAMP and RT-qPCR for molecular detection of SARS-CoV-2. We conclude that this RT-LAMP protocol presented high diagnostic performance values and can be an effective alternative for COVID-19 molecular diagnosis in hospitals, contributing to early diagnosis and reducing the spread of virus transmission in the Peruvian population.
Long term impact of coal mine fire smoke on lung mechanics in exposed adults
Authors: Holt Nicolette R , Gao Caroline X. , Borg Brigitte M , Brown David , Broder Jonathan C , Ikin Jillian , Makar Annie , McCrabb Thomas , Nilsen Kris , Thompson Bruce R , Abramson Michael J.
Published: October 2020

In 2014, a six-week long fire at the Hazelwood open cut coal mine exposed residents in the adjacent town of Morwell to high concentrations of fine particulate matter with an aerodynamic diameter <2.5μm (PM2.5). The long-term health consequences are being evaluated as part of the Hazelwood Health Study (HHS).

Approximately 3.5 to 4 years after the mine fire, adults from Morwell (n=346) and the comparison town Sale (n=173) participated in the longitudinal Respiratory Stream of the HHS. Individual fire-related PM2.5exposure was retrospectively modelled. Lung mechanics were assessed using the forced oscillation technique (FOT), which utilises pressure waves to measure respiratory system resistance (Rrs) and reactance (Xrs). Multivariate linear regression was used to evaluate associations between PM2.5and transformed Rrs5, area under the reactance curve (AX5) and Xrs5 controlling for key confounding factors.

There were clear dose-response relationships between increasing mine fire PM2.5and worsening lung mechanics, including a reduction in post-bronchodilator Xrs5 and an increase in AX5. A 10 μg/m3increase in mine fire related PM2.5was associated with a 0.015 (95%CI: 0.004, 0.027) reduction in exponential(Xrs5) post bronchodilator, which was comparable to 4.7 years of aging. Similarly, the effect of exposure was associated with a 0.072 (0.005, 0.138) increase in natural log(AX5) post-bronchodilator, equivalent to 3.9 years of aging.

This is the first study using FOT in adults evaluating long term respiratory outcomes after a medium-term ambient PM2.5exposure to coal mine fire smoke. These results should inform public health policies and planning for future events.
Chronic Obstructive Pulmonary Disease in adults exposed to fine particles from a coal mine fire
Authors: Prasad Shivonne , Gao Caroline , Borg Brigitte , Broder Jonathan , Brown David , Ikin Jillian , Makar Annie , McCrabb Tom , Hoy Ryan , Thompson Bruce , Abramson Michael J.
Published: October 2020

Introduction

In 2014 the Hazelwood open cut coal mine burned for six weeks, exposing nearby residents to fine particulate matter (PM2.5). The long-term health consequences are being evaluated as part of the Hazelwood Health Study (HHS). These analyses explore the association between PM2.5 and chronic obstructive pulmonary disease (COPD).

Methods

A sample of 346 exposed, and 173 unexposed, adults participated in the longitudinal Respiratory Stream of the HHS. Participants underwent spirometry and gas transfer measurements and answered validated respiratory questionnaires 3.5-4 years after the fire. Individual level mine fire-related PM2.5 exposure was modelled. Multivariate linear regression and logistic models were fitted to analyse associations between mean and peak PM2.5 exposure and clinical outcomes, stratified by smoking status.

Results

A 10 μg/m3 increase in mean PM2.5 exposure was associated with a 69% (95%CI: 11% to 158%) increase in odds of spirometry consistent with COPD amongst non-smokers and increased odds of chest tightness (odds ratio; OR 1.30, 95%CI 1.03 to 1.64) and chronic cough (OR 1.24, 95%CI 1.02 to 1.51) in the previous 12 months in all participants. For current smokers, increments in mean PM2.5 exposure were associated with higher odds of chronic cough in the preceding 12 months (OR 2.13, 95%CI 1.24 to 3.65).

