Publications by authors named "Amit Patel"

627 Publications

Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia.

ERJ Open Res 2021 Jan 8;7(1). Epub 2021 Feb 8.

Centre for Human and Applied Physiological Sciences, King's College London, London, UK.

Background: A standardised approach to assessing COVID-19 survivors has not been established, largely due to the paucity of data on medium- and long-term sequelae. Interval chest radiography is recommended following community-acquired pneumonia; however, its utility in monitoring recovery from COVID-19 pneumonia remains unclear.

Methods: This was a prospective single-centre observational cohort study. Patients hospitalised with severe COVID-19 pneumonia (admission duration ≥48 h and oxygen requirement ≥40% or critical care admission) underwent face-to-face assessment at 4-6 weeks post-discharge. The primary outcome was radiological resolution of COVID-19 pneumonitis (Radiographic Assessment of Lung Oedema score <5). Secondary outcomes included clinical outcomes, symptom questionnaires, mental health screening (Trauma Screening Questionnaire, seven-item Generalised Anxiety Disorder assessment and nine-item Patient Health Questionnaire) and physiological testing (4-m gait speed (4MGS) and 1-min Sit-to-Stand (STS) tests).

Results: 119 patients were assessed between June 3, 2020 and July 2, 2020 at median (interquartile range (IQR)) 61 (51-67) days post-discharge: mean±sd age 58.7±14.4 years, median (IQR) body mass index 30.0 (25.9-35.2) kg·m, 62% male and 70% ethnic minority. Despite radiographic resolution of pulmonary infiltrates in 87%, modified Medical Research Council Dyspnoea (breathlessness) scale grades were above pre-COVID-19 baseline in 44%, and patients reported persistent fatigue (68%), sleep disturbance (57%) and breathlessness (32%). Screening thresholds were breached for post-traumatic stress disorder (25%), anxiety (22%) and depression (18%). 4MGS was slow (<0.8 m·s) in 38% and 35% desaturated by ≥4% during the STS test. Of 56 thoracic computed tomography scans performed, 75% demonstrated COVID-19-related interstitial and/or airways disease.

Conclusions: Persistent symptoms, adverse mental health outcomes and physiological impairment are common 2 months after severe COVID-19 pneumonia. Follow-up chest radiography is a poor marker of recovery; therefore, holistic face-to-face assessment is recommended to facilitate early recognition and management of post-COVID-19 sequelae.
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http://dx.doi.org/10.1183/23120541.00655-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585700PMC
January 2021

Monocytes, Macrophages, Dendritic Cells and Neutrophils: an update on lifespan kinetics in health and disease.

Immunology 2021 Feb 8. Epub 2021 Feb 8.

Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel.

Phagocytes form a family of immune cells that play a crucial role in tissue maintenance and help orchestrate the immune response. This family of cells can be separated by their nuclear morphology into mononuclear and polymorphonuclear phagocytes. The generation of these cells in the bone marrow, to the blood and finally into tissues is a tightly regulated process. Ensuring the adequate production of these cells and their timely removal, is key for both the initiation and resolution of inflammation. Insight into the kinetic profiles of innate myeloid cells during steady state and pathology will permit the rational development of therapies to boost the production of these cells in times of need or reduce them when detrimental.
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http://dx.doi.org/10.1111/imm.13320DOI Listing
February 2021

Response: AGA Clinical Practice Guideline on the Gastrointestinal Evaluation of Iron Deficiency Anemia.

Gastroenterology 2021 Feb 2. Epub 2021 Feb 2.

Division of Gastroenterology, Duke University and the Durham VA Medical Center, Durham, North Carolina.

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http://dx.doi.org/10.1053/j.gastro.2021.01.224DOI Listing
February 2021

Quantification of Scopoletin from Roots of Argyreia Speciosa (Linn. F) Sweet Using HPLC through the Concept of Design of Experiment.

J AOAC Int 2021 Jan 30. Epub 2021 Jan 30.

Department of Pharmaceutics and Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa-, 388421, Anand, Gujarat, India.

Background: Roots of Argyreia speciosa (Linn. F) Sweet (family: Convolvulaceae) are used in Ayurveda to treat male reproductive and nervous system disorders.

Objective: Isolation of scopoletin from the roots of Argyreia speciosa, development and validation of an analytical method using HPLC for the quantification of scopoletin from the root powder of Argyreia speciosa.

Method: Scopoletin was isolated from chloroform fraction prepared from hydrolyzed methanolic extract and identified using spectral studies. A reverse-phase HPLC based analytical method was developed and optimized using the DoE approach to estimate scopoletin from the roots of Argyreia speciosa. Scopoletin was separated and quantified using HPLC containing C18 column and a PDA detector. The optimized mobile phase was methanol: water (pH∼3.2) [25: 75, %v/v].

Results: The Box-Behnken design was used to optimize chromatographic parameters and the extraction procedure. The validation studies showed a linear relationship (r2=0.998) in the range of 1-40 µg/ml. The limit of Detection and Limit of Quantification were found to be 0.28 µg/ml and 0.84 µg/ml, respectively and the recovery values were found between 91.94 to 97.86%. The developed analytical method was found robust too. The amount of scopoletin was estimated to be 0.024 ± 0.0016%w/w from dried root powder.

Conclusion: The recorded chromatogram and amount of scopoletin determined would serve as one of the standardization parameters to access the quality of raw material containing Argyreia speciosa.

Highlights: Developed analytical method may be adopted as a part of the standardization procedure for Argyreia speciosa in the quality control laboratory.
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http://dx.doi.org/10.1093/jaoacint/qsab013DOI Listing
January 2021

Fast Strain-Encoded Cardiac Magnetic Resonance for Diagnostic Classification and Risk Stratification of Heart Failure Patients.

JACC Cardiovasc Imaging 2021 Jan 4. Epub 2021 Jan 4.

Department of Cardiology, Marien Hospital Hamburg, Hamburg, Germany.

Objectives: The purpose of this study was to compare the ability of fast-strain encoded magnetic resonance (fast-SENC) cardiac magnetic resonance (CMR) to classify and risk stratify all-comer patients with different stages of chronic heart failure (Stages of heart failure A to D) based on American College of Cardiology/American Heart Association guidelines with standard clinical and CMR imaging data.

Background: Heart failure is a major cause of morbidity and mortality, resulting in millions of deaths and hospitalizations annually.

Methods: The study population consisted of 1,169 consecutive patients between September 2017 and February 2019 who underwent CMR for clinical reasons, and 61 healthy volunteers. In addition, clinical follow-up was performed in Stages A and B patients after 1.9 ± 0.4 years. Wall motion score and late gadolinium enhancement score indexes, left ventricular (LV) ejection fraction, and global circumferential and longitudinal strain based on fast-SENC acquisitions, were calculated in all subjects. The percentage of myocardial segments with strain ≤-17% (% normal myocardium) was determined in all subjects.

Results: LV ejection fraction, global circumferential and longitudinal strain, and % normal myocardium significantly decreased with increasing heart failure stages (p < 0.001 for all by analysis of variance). By multivariable analysis, % normal myocardium remained an independent predictor of heart failure stages, exhibiting closer association than LV ejection fraction (r = 0.76 vs. r = 0.30; p < 0.001). Importantly, 149 of 399 (37%) with Stage A were reclassified to Stage B, that is, as having subclinical LV dysfunction based on % normal myocardium <80%. Such patients exhibited significantly higher rates of all-cause mortality and hospital stay due to heart failure during follow-up, compared with patients with % normal myocardium ≥80% (χ = 6.9; p = 0.03).