Discussion

Almost four years after a six-week period of coal fire PM2.5 exposure, we identified a dose-response association between exposure and COPD in non-smokers. With climate change a likely contributor to increased risk of landscape fires, the findings will inform policy decisions during future sustained smoke events.

KEY MESSAGES

What is the key question?

Are there long-term impacts of a six-week mine fire event generating PM2.5 on COPD and related respiratory symptoms in adults?

What is the bottom line?

Almost 4 years after the mine fire, each 10 µg/m3 increase in PM2.5 exposure was associated with a 69% increase in odds of spirometry consistent with COPD amongst non-smokers, and a 30% increase in odds of chest tightness and 24% increase in odds of chronic cough amongst all participants. Amongst smokers, each 10 µg/m3 increase in PM2.5 was associated with a 113% increase in odds of chronic cough.

Why read on?

With the recent megafires in Australia and the United States exposing communities to smoke for weeks to months, evidence of the long-term health impacts of similar duration PM2.5 generating pollution events are needed to inform the public health response.
Quantification of different iron forms in the aceruloplasminemia brain to explore iron-related neurodegeneration
Authors: Vroegindeweij Lena H.P. , Bossoni Lucia , Boon Agnita J.W. , Wilson J.H. Paul , Bulk Marjolein , Huber Martina , Labra-Muñoz Jacqueline , Webb Andrew , van der Weerd Louise , Langendonk Janneke G.
Published: October 2020

Introduction

Aceruloplasminemia is an ultra-rare neurodegenerative disorder associated with massive brain iron accumulation. It is unknown which molecular forms of iron accumulate in the brain of patients with aceruloplasminemia. As the disease is associated with at least a fivefold increase in brain iron concentration compared to the healthy brain, it offers a unique model to study the role of iron in neurodegeneration and the molecular basis of iron-sensitive MRI contrast.

Methods

The iron-sensitive MRI metrics inhomogeneous transverse relaxation rate (R2*) and magnetic susceptibility obtained at 7T were combined with Electron Paramagnetic Resonance (EPR) and Superconducting Quantum Interference Device (SQUID) magnetometry to specify and quantify the different iron forms per gram wet-weight in a post-mortem aceruloplasminemia brain, with focus on the basal ganglia, thalamus, red nucleus, dentate nucleus, superior-and middle temporal gyrus and white matter. MRI, EPR and SQUID results that had been previously obtained from the temporal cortex of healthy controls were included for comparison.

Results

The brain iron pool in aceruloplasminemia consisted of EPR-detectable Fe3+ ions, magnetic Fe3+ embedded in the core of ferritin and hemosiderin (ferrihydrite-iron), and magnetic Fe3+ embedded in oxidized magnetite/maghemite minerals (maghemite-iron). Of all the studied iron pools, above 90% was made of ferrihydrite-iron, of which concentrations up to 1065 µg/g were detected in the red nucleus. Although deep gray matter structures in the aceruloplasminemia brain were three times richer in ferrihydrite-iron than the temporal cortex, ferrihydrite-iron in the temporal cortex of the patient with aceruloplasminemia was already six times more abundant compared to the healthy situation (162 µg/g vs. 27 µg/g). The concentration of Fe3+ ions and maghemite-iron were 1.7 times higher in the temporal cortex in aceruloplasminemia than in the control subjects. Of the two quantitative MRI metrics, R2* was the most illustrative of the pattern of iron accumulation and returned relaxation rates up to 0.49 ms-1, which were primarily driven by the abundance of ferrihydrite-iron. Maghemite-iron did not follow the spatial distribution of ferrihydrite-iron and did not significantly contribute to MRI contrast in most of the studied regions.