Conclusions: % normal myocardium, determined by fast-SENC, enables improved identification of asymptomatic patients with subclinical LV dysfunction compared with LV ejection fraction and risk stratification of patients with so far asymptomatic heart failure. The identification of such presumably healthy patients at high risk for heart failure-related outcomes may bear important medical implications.
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http://dx.doi.org/10.1016/j.jcmg.2020.10.024DOI Listing
January 2021

Characterization of a highly stable mixed-mode reversed-phase/weak anion-exchange stationary phase based on hybrid organic/inorganic particles.

J Sep Sci 2020 Dec 22. Epub 2020 Dec 22.

Waters Corporation, Milford, Massachusetts, USA.

We have characterized Atlantis ethylene-bridged hybrid C anion-exchange, a mixed-mode reversed-phase/weak anion-exchange stationary phase designed to give greater retention for anions (e.g., ionized acids) compared to conventional reversed-phase materials. The retention and selectivity of this stationary phase were compared to that of three benchmark materials, using a mixture of six polar compounds that includes an acid, two bases, and three neutrals. The compatibility of the ethylene-bridged hybrid C anion-exchange material with 100% aqueous mobile phases was also evaluated. We investigated the batch-to-batch reproducibility of the ethylene-bridged hybrid C anion-exchange stationary phase for 27 batches across three different particle sizes (1.7, 2.5, and 5 μm) and found it to be comparable to that of one of the most reproducible C stationary phases. We also characterized the acid and base stability of the ethylene-bridged hybrid C anion-exchange stationary phase and the results show it to be usable over a wide pH range, from 2 to 10. The extended upper pH limit relative to silica-based reversed-phase/weak anion-exchange materials is enabled by the use of ethylene-bridged hybrid organic/inorganic particles. The improved base stability allows Atlantis ethylene-bridged hybrid C anion-exchange to be used with a wider range of mobile phase pH values, opening up a greater range of selectivity options.
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http://dx.doi.org/10.1002/jssc.202001136DOI Listing
December 2020

Inhibition of GCK-IV kinases dissociates cell death and axon regeneration in CNS neurons.

Proc Natl Acad Sci U S A 2020 12 14;117(52):33597-33607. Epub 2020 Dec 14.

Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093;

Axon injury is a hallmark of many neurodegenerative diseases, often resulting in neuronal cell death and functional impairment. Dual leucine zipper kinase (DLK) has emerged as a key mediator of this process. However, while DLK inhibition is robustly protective in a wide range of neurodegenerative disease models, it also inhibits axonal regeneration. Indeed, there are no genetic perturbations that are known to both improve long-term survival and promote regeneration. To identify such a neuroprotective target, we conducted a set of complementary high-throughput screens using a protein kinase inhibitor library in human stem cell-derived retinal ganglion cells (hRGCs). Overlapping compounds that promoted both neuroprotection and neurite outgrowth were bioinformatically deconvoluted to identify specific kinases that regulated neuronal death and axon regeneration. This work identified the role of germinal cell kinase four (GCK-IV) kinases in cell death and additionally revealed their unexpected activity in suppressing axon regeneration. Using an adeno-associated virus (AAV) approach, coupled with genome editing, we validated that GCK-IV kinase knockout improves neuronal survival, comparable to that of DLK knockout, while simultaneously promoting axon regeneration. Finally, we also found that GCK-IV kinase inhibition also prevented the attrition of RGCs in developing retinal organoid cultures without compromising axon outgrowth, addressing a major issue in the field of stem cell-derived retinas. Together, these results demonstrate a role for the GCK-IV kinases in dissociating the cell death and axonal outgrowth in neurons and their druggability provides for therapeutic options for neurodegenerative diseases.
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http://dx.doi.org/10.1073/pnas.2004683117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7777023PMC
December 2020

Prognostic value of cardiac magnetic resonance septal late gadolinium enhancement patterns for periaortic ventricular tachycardia ablation: Heterogeneity of the anteroseptal substrate in nonischemic cardiomyopathy.

Heart Rhythm 2020 Dec 8. Epub 2020 Dec 8.

Center for Arrhythmia Care, University of Chicago Medicine, Pritzker School of Medicine, Chicago, Illinois. Electronic address:

Background: Ventricular tachycardia (VT) from the anteroseptal subtype of nonischemic cardiomyopathy has a high probability of recurrence after catheter ablation.

Objective: The purpose of this study was to determine the predictive value of septal scar patterns by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) on ablation outcomes in patients with VT arising from an anteroseptal substrate.

Methods: Patients with periaortic VT arising from an anteroseptal substrate with preprocedural wideband LGE-CMR were divided into 2 groups by the degree of longitudinal septal LGE extension as full-length septal (≥80% anteroposterior length) or partial septal (<80% anteroposterior length). Septal LGE volumes were quantified in those with and without VT recurrence.

Results: Among 234 patients referred for scar-related VT ablation between 2017 and 2020, 25 patients (92% male; age 64 ± 8 years) and a total of 108 VTs were analyzed. A greater number of VT morphologies were induced in patients with full-length septal LGE compared to partial septal LGE (median [interquartile range]: 5 [3-9] vs 2 [1-4]; P = .005). Patients with VT recurrence had larger septal LGE volumes compared to those without recurrence (11.4 mL [8.8-13.9] vs 4.2 mL [0-9.5]; P = .012). At median follow-up of 16 months (5-22), overall freedom from VT recurrence was 52% and significantly higher in patients with partial septal LGE than in those with full-length septal LGE (80% vs 20%; P = .005).

Conclusion: VT originating from an anteroseptal substrate is associated with heterogeneous patterns and extent of CMR septal scar. Preprocedural imaging may substratify this challenging patient population for the propensity for multiple induced VT morphologies and recurrence after catheter ablation.
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http://dx.doi.org/10.1016/j.hrthm.2020.12.003DOI Listing
December 2020

Bio-extract amalgamated sodium alginate-cellulose nanofibres based 3D-sponges with interpenetrating BioPU coating as potential wound care scaffolds.

Mater Sci Eng C Mater Biol Appl 2021 Jan 11;118:111348. Epub 2020 Aug 11.

Indian Institute of Technology Roorkee, Department of Polymer and Process Engineering, Saharanpur Campus, Saharanpur 247001, U.P., India. Electronic address:

In this work, sodium alginate (SA) based "all-natural" composite bio-sponges were designed for potential application as wound care scaffold. The composite bio-sponges were developed from the aqueous amalgamation of SA and cellulose nanofibres (CNFs) in bio-extracts like Rice water (Rw) and Giloy extract (Ge). These sponges were modified by employing a simple coating strategy using vegetable oil-based bio-polyurethane (BioPU) to tailor their physicochemical and biological properties so as to match the specific requirements of a wound care scaffold. Bio-sponges with shared interpenetrating polymeric network structures were attained at optimized BioPU coating formulation. The interpenetration of BioPU chains within the sponge construct resulted in the formation of numerous micro-networks in the interconnected microporous structure of sponges (porosity ≥75%). The coated sponge showed a superior mechanical strength (compressive strength ~3.8 MPa, compressive modulus ~35 MPa) with appreciable flexibility and recoverability under repeated compressive loading-unloading cycles. A tunable degradation behaviour was achieved by varying BioPU coating concentrations owing to the different degree of polymer chain entanglement within the sponge construct. The physical entanglement of BioPU chains with core structural components of sponge improved their structural stability by suppressing their full fragmentation in water-based medium without affecting its swelling behaviour (swelling ratio > 1000%). The coated sponge surface has provided a suitable moist-adherent physical environment to support the adhesion and growth of skin cells (HaCaT cells). The MTT (3-(4,5-dimethyl thiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and hemolytic assay revealed the non-toxic and biocompatible nature of coated sponges in vitro. Moreover, no signs of skin erythema or edema were observed during in vivo dermal irritation and corrosion test performed on the skin of Sprague Dawley (SD) rats. Our initial observations revealed the credibility of these sponges as functional wound care scaffolds as well as its diverse potential as a suitable substrate for various tissue engineering applications.
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http://dx.doi.org/10.1016/j.msec.2020.111348DOI Listing
January 2021

The Clinical Utility of Provocative Maneuvers at Esophageal High-resolution Manometry (HRM).