Conclusions

Even in extremely iron-loaded cases, iron-related neurodegeneration remains primarily associated with an increase in ferrihydrite-iron, with ferrihydrite-iron being the major determinant of iron-sensitive MRI contrast.
Linking microstructural integrity and motor cortex excitability in multiple sclerosis
Authors: Radetz Angela , Mladenova Kalina , Ciolac Dumitru , Gonzalez-Escamilla Gabriel , Fleischer Vinzenz , Ellwardt Erik , Krämer Julia , Bittner Stefan , Meuth Sven G. , Muthuraman Muthuraman , Groppa Sergiu
Published: October 2020

Motor skills are frequently impaired in multiple sclerosis (MS) patients following grey (GM) and white matter (WM) damage with cortical excitability abnormalities. We performed advanced diffusion imaging for neurite orientation dispersion and density modeling and diffusion tensor imaging within the motor system of 50 MS patients and 49 age-matched healthy controls. To assess excitability, we determined resting motor thresholds using non-invasive transcranial magnetic stimulation. A hierarchical regression model revealed that lower neurite density index (NDI), suggestive for axonal loss in the GM, predicted higher motor thresholds, i.e. reduced excitability in MS patients. Furthermore, lower NDI was indicative of decreased cognitive-motor performance. Interconnected motor WM tracts of patients were characterized by overlapping clusters of lowered fractional anisotropy and NDI, with NDI exclusively capturing a higher amount of abnormally appearing voxels. Our work outlines the potential of microstructure imaging using advanced biophysical models to forecast neurodegeneration and excitability alterations in neuroinflammation.
Impact of SARS-CoV-2 on Seasonal Respiratory Viruses: A Tale of Two Large Metropolitan Centers in the United States
Authors: Sherman Amy C. , Babiker Ahmed , Sieben Andrew J. , Pyden Alexander , Steinberg James , Kraft Colleen S. , Koelle Katia , Kanjilal Sanjat
Published: October 2020

To assess the impact of the SARS-CoV-2 pandemic on seasonal respiratory viruses, absolute case counts and viral reproductive rates from 2019-2020 were compared against previous seasons. Our findings suggest that the public health measures implemented to reduce SARS-CoV-2 transmission significantly reduced the transmission of other respiratory viruses.
Effective Deep Learning Approaches for Predicting COVID-19 Outcomes from Chest Computed Tomography Volumes
Authors: Trivedi Anusua , Ortiz Anthony , Desbiens Jocelyn , Robinson Caleb , Blazes Marian , Gupta Sunil , Dodhia Rahul , Bhatraju Pavan , Liles W. Conrad , Lee Aaron , Ferres Juan M. Lavista
Published: October 2020

The rapid evolution of the novel coronavirus SARS-CoV-2 pandemic has resulted in an urgent need for effective clinical tools to reduce transmission and manage severe illness. Numerous teams are quickly developing artificial intelligence approaches to these problems, including using deep learning to predict COVID-19 diagnosis and prognosis from computed tomography (CT) imaging data. In this work, we assess the value of aggregated chest CT data for COVID-19 prognosis compared to clinical metadata alone. We develop a novel patient-level algorithm to aggregate the chest CT volume into a 2D representation that can be easily integrated with clinical metadata to distinguish Novel Coronavirus Pneumonia (COVID-19+) from other cases of viral pneumonia and normal healthy chest CT volumes with state-of-the-art performance. Furthermore, we present a multitask model for joint segmentation of different classes of pulmonary lesions present in COVID-19 infected lungs that can outperform individual segmentation models for each task. We directly compare this multitask segmentation approach to combining feature-agnostic volumetric CT classification feature maps with clinical metadata for predicting mortality. These approaches enable the automated extraction of clinically relevant features from chest CT volumes for risk stratification of COVID-19+ patients.
Lessons from applied large-scale pooling of 133,816 SARS-CoV-2 RT-PCR tests
Authors: Barak Netta , Ben-Ami Roni , Sido Tal , Perri Amir , Shtoyer Aviad , Rivkin Mila , Licht Tamar , Peretz Ayelet , Magenheim Judith , Fogel Irit , Livneh Ayala , Daitch Yutti , Oiknine-Djian Esther , Benedek Gil , Dor Yuval , Wolf Dana G. , Yassour Moran ,   The Hebrew University-Hadassah COVID-19 diagnosis team
Published: October 2020