J Clin Gastroenterol 2021 Feb;55(2):95-102

Division of Gastroenterology, Duke University School of Medicine.

Esophageal high-resolution manometry (HRM) assesses esophageal motor function and is indicated both for evaluation of esophageal symptoms and before antireflux interventions. HRM studies are interpreted and esophageal motor diagnoses made according to the Chicago Classification, version 3.0 algorithm, which is based on ten 5 mL supine water swallows. However, this practice of single liquid swallows performed in the supine position does not reflect typical "real-life" swallowing, and may not reproduce the patient's presenting symptoms. Therefore, provocative maneuvers at HRM-beyond these 10 standard swallows-can afford additional insights into esophageal motor function with clinically significant implications, and represent areas of exciting investigation and innovation. Accordingly, the 2020 American College of Gastroenterology Guidelines on Esophageal Physiologic Testing conditionally recommend their inclusion in the HRM protocol. In this clinical review, we discuss the supporting data for and clinical utility of provocative maneuvers at HRM that include changes in body position or accessories (upright swallows, "bridge" position, straight leg raise, abdominal compression), bolus consistency (solid swallows, test meals, postprandial high-resolution impedance manometry), bolus frequency (multiple rapid swallows), the volume of bolus (rapid drink challenge/multiple water swallows), and the use of pharmacological agents.
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http://dx.doi.org/10.1097/MCG.0000000000001466DOI Listing
February 2021

Developing a coordinate-based strategy to support cognitive targeted prostate biopsies and correlative spatial-histopathological outcome analysis.

Asian J Androl 2020 Nov 24. Epub 2020 Nov 24.

Department of Urology, Queen Elizabeth University Hospital, 1345 Govan Rd, Glasgow G51 4TF, UK.

Lack of investment for magnetic resonance (MR) fusion systems is an obstacle to deliver targeted prostate biopsies within the prostate cancer diagnostic pathway. We developed a coordinate-based method to support cognitive targeted prostate biopsies and then performed an audit on cancer detection and the location of lesions. In each patient, the prostate is considered as two separate hemiprostates, and each hemiprostate is divided into 4 × 4 × 4 units. Each unit is therefore defined by a three-dimensional coordinate. We prospectively applied our coordinates approach to target 106 prostatic lesions in 93 men. Among 45 (of 106; 42.5%) lesions positive for cancer, 27 lesions (60.0%) harbored clinically significant disease. PSA density was significantly higher in patients with proven cancer (median: 0.264 ng ml) when compared to the noncancer group (median: 0.145 ng ml; P = 0.003, Wilcoxon rank-sum test). Lesions with Prostate Imaging-Reporting and Data System (PIRADS) score of 5 were found to have a cancer incidence of 65.2%, while PIRADS 4 and 3 lesions have a lower risk of cancer detection, as expected, at 37.3% and 31.3%, respectively. The probability of a lesion being cancerous in our series significantly decreases as we go from the "apex-to-base" dimension (odds ratio [OR]: 2.62, 95% confidence interval [CI]: 1.55-4.44, P = 0.00034). Our analysis also indicates that the probability of cancer decreases as the prostate volume increases (OR: 1.03, 95% CI: 1.01-1.05, P = 0.00327). Based on this feasibility study, the use of coordinates to guide cognitive targeted prostate biopsies warrants future validation study in additional centers.
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http://dx.doi.org/10.4103/aja.aja_49_20DOI Listing
November 2020

Informant-based screening tools for diagnosis of dementia, an overview of systematic reviews of test accuracy studies protocol.

Syst Rev 2020 11 26;9(1):271. Epub 2020 Nov 26.

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.

Background: Robust diagnosis of dementia requires an understanding of the accuracy of the available diagnostic tests. Informant questionnaires are frequently used to assess for dementia in clinical practice. Recent systematic reviews have sought to establish the diagnostic test accuracy of various dementia informant screening tools. However, most reviews to date have focused on a single diagnostic tool and this does not address which tool is 'best'. A key aim of the overview of systematic reviews is to present a disparate evidence base in a single, easy to access platform.

Methods: We will conduct an overview of systematic reviews in which we 'review the systematic reviews' of diagnostic test accuracy studies evaluating informant questionnaires for dementia. As an overview of systematic reviews of test accuracy is a relatively novel approach, we will use this review to explore methods for visual representation of complex data, for highlighting evidence gaps and for indirect comparative analyses. We will create a list of informant tools by consulting with dementia experts. We will search 6 databases (EMBASE (OVID); Health and Psychosocial Instruments (OVID); Medline (OVID); CINAHL (EBSCO); PSYCHinfo (EBSCO) and the PROSPERO registry of review protocols) to identify systematic reviews that describe the diagnostic test accuracy of informant questionnaires for dementia. We will assess review quality using the AMSTAR-2 (Assessment of Multiple Systematic Reviews) and assess reporting quality using PRISMA-DTA (Preferred Reporting Items for Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies) checklists. We will collate the identified reviews to create an 'evidence map' that highlights where evidence does and does not exist in relation to informant questionnaires. We will pool sensitivity and specificity data via meta-analysis to generate a diagnostic test accuracy summary statistic for each informant questionnaire. If data allow, we will perform a statistical comparison of the diagnostic test accuracy of each informant questionnaire using a network approach.

Discussion: Our overview of systematic reviews will provide a concise summary of the diagnostic test accuracy of informant tools and highlight areas where evidence is currently lacking in this regard. It will also apply network meta-analysis techniques to a new area.
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http://dx.doi.org/10.1186/s13643-020-01530-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694897PMC
November 2020

Prevalence of newly diagnosed sarcoidosis in patients with ventricular arrhythmias: a cardiac magnetic resonance and 18F-FDG cardiac PET study.

Int J Cardiovasc Imaging 2020 Nov 22. Epub 2020 Nov 22.

Department of Medicine, Section of Cardiology, University of Chicago Medicine, 5758 S. Maryland Avenue, MC 9067, Chicago, IL, 60637, USA.

Cardiac sarcoidosis (CS) is known to be associated with ventricular tachycardia (VT); however, most investigations to date have focused on patients with known extra-cardiac sarcoidosis. The presence of CS is typically evaluated using 18F-fluorodeoxyglucose (18F-FDG) uptake on cardiac positron emission tomography (PET) or late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). In this study, we sought to determine the prevalence of primary CS and the relationship between myocardial 18F-FDG uptake and LGE in patients with VT without known sarcoidosis. We retrospectively identified 67 patients without known sarcoidosis or active ischemic heart disease (i.e. significant ischemic disease that had not been previously revascularized) referred for both CMR and PET for evaluation of VT. Standard cine- and LGE- CMR and cardiac PET protocols were used. Myocardial LGE was defined as signal intensity > 5 SDs above the mean signal intensity of normal myocardium. Cardiac PET images were considered positive if there was focal myocardial 18F-FDG uptake having greater activity than the left ventricular blood pool. 45 patients (67%) had LGE, while only 4 (6%) had myocardial FDG uptake. Nine percent of patients with LGE had FDG-uptake while none without LGE did, and 10% of the cohort had indeterminate FDG uptake presumably from poor dietary preparation. Of those with both FDG uptake and LGE, 3/4 ultimately received a clinical diagnosis of CS. 4.5% of patients without previously known sarcoidosis or active ischemic heart disease presenting with VT have newly diagnosed CS. Detection of CS can be increased using a CMR first approach followed by cardiac PET for patients with non-ischemic LGE.
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http://dx.doi.org/10.1007/s10554-020-02090-2DOI Listing
November 2020

Provision of holistic care after severe COVID-19 pneumonia: anticipating clinical need and managing resources.