Pooling multiple swab samples prior to RNA extraction and RT-PCR analysis was proposed as a strategy to reduce costs and increase throughput of SARS-CoV-2 tests. However, reports on practical large-scale group testing for SARS-CoV-2 have been scant. Key open questions concern reduced sensitivity due to sample dilution; the rate of false positives; the actual efficiency (number of tests saved by pooling) and the impact of infection rate in the population on assay performance. Here we report analysis of 133,816 samples collected at April-September 2020, tested by pooling for the presence of SARS-CoV-2. We spared 76% of RNA extraction and RT-PCR tests, despite the reality of frequently changing prevalence rate (0.5%-6%). Surprisingly, we observed pooling efficiency and sensitivity that exceed theoretical predictions, which resulted from non-random distribution of positive samples in pools. Overall, the findings strongly support the use of pooling for efficient large high throughput SARS-CoV-2 testing.
Different mutations in SARS-CoV-2 associate with severe and mild outcome
Authors: Nagy Ádám , Pongor Sándor , Győrffy Balázs
Published: October 2020

Introduction

Genomic alterations in a viral genome can lead to either better or worse outcome and identifying these mutations is of utmost importance. Here, we correlated protein-level mutations in the SARS-CoV-2 virus to clinical outcome.

Methods

Mutations in viral sequences from the GISAID virus repository were evaluated by using “hCoV-19/Wuhan/WIV04/2019” as the reference. Patient outcomes were classified as mild disease, hospitalization and severe disease (death or documented treatment in an intensive-care unit). Chi-square test was applied to examine the association between each mutation and patient outcome. False discovery rate was computed to correct for multiple hypothesis testing and results passing a FDR cutoff of 5% were accepted as significant.

Result

Mutations were mapped to amino acid changes for 2,120 non-silent mutations. Mutations correlated to mild outcome were located in the ORF8, NSP6, ORF3a, NSP4, and in the nucleocapsid phosphoprotein N. Mutations associated with inferior outcome were located in the surface (S) glycoprotein, in the RNA dependent RNA polymerase, in the 3’-to5’ exonuclease, in ORF3a, NSP2 and N. Mutations leading to severe outcome with low prevalence were found in the surface (S) glycoprotein and in NSP7. Five out of 17 of the most significant mutations mapped onto a 10 amino acid long phosphorylated stretch of N indicating that in spite of obvious sampling restrictions the approach can find functionally relevant sites in the viral genome.

Conclusions

We demonstrate that mutations in the viral genes may have a direct correlation to clinical outcome. Our results help to quickly identify SARS-CoV-2 infections harboring mutations related to severe outcome.
Impact of the COVID-19 pandemic on Suicide and Self Harm among Patients Presenting to the Emergency Department of a Teaching Hospital in Nepal
Authors: Shrestha Roshana , Siwakoti Shisir , Singh Saumya , Shrestha Anmol Purna
Published: October 2020

Background

The COVID-19 pandemic is a global challenge that is not just limited to the physical consequences but also a significant degree of a mental health crisis. Self-harm (SH) and suicide are its extreme effects. The aim of this study was to provide an overview of the impact of the COVID-19 pandemic on the occurrence and clinical profile of suicide and SH in our ED.

Methods

This is a cross-sectional observational study conducted in the ED of a tertiary care center. Records of all fatal and nonfatal SH patients presenting to the ED during the lockdown period (March 24-June 23, 2020; Period1), matching periods in the previous year (March 24-June 23,2019; Period 2) and 3 months period prior (December 24 2019-March 23, 2020; Period 3) was included by searching the electronic medical record (EMR) system. The prevalence and the clinical profile of the patients were compared between these three periods.

Results

A total of 125 (periods 1=55, 2=38, and 3=32) suicide and SH cases were analyzed. The cases of suicide/SH had increased by 44% and 71.9% during the lockdown period in comparison to the period 2 and 3. Organophosphate poisoning was the most common mode. Females were predominant in all three periods with a mean age of 32 (95%CI: 29.3-34.7). There was a significant delay in arrival of the patients in period 1 (p-value=0.045) with increased hospital admission (p-value =0.009) and in-hospital mortality (18.2% vs 2.6 % and 3.1%) (p-value=.001).