Lancet Respir Med 2020 12 13;8(12):1175-1176. Epub 2020 Nov 13.

Centre for Human and Applied Physiological Sciences, King's College London, London WC2R 2LS, UK; Department of Respiratory Medicine, King's College Hospital NHS Foundation Trust, London, UK. Electronic address:

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http://dx.doi.org/10.1016/S2213-2600(20)30529-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834100PMC
December 2020

Stress CMR in patients with obesity: insights from the Stress CMR Perfusion Imaging in the United States (SPINS) registry.

Eur Heart J Cardiovasc Imaging 2020 Nov 9. Epub 2020 Nov 9.

Noninvasive Cardiovascular Imaging Section, Cardiovascular Division of Department of Medicine and Department of Radiology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Aims: Non-invasive assessment and risk stratification of coronary artery disease in patients with large body habitus is challenging. We aim to examine whether body mass index (BMI) modifies the prognostic value and diagnostic utility of stress cardiac magnetic resonance imaging (CMR) in a multicentre registry.

Methods And Results: The SPINS Registry enrolled consecutive intermediate-risk patients who presented with a clinical indication for stress CMR in the USA between 2008 and 2013. Baseline demographic data including BMI, CMR indices, and ratings of study quality were collected. Primary outcome was defined by a composite of cardiovascular death and non-fatal myocardial infarction. Of the 2345 patients with available BMI included in the SPINS cohort, 1177 (50%) met criteria for obesity (BMI ≥ 30) with 531 (23%) at or above Class 2 obesity (BMI ≥ 35). In all BMI categories, >95% of studies were of diagnostic quality for cine, perfusion, and late gadolinium enhancement (LGE) sequences. At a median follow-up of 5.4 years, those without ischaemia and LGE experienced a low annual rate of hard events (<1%), across all BMI strata. In patients with obesity, both ischaemia [hazard ratio (HR): 2.14; 95% confidence interval (CI): 1.30-3.50; P = 0.003] and LGE (HR: 3.09; 95% CI: 1.83-5.22; P < 0.001) maintained strong adjusted association with the primary outcome in a multivariable Cox regression model. Downstream referral rates to coronary angiography, revascularization, and cost of care spent on ischaemia testing did not significantly differ within the BMI categories.

Conclusion: In this large multicentre registry, elevated BMI did not negatively impact the diagnostic quality and the effectiveness of risk stratification of patients referred for stress CMR.
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http://dx.doi.org/10.1093/ehjci/jeaa281DOI Listing
November 2020

Recommendations for Follow-up Colonoscopy After Polypectomy.

JAMA 2020 Nov 6. Epub 2020 Nov 6.

Division of Gastroenterology, Duke University School of Medicine, Durham, North Carolina.

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http://dx.doi.org/10.1001/jama.2020.15001DOI Listing
November 2020

Artificial intelligence automates and augments baseline impedance measurements from pH-impedance studies in gastroesophageal reflux disease.

J Gastroenterol 2021 Jan 5;56(1):34-41. Epub 2020 Nov 5.

Division of Gastroenterology, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8124, Saint Louis, MO, 63110, USA.

Background: Artificial intelligence (AI) has potential to streamline interpretation of pH-impedance studies. In this exploratory observational cohort study, we determined feasibility of automated AI extraction of baseline impedance (AIBI) and evaluated clinical value of novel AI metrics.

Methods: pH-impedance data from a convenience sample of symptomatic patients studied off (n = 117, 53.1 ± 1.2 years, 66% F) and on (n = 93, 53.8 ± 1.3 years, 74% F) anti-secretory therapy and from asymptomatic volunteers (n = 115, 29.3 ± 0.8 years, 47% F) were uploaded into dedicated prototypical AI software designed to automatically extract AIBI. Acid exposure time (AET) and manually extracted mean nocturnal baseline impedance (MNBI) were compared to corresponding total, upright, and recumbent AIBI and upright:recumbent AIBI ratio. AI metrics were compared to AET and MNBI in predicting  ≥ 50% symptom improvement in GERD patients.

Results: Recumbent, but not upright AIBI, correlated with MNBI. Upright:recumbent AIBI ratio was higher when AET  > 6% (median 1.18, IQR 1.0-1.5), compared to  < 4% (0.95, IQR 0.84-1.1), 4-6% (0.89, IQR 0.72-0.98), and controls (0.93, IQR 0.80-1.09, p ≤ 0.04). While MNBI, total AIBI, and the AIBI ratio off PPI were significantly different between those with and without symptom improvement (p < 0.05 for each comparison), only AIBI ratio segregated management responders from other cohorts. On ROC analysis, off therapy AIBI ratio outperformed AET in predicting GERD symptom improvement when AET was  > 6% (AUC 0.766 vs. 0.606) and 4-6% (AUC 0.563 vs. 0.516) and outperformed MNBI overall (AUC 0.661 vs. 0.313).

Conclusions: BI calculation can be automated using AI. Novel AI metrics show potential in predicting GERD treatment outcome.
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http://dx.doi.org/10.1007/s00535-020-01743-2DOI Listing
January 2021

Guar Gum-Based Floating Microspheres of Repaglinide Using 3 Factorial Design: Fabrication, Optimization, Characterization, and Buoyancy Behavior in Albino Rats.

Assay Drug Dev Technol 2020 Oct 22. Epub 2020 Oct 22.

Department of Pharmacy, Ashoka Institute of Technology and Management, Varanasi, Uttar Pradesh, India.

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http://dx.doi.org/10.1089/adt.2020.1006DOI Listing
October 2020

Validation of non-contrast multiple overlapping thin-slab 4D-flow cardiac magnetic resonance imaging.

Magn Reson Imaging 2020 12 6;74:223-231. Epub 2020 Oct 6.

Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.

Background: Cardiac magnetic resonance (CMR) flow quantification is typically performed using 2D phase-contrast (PC) imaging of a plane perpendicular to flow. 3D-PC imaging (4D-flow) allows offline quantification anywhere in a thick slab, but is often limited by suboptimal signal, potentially alleviated by contrast enhancement. We developed a non-contrast 4D-flow sequence, which acquires multiple overlapping thin slabs (MOTS) to minimize signal loss, and hypothesized that it could improve image quality, diagnostic accuracy, and aortic flow measurements compared to non-contrast single-slab approach.

Methods: We prospectively studied 20 patients referred for transesophageal echocardiography (TEE), who underwent CMR (GE, 3 T). 2D-PC images of the aortic valve and three 4D-flow datasets covering the heart were acquired, including single-slab, pre- and post-contrast, and non-contrast MOTS. Each 4D-flow dataset was interpreted blindly for ≥moderate valve disease and compared to TEE. Flow visualization through each valve was scored (0 to 4), and aortic-valve flow measured on each 4D-flow dataset and compared to 2D-PC reference.

Results: Diagnostic quality visualization was achieved with the pre- and post-contrast 4D-flow acquisitions in 25% and 100% valves, respectively (scores 0.9 ± 1.1 and 3.8 ± 0.5), and in 58% with the non-contrast MOTS (1.6 ± 1.1). Accuracy of detection of valve disease was 75%, 92% and 82%, respectively. Aortic flow measurements were possible in 53%, 95% and in 89% patients, respectively. The correlation between pre-contrast single-slab measurements and 2D-PC reference was weak (r = 0.21), but improved with both contrast enhancement (r = 0.71) and with MOTS (r = 0.67).

Conclusions: Although non-contrast MOTS 4D-flow improves valve function visualization and diagnostic accuracy, a significant proportion of valves cannot be accurately assessed. However, aortic flow measurements using non-contrast MOTS is feasible and reaches similar accuracy to that of contrast-enhanced 4D-flow.
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http://dx.doi.org/10.1016/j.mri.2020.10.002DOI Listing
December 2020

Effects of residential mobility and migration on standards of living in Dar es Salaam, Tanzania: A life-course approach.

PLoS One 2020 29;15(9):e0239735. Epub 2020 Sep 29.

Department of Public Policy and Public Affairs, McCormack Graduate School of Policy and Global Studies, University of Massachusetts, Boston, MA, United States of America.

Rural-to-urban migration and intra-urban residential mobility often lead to improved living conditions. However, it is not clear if this is true for all, especially in cities in developing countries, where inequalities persist and upward mobility remains elusive for marginalized populations. We investigate the effects of intra-urban residential mobility and rural-to-urban migration on standards of living in Dar es Salaam, Tanzania. We examine the entire residential history of individuals and assess temporal changes in living conditions in their respective housing careers. We use four different aspects of housing as indicators of living conditions from a survey conducted by the World Bank Group that captured the residential history of 2,397 individuals in Dar es Salaam from a spatially representative sample of households. We find that improvements in housing conditions are uneven, a considerable proportion of individuals remained perpetually deprived of adequate housing despite migrating from rural areas to Dar es Salaam and changing multiple homes within the city during their tenure. Our findings indicate that housing disparities persist over time for many. Socioeconomic groups such as migrants tend to experience significant improvements after moving to the city but show limited upward mobility afterwards, an aspect that is rarely addressed in policy discourse on equitable access to adequate housing.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239735PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523954PMC
December 2020

Using Lower Amplitudes to Maintain Effective High Dose Spinal Cord Stimulation Therapy (SCS Dosing Pilot Study).

Neuromodulation 2020 Sep 18. Epub 2020 Sep 18.

Medtronic, Minneapolis, MN, USA.

Background: Spinal cord stimulation is an effective therapy for chronic back and/or leg pain. Amplitude dose-response studies are lacking; therefore, little guidance exists regarding the minimum amplitude requirements with specific high dose parameters. This study characterized the minimum amplitude level that maintained SCS therapy satisfaction and pain relief when stimulating at 1000 Hz and 90 μsec.

Materials And Methods: Qualified patients had back and leg pain, an implanted neurostimulator programmed to 1000 Hz and 90 μsec, and were very or somewhat satisfied with the therapy, and an average overall VAS pain score ≤ 4 from a daily diary. Patients received four blinded amplitudes (titrated from 80%, 60%, 40%, and 20% of baseline perception threshold), approximately two weeks each, with 1000 Hz and 90 μsec and position-adaptive stimulation enabled. Patients' satisfaction and overall VAS pain scores were collected for each period. All patients continued through the study, even after reporting lack of therapy satisfaction or pain relief.

Results: The minimum amplitude, which maintained therapy satisfaction, was 80% of perception threshold for two patients, 60% for one patient, and 20% for 21 patients. Additionally, six patients lost satisfaction changing from their baseline amplitude to 80% perception threshold. The minimum amplitude level, which maintained overall pain relief, was 80% perception threshold for three patients, 60% perception threshold for one patient, 40% perception threshold for two patients, and 20% perception threshold for 19 patients. Five patients required the setting they were programmed to during the baseline period.

Conclusion: The qualified study patients defined an implanted population reporting good pain relief and satisfaction using HD SCS therapy at baseline. The majority of these patients were able to maintain therapy satisfaction and pain relief (70% and 63.3%, respectively) with 20% perception threshold amplitude. Amplitudes below perception threshold could potentially maintain effective SCS therapy with HD stimulation in a subset of patients.
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http://dx.doi.org/10.1111/ner.13258DOI Listing
September 2020

Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study.

Nat Med 2020 11 14;26(11):1720-1725. Epub 2020 Sep 14.

Department of Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

The therapeutic potential of donor-derived mesenchymal stromal cells (MSCs) has been investigated in diverse diseases, including steroid-resistant acute graft versus host disease (SR-aGvHD). However, conventional manufacturing approaches are hampered by challenges with scalability and interdonor variability, and clinical trials have shown inconsistent outcomes. Induced pluripotent stem cells (iPSCs) have the potential to overcome these challenges, due to their capacity for multilineage differentiation and indefinite proliferation. Nonetheless, human clinical trials of iPSC-derived cells have not previously been completed. CYP-001 (iPSC-derived MSCs) is produced using an optimized, good manufacturing practice (GMP)-compliant manufacturing process. We conducted a phase 1, open-label clinical trial (no. NCT02923375) in subjects with SR-aGvHD. Sixteen subjects were screened and sequentially assigned to cohort A or cohort B (n = 8 per group). One subject in cohort B withdrew before receiving CYP-001 and was excluded from analysis. All other subjects received intravenous infusions of CYP-001 on days 0 and 7, at a dose level of either 1 × 10 cells per kg body weight, to a maximum of 1 × 10 cells per infusion (cohort A), or 2 × 10 cells per kg body weight, to a maximum dose of 2 × 10 cells per infusion (cohort B). The primary objective was to assess the safety and tolerability of CYP-001, while the secondary objectives were to evaluate efficacy based on the proportion of participants who showed a complete response (CR), overall response (OR) and overall survival (OS) by days 28/100. CYP-001 was safe and well tolerated. No serious adverse events were assessed as related to CYP-001. OR, CR and OS rates by day 100 were 86.7, 53.3 and 86.7%, respectively. The therapeutic application of iPSC-derived MSCs may now be explored in diverse inflammatory and immune-mediated diseases.
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http://dx.doi.org/10.1038/s41591-020-1050-xDOI Listing
November 2020

Dialysis Disequilibrium Syndrome and Cerebellar Herniation with Successful Reversal Using Mannitol.

Case Rep Nephrol 2020 25;2020:8850850. Epub 2020 Aug 25.

Department of Medicine-Division of Nephrology, Truman Medical Center, Kansas City, MO 64108, USA.

Dialysis disequilibrium syndrome (DDS) is a morbid but rare complication of dialysis. Feared sequalae of this diagnosis are brain herniation and death. This report presents a patient who was diagnosed with DDS with subsequent tonsillar herniation shown on imaging with complete resolution of clinical signs and symptoms, as well as imaging findings of herniation after prompt initiation of intravenous mannitol. This is the first known case of reversal and survival of DDS-induced tonsillar herniation using mannitol.
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http://dx.doi.org/10.1155/2020/8850850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468602PMC
August 2020

Reduction in intestinal colonization and invasion of internal organs after challenge by homologous and heterologous serovars of following vaccination of chickens with a novel trivalent inactivated vaccine.

Avian Pathol 2020 Dec 29;49(6):666-677. Epub 2020 Oct 29.

MSD Animal Health, Boxmeer, Netherlands.

A novel inactivated vaccine, comprising three serovars of (Enteritidis, serogroup O:9; Typhimurium, serogroup O:4; Infantis, serogroup O:7) grown under conditions of iron restriction and adjuvanted with aluminium hydroxide, was evaluated for efficacy following challenge by homologous and heterologous serovars. Chickens were vaccinated at 6 and 10 weeks of age by the intramuscular route and challenged 4 to 9 weeks after the second vaccination with serovars belonging to serogroup O:9 (Enteritidis), O:4 (Typhimurium and Heidelberg), O:7 (Infantis and Virchow), and O:8 (Hadar). All vaccinated birds produced a marked systemic antibody response against each of the component vaccine antigens by the time of challenge. Significant reductions in both colonization of the intestinal tract and invasion of internal organs were observed in vaccinated birds compared with non-vaccinated controls, irrespective of the challenge serovar. The findings suggest that broad serovar protection within the constitutive serogroups of an inactivated multi-valent vaccine is possible and could, therefore, play an important role in future control programmes. Novel inactivated trivalent chicken vaccine was developed and tested. Vaccine induced marked systemic antibody response against all vaccine antigens. Significant reductions in intestinal tract colonization and internal organ invasion. Vaccine efficacy demonstrated against homologous and heterologous serovars.
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http://dx.doi.org/10.1080/03079457.2020.1814200DOI Listing
December 2020

Safety and efficacy of a novel inactivated trivalent Salmonella enterica vaccine in chickens.

Vaccine 2020 10 2;38(43):6741-6750. Epub 2020 Sep 2.

MSD Animal Health, Wim de Körverstraat 35, 5831 AN Boxmeer, Netherlands. Electronic address:

Food poisoning in humans caused by Salmonella enterica remains a significant global public health concern, with the majority of infections associated with the consumption of contaminated eggs or poultry products. The safety and efficacy of a novel inactivated trivalent Salmonella enterica vaccine containing in addition to Salmonella serovars Enteritidis (O:9, serogroup D) and Typhimurium (O:4, serogroup B) also serovar Infantis (O:7, serogroup C1) formulated with an aluminium hydroxide-gel adjuvant was evaluated under field conditions. A total of 10,229 broiler breeder pullets, housed under commercial conditions, were vaccinated at 10 and 17 weeks of age by the intramuscular route in the breast muscle. The vaccine was safe with no local or systemic reactions or adverse effects on bird performance related to the vaccine detected. Vaccination resulted in notable increases in serovar specific antibodies that were maintained until at least 56 weeks of age. Vaccinated birds subjected to homologous challenges around onset of lay showed significantly reduced faecal shedding and organ invasion. Following heterologous challenge with S. Hadar (O:8, serogroup C2) faecal shedding was significantly reduced. These results demonstrate that this novel vaccine could play a significant role in a comprehensive Salmonella control programme intended to reduce both the incidence of food poisoning in humans and the use of antibiotics during poultry production.
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http://dx.doi.org/10.1016/j.vaccine.2020.08.033DOI Listing
October 2020

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Authors:
Derek C Angus Lennie Derde Farah Al-Beidh Djillali Annane Yaseen Arabi Abigail Beane Wilma van Bentum-Puijk Lindsay Berry Zahra Bhimani Marc Bonten Charlotte Bradbury Frank Brunkhorst Meredith Buxton Adrian Buzgau Allen C Cheng Menno de Jong Michelle Detry Lise Estcourt Mark Fitzgerald Herman Goossens Cameron Green Rashan Haniffa Alisa M Higgins Christopher Horvat Sebastiaan J Hullegie Peter Kruger Francois Lamontagne Patrick R Lawler Kelsey Linstrum Edward Litton Elizabeth Lorenzi John Marshall Daniel McAuley Anna McGlothin Shay McGuinness Bryan McVerry Stephanie Montgomery Paul Mouncey Srinivas Murthy Alistair Nichol Rachael Parke Jane Parker Kathryn Rowan Ashish Sanil Marlene Santos Christina Saunders Christopher Seymour Anne Turner Frank van de Veerdonk Balasubramanian Venkatesh Ryan Zarychanski Scott Berry Roger J Lewis Colin McArthur Steven A Webb Anthony C Gordon Farah Al-Beidh Derek Angus Djillali Annane Yaseen Arabi Wilma van Bentum-Puijk Scott Berry Abigail Beane Zahra Bhimani Marc Bonten Charlotte Bradbury Frank Brunkhorst Meredith Buxton Allen Cheng Menno De Jong Lennie Derde Lise Estcourt Herman Goossens Anthony Gordon Cameron Green Rashan Haniffa Francois Lamontagne Patrick Lawler Edward Litton John Marshall Colin McArthur Daniel McAuley Shay McGuinness Bryan McVerry Stephanie Montgomery Paul Mouncey Srinivas Murthy Alistair Nichol Rachael Parke Kathryn Rowan Christopher Seymour Anne Turner Frank van de Veerdonk Steve Webb Ryan Zarychanski Lewis Campbell Andrew Forbes David Gattas Stephane Heritier Lisa Higgins Peter Kruger Sandra Peake Jeffrey Presneill Ian Seppelt Tony Trapani Paul Young Sean Bagshaw Nick Daneman Niall Ferguson Cheryl Misak Marlene Santos Sebastiaan Hullegie Mathias Pletz Gernot Rohde Kathy Rowan Brian Alexander Kim Basile Timothy Girard Christopher Horvat David Huang Kelsey Linstrum Jennifer Vates Richard Beasley Robert Fowler Steve McGloughlin Susan Morpeth David Paterson Bala Venkatesh Tim Uyeki Kenneth Baillie Eamon Duffy Rob Fowler Thomas Hills Katrina Orr Asad Patanwala Steve Tong Mihai Netea Shilesh Bihari Marc Carrier Dean Fergusson Ewan Goligher Ghady Haidar Beverley Hunt Anand Kumar Mike Laffan Patrick Lawless Sylvain Lother Peter McCallum Saskia Middeldopr Zoe McQuilten Matthew Neal John Pasi Roger Schutgens Simon Stanworth Alexis Turgeon Alexandra Weissman Neill Adhikari Matthew Anstey Emily Brant Angelique de Man Francois Lamonagne Marie-Helene Masse Andrew Udy Donald Arnold Phillipe Begin Richard Charlewood Michael Chasse Mark Coyne Jamie Cooper James Daly Iain Gosbell Heli Harvala-Simmonds Tom Hills Sheila MacLennan David Menon John McDyer Nicole Pridee David Roberts Manu Shankar-Hari Helen Thomas Alan Tinmouth Darrell Triulzi Tim Walsh Erica Wood Carolyn Calfee Cecilia O’Kane Murali Shyamsundar Pratik Sinha Taylor Thompson Ian Young Shailesh Bihari Carol Hodgson John Laffey Danny McAuley Neil Orford Ary Neto Michelle Detry Mark Fitzgerald Roger Lewis Anna McGlothlin Ashish Sanil Christina Saunders Lindsay Berry Elizabeth Lorenzi Eliza Miller Vanessa Singh Claire Zammit Wilma van Bentum Puijk Wietske Bouwman Yara Mangindaan Lorraine Parker Svenja Peters Ilse Rietveld Kik Raymakers Radhika Ganpat Nicole Brillinger Rene Markgraf Kate Ainscough Kathy Brickell Aisha Anjum Janis-Best Lane Alvin Richards-Belle Michelle Saull Daisy Wiley Julian Bion Jason Connor Simon Gates Victoria Manax Tom van der Poll John Reynolds Marloes van Beurden Evelien Effelaar Joost Schotsman Craig Boyd Cain Harland Audrey Shearer Jess Wren Giles Clermont William Garrard Kyle Kalchthaler Andrew King Daniel Ricketts Salim Malakoutis Oscar Marroquin Edvin Music Kevin Quinn Heidi Cate Karen Pearson Joanne Collins Jane Hanson Penny Williams Shane Jackson Adeeba Asghar Sarah Dyas Mihaela Sutu Sheenagh Murphy Dawn Williamson Nhlanhla Mguni Alison Potter David Porter Jayne Goodwin Clare Rook Susie Harrison Hannah Williams Hilary Campbell Kaatje Lomme James Williamson Jonathan Sheffield Willian van’t Hoff Phobe McCracken Meredith Young Jasmin Board Emma Mart Cameron Knott Julie Smith Catherine Boschert Julia Affleck Mahesh Ramanan Ramsy D’Souza Kelsey Pateman Arif Shakih Winston Cheung Mark Kol Helen Wong Asim Shah Atul Wagh Joanne Simpson Graeme Duke Peter Chan Brittney Cartner Stephanie Hunter Russell Laver Tapaswi Shrestha Adrian Regli Annamaria Pellicano James McCullough Mandy Tallott Nikhil Kumar Rakshit Panwar Gail Brinkerhoff Cassandra Koppen Federica Cazzola Matthew Brain Sarah Mineall Roy Fischer Vishwanath Biradar Natalie Soar Hayden White Kristen Estensen Lynette Morrison Joanne Smith Melanie Cooper Monash Health Yahya Shehabi Wisam Al-Bassam Amanda Hulley Christina Whitehead Julie Lowrey Rebecca Gresha James Walsham Jason Meyer Meg Harward Ellen Venz Patricia Williams Catherine Kurenda Kirsy Smith Margaret Smith Rebecca Garcia Deborah Barge Deborah Byrne Kathleen Byrne Alana Driscoll Louise Fortune Pierre Janin Elizabeth Yarad Naomi Hammond Frances Bass Angela Ashelford Sharon Waterson Steve Wedd Robert McNamara Heidi Buhr Jennifer Coles Sacha Schweikert Bradley Wibrow Rashmi Rauniyar Erina Myers Ed Fysh Ashlish Dawda Bhaumik Mevavala Ed Litton Janet Ferrier Priya Nair Hergen Buscher Claire Reynolds John Santamaria Leanne Barbazza Jennifer Homes Roger Smith Lauren Murray Jane Brailsford Loretta Forbes Teena Maguire Vasanth Mariappa Judith Smith Scott Simpson Matthew Maiden Allsion Bone Michelle Horton Tania Salerno Martin Sterba Wenli Geng Pieter Depuydt Jan De Waele Liesbet De Bus Jan Fierens Stephanie Bracke Brenda Reeve William Dechert Michaël Chassé François Martin Carrier Dounia Boumahni Fatna Benettaib Ali Ghamraoui David Bellemare Ève Cloutier Charles Francoeur François Lamontagne Frédérick D’Aragon Elaine Carbonneau Julie Leblond Gloria Vazquez-Grande Nicole Marten Maggie Wilson Martin Albert Karim Serri Alexandros Cavayas Mathilde Duplaix Virginie Williams Bram Rochwerg Tim Karachi Simon Oczkowski John Centofanti Tina Millen Erick Duan Jennifer Tsang Lisa Patterson Shane English Irene Watpool Rebecca Porteous Sydney Miezitis Lauralyn McIntyre Laurent Brochard Karen Burns Gyan Sandhu Imrana Khalid Alexandra Binnie Elizabeth Powell Alexandra McMillan Tracy Luk Noah Aref Zdravko Andric Sabina Cviljevic Renata Đimoti Marija Zapalac Gordan Mirković Bruno Baršić Marko Kutleša Viktor Kotarski Ana Vujaklija Brajković Jakša Babel Helena Sever Lidija Dragija Ira Kušan Suvi Vaara Leena Pettilä Jonna Heinonen Anne Kuitunen Sari Karlsson Annukka Vahtera Heikki Kiiski Sanna Ristimäki Amine Azaiz Cyril Charron Mathieu Godement Guillaume Geri Antoine Vieillard-Baron Franck Pourcine Mehran Monchi David Luis Romain Mercier Anne Sagnier Nathalie Verrier Cecile Caplin Shidasp Siami Christelle Aparicio Sarah Vautier Asma Jeblaoui Muriel Fartoukh Laura Courtin Vincent Labbe Cécile Leparco Grégoire Muller Mai-Anh Nay Toufik Kamel Dalila Benzekri Sophie Jacquier Emmanuelle Mercier Delphine Chartier Charlotte Salmon PierreFrançois Dequin Francis Schneider Guillaume Morel Sylvie L’Hotellier Julio Badie Fernando Daniel Berdaguer Sylvain Malfroy Chaouki Mezher Charlotte Bourgoin Bruno Megarbane Sebastian Voicu Nicolas Deye Isabelle Malissin Laetitia Sutterlin Christophe Guitton Cédric Darreau Mickaël Landais Nicolas Chudeau Alain Robert Pierre Moine Nicholas Heming Virginie Maxime Isabelle Bossard Tiphaine Barbarin Nicholier Gwenhael Colin Vanessa Zinzoni Natacham Maquigneau André Finn Gabriele Kreß Uwe Hoff Carl Friedrich Hinrichs Jens Nee Mathias Pletz Stefan Hagel Juliane Ankert Steffi Kolanos Frank Bloos Sirak Petros Bastian Pasieka Kevin Kunz Peter Appelt Bianka Schütze Stefan Kluge Axel Nierhaus Dominik Jarczak Kevin Roedl Dirk Weismann Anna Frey Vivantes Klinikum Neukölln Lorenz Reill Michael Distler Astrid Maselli János Bélteczki István Magyar Ágnes Fazekas Sándor Kovács Viktória Szőke Gábor Szigligeti János Leszkoven Daniel Collins Patrick Breen Stephen Frohlich Ruth Whelan Bairbre McNicholas Michael Scully Siobhan Casey Maeve Kernan Peter Doran Michael O’Dywer Michelle Smyth Leanne Hayes Oscar Hoiting Marco Peters Els Rengers Mirjam Evers Anton Prinssen Jeroen Bosch Ziekenhuis Koen Simons Wim Rozendaal F Polderman P de Jager M Moviat A Paling A Salet Emma Rademaker Anna Linda Peters E de Jonge J Wigbers E Guilder M Butler Keri-Anne Cowdrey Lynette Newby Yan Chen Catherine Simmonds Rachael McConnochie Jay Ritzema Carter Seton Henderson Kym Van Der Heyden Jan Mehrtens Tony Williams Alex Kazemi Rima Song Vivian Lai Dinu Girijadevi Robert Everitt Robert Russell Danielle Hacking Ulrike Buehner Erin Williams Troy Browne Kate Grimwade Jennifer Goodson Owen Keet Owen Callender Robert Martynoga Kara Trask Amelia Butler Livia Schischka Chelsea Young Eden Lesona Shaanti Olatunji Yvonne Robertson Nuno José Teodoro Amaro dos Santos Catorze Tiago Nuno Alfaro de Lima Pereira Lucilia Maria Neves Pessoa Ricardo Manuel Castro Ferreira Joana Margarida Pereira Sousa Bastos Simin Aysel Florescu Delia Stanciu Miahela Florentina Zaharia Alma Gabriela Kosa Daniel Codreanu Yaseen Marabi Eman Al Qasim Mohamned Moneer Hagazy Lolowa Al Swaidan Hatim Arishi Rosana Muñoz-Bermúdez Judith Marin-Corral Anna Salazar Degracia Francisco Parrilla Gómez Maria Isabel Mateo López Jorge Rodriguez Fernandez Sheila Cárcel Fernández Rosario Carmona Flores Rafael León López Carmen de la Fuente Martos Angela Allan Petra Polgarova Neda Farahi Stephen McWilliam Daniel Hawcutt Laura Rad Laura O’Malley Jennifer Whitbread Olivia Kelsall Laura Wild Jessica Thrush Hannah Wood Karen Austin Adrian Donnelly Martin Kelly Sinéad O’Kane Declan McClintock Majella Warnock Paul Johnston Linda Jude Gallagher Clare Mc Goldrick Moyra Mc Master Anna Strzelecka Rajeev Jha Michael Kalogirou Christine Ellis Vinodh Krishnamurthy Vashish Deelchand Jon Silversides Peter McGuigan Kathryn Ward Aisling O’Neill Stephanie Finn Barbara Phillips Dee Mullan Laura Oritz-Ruiz de Gordoa Matthew Thomas Katie Sweet Lisa Grimmer Rebekah Johnson Jez Pinnell Matt Robinson Lisa Gledhill Tracy Wood Matt Morgan Jade Cole Helen Hill Michelle Davies David Antcliffe Maie Templeton Roceld Rojo Phoebe Coghlan Joanna Smee Euan Mackay Jon Cort Amanda Whileman Thomas Spencer Nick Spittle Vidya Kasipandian Amit Patel Suzanne Allibone Roman Mary Genetu Mohamed Ramali Alison Ghosh Peter Bamford Emily London Kathryn Cawley Maria Faulkner Helen Jeffrey Tim Smith Chris Brewer Jane Gregory James Limb Amanda Cowton Julie O’Brien Nikitas Nikitas Colin Wells Liana Lankester Mark Pulletz Patricia Williams Jenny Birch Sophie Wiseman Sarah Horton Ana Alegria Salah Turki Tarek Elsefi Nikki Crisp Louise Allen Iain McCullagh Philip Robinson Carole Hays Maite Babio-Galan Hannah Stevenson Divya Khare Meredith Pinder Selvin Selvamoni Amitha Gopinath Richard Pugh Daniel Menzies Callum Mackay Elizabeth Allan Gwyneth Davies Kathryn Puxty Claire McCue Susanne Cathcart Naomi Hickey Jane Ireland Hakeem Yusuff Graziella Isgro Chris Brightling Michelle Bourne Michelle Craner Malcolm Watters Rachel Prout Louisa Davies Suzannah Pegler Lynsey Kyeremeh Gill Arbane Karen Wilson Linda Gomm Federica Francia Stephen Brett Sonia Sousa Arias Rebecca Elin Hall Joanna Budd Charlotte Small Janine Birch Emma Collins Jeremy Henning Stephen Bonner Keith Hugill Emanuel Cirstea Dean Wilkinson Michal Karlikowski Helen Sutherland Elva Wilhelmsen Jane Woods Julie North Dhinesh Sundaran Laszlo Hollos Susan Coburn Joanne Walsh Margaret Turns Phil Hopkins John Smith Harriet Noble Maria Theresa Depante Emma Clarey Shondipon Laha Mark Verlander Alexandra Williams Abby Huckle Andrew Hall Jill Cooke Caroline Gardiner-Hill Carolyn Maloney Hafiz Qureshi Neil Flint Sarah Nicholson Sara Southin Andrew Nicholson Barbara Borgatta Ian Turner-Bone Amie Reddy Laura Wilding Loku Chamara Warnapura Ronan Agno Sathianathan David Golden Ciaran Hart Jo Jones Jonathan Bannard-Smith Joanne Henry Katie Birchall Fiona Pomeroy Rachael Quayle Arystarch Makowski Beata Misztal Iram Ahmed Thyra KyereDiabour Kevin Naiker Richard Stewart Esther Mwaura Louise Mew Lynn Wren Felicity Willams Richard Innes Patricia Doble Joanne Hutter Charmaine Shovelton Benjamin Plumb Tamas Szakmany Vincent Hamlyn Nancy Hawkins Sarah Lewis Amanda Dell Shameer Gopal Saibal Ganguly Andrew Smallwood Nichola Harris Stella Metherell Juan Martin Lazaro Tabitha Newman Simon Fletcher Jurgens Nortje Deirdre Fottrell-Gould Georgina Randell Mohsin Zaman Einas Elmahi Andrea Jones Kathryn Hall Gary Mills Kim Ryalls Helen Bowler Jas Sall Richard Bourne Zoe Borrill Tracey Duncan Thomas Lamb Joanne Shaw Claire Fox Jeronimo Moreno Cuesta Kugan Xavier Dharam Purohit Munzir Elhassan Dhanalakshmi Bakthavatsalam Matthew Rowland Paula Hutton Archana Bashyal Neil Davidson Clare Hird Manish Chhablani Gunjan Phalod Amy Kirkby Simon Archer Kimberley Netherton Henrik Reschreiter Julie Camsooksai Sarah Patch Sarah Jenkins David Pogson Steve Rose Zoe Daly Lutece Brimfield Helen Claridge Dhruv Parekh Colin Bergin Michelle Bates Joanne Dasgin Christopher McGhee Malcolm Sim Sophie Kennedy Hay Steven Henderson Mandeep-Kaur Phull Abbas Zaidi Tatiana Pogreban Lace Paulyn Rosaroso Daniel Harvey Benjamin Lowe Megan Meredith Lucy Ryan Anil Hormis Rachel Walker Dawn Collier Sarah Kimpton Susan Oakley Kevin Rooney Natalie Rodden Emma Hughes Nicola Thomson Deborah McGlynn Andrew Walden Nicola Jacques Holly Coles Emma Tilney Emma Vowell Martin Schuster-Bruce Sally Pitts Rebecca Miln Laura Purandare Luke Vamplew Michael Spivey Sarah Bean Karen Burt Lorraine Moore Christopher Day Charly Gibson Elizabeth Gordon Letizia Zitter Samantha Keenan Evelyn Baker Shiney Cherian Sean Cutler Anna Roynon-Reed Kate Harrington Ajay Raithatha Kris Bauchmuller Norfaizan Ahmad Irina Grecu Dawn Trodd Jane Martin Caroline Wrey Brown Ana-Marie Arias Thomas Craven David Hope Jo Singleton Sarah Clark Nicola Rae Ingeborg Welters David Oliver Hamilton Karen Williams Victoria Waugh David Shaw Zudin Puthucheary Timothy Martin Filipa Santos Ruzena Uddin Alastair Somerville Kate Colette Tatham Shaman Jhanji Ethel Black Arnold Dela Rosa Ryan Howle Redmond Tully Andrew Drummond Joy Dearden Jennifer Philbin Sheila Munt Alain Vuylsteke Charles Chan Saji Victor Ramprasad Matsa Minerva Gellamucho Ben Creagh-Brown Joe Tooley Laura Montague Fiona De Beaux Laetitia Bullman Ian Kersiake Carrie Demetriou Sarah Mitchard Lidia Ramos Katie White Phil Donnison Maggie Johns Ruth Casey Lehentha Mattocks Sarah Salisbury Paul Dark Andrew Claxton Danielle McLachlan Kathryn Slevin Stephanie Lee Jonathan Hulme Sibet Joseph Fiona Kinney Ho Jan Senya Aneta Oborska Abdul Kayani Bernard Hadebe Rajalakshmi Orath Prabakaran Lesley Nichols Matt Thomas Ruth Worner Beverley Faulkner Emma Gendall Kati Hayes Colin Hamilton-Davies Carmen Chan Celina Mfuko Hakam Abbass Vineela Mandadapu Susannah Leaver Daniel Forton Kamal Patel Elankumaran Paramasivam Matthew Powell Richard Gould Elizabeth Wilby Clare Howcroft Dorota Banach Ziortza Fernández de Pinedo Artaraz Leilani Cabreros Ian White Maria Croft Nicky Holland Rita Pereira Ahmed Zaki David Johnson Matthew Jackson Hywel Garrard Vera Juhaz Alistair Roy Anthony Rostron Lindsey Woods Sarah Cornell Suresh Pillai Rachel Harford Tabitha Rees Helen Ivatt Ajay Sundara Raman Miriam Davey Kelvin Lee Russell Barber Manish Chablani Farooq Brohi Vijay Jagannathan Michele Clark Sarah Purvis Bill Wetherill Ahilanandan Dushianthan Rebecca Cusack Kim de Courcy-Golder Simon Smith Susan Jackson Ben Attwood Penny Parsons Valerie Page Xiao Bei Zhao Deepali Oza Jonathan Rhodes Tom Anderson Sheila Morris Charlotte