Conclusion

We found an increase in patients presenting with suicide and SH in our ED during the pandemic which is likely to reflect an increased prevalence of mental illness in the community. We hope that the result will prime all mental health care stakeholders to initiate mental health screening and intervention for the vulnerable population during this period of crisis.
Concurrent comorbidities substantially alter long-term health behaviours and outcomes of headache patients
Authors: Nash Anthony , Goodday Sarah , Liu Qiang , Fuller Alice , Bankhead Clare , Webber Caleb , Nevado-Holgado Alejo J. , Cader M. Zameel
Published: October 2020

Objectives

To investigate factors affecting the long-term health behaviours and outcomes of headache patients and to design a risk-stratification tool.

Methods

A population based observational-longitudinal cohort study using primary care electronic healthcare records from the UK Clinical Practice Research Datalink. 550,103 participants with a headache or migraine diagnosis of which 170,336 patients were identified as having recurrent headache-related events. Univariate and multivariable survival analysis was performed to determine factors influencing remission and a neural network classifier was developed.

Results

There were almost twice as many female patients (352,330) as males (197,802). The median age at which a patient first saw their GP in males was 38 years, and in females was 37 years. Whilst age, gender and social deprivation significantly influenced the likelihood of seeing a GP, these factors had little effect on likelihood of remission from a period of recurrent headache-related events. In contrast, a comorbidity during the recurrent headache period reduced the risk of remission and increased median survival time from approximately 400-days up 1600. Increasing numbers of comorbidities progressively reduced the hazard risks for remission. The prediction models on remission within two and five years, demonstrated high precision and recall, with an F1 score of 0.795 and 0.887, respectively.

Interpretation

Headache patients who suffer comorbidities have a substantively reduced likelihood of remission, highlighting an opportunity to considerably improve health outcomes in recurrent headache patients through addressing multi-morbidity more effectively. The prediction model could be used to help stratify patients most at risk of poor long-term outcomes.
Evaluation of applicability of the online version of HADS-D for depression phenotype screening in the general population
Authors: Kibitov AA , Rakitko AS , Kasyanov ED , Rukavishnikov GV , Kozlova KA , Ilinsky VV , Neznanov NG , Mazo GE , Kibitov AO
Published: October 2020

One of the most promising areas of research into the biological underpinnings of depression is genetic studies. However, the absence of generally accepted phenotyping methods leads to the difficulties in generalizing their results due to the heterogeneity of the samples. Thus, the development of a reliable and convenient phenotyping method that allows large sample sizes to be included in studies remains a top priority for the further development of genetic studies of depression.

The aim of this study was to evaluate the applicability of the online version of the depression subscale of Hospital Anxiety and Depression Scale (HADS-D) for depression phenotype screening in the general population. Using online HADS-D we performed screening of depressive symptoms and compared results with known population patterns of depression.

We conducted an online survey of 2610 Russian-speaking respondents over the age of 18. The overall HADS-D score was higher in women (p=0.003), in individuals under 30 y.o compared to participants over 42 y.o. (p=0.004) and in individuals reporting cardiovascular diseases (CVD) symptoms (p<0.0001).

Linear regression showed that the presence of CVD leads to higher HADS-D scores (p<0.001), male gender (p=0.002) and older age (p<0.001) led to lower scores. Logistic regression showed that CVD increases the risk of having depression symptoms by HADS-D (p=0.033, OR=1.29), older age (p=0.015, OR=0.87) and male sex (as a trend, p=0.052, OR=0.80) decrease this risk.

These results are consistent with the known data on the association of sex, age, and the presence of CVD with the prevalence of depression. The online version of HADS-D, given the ease of its usage, can be regarded as an effective tool for phenotyping depression in the general population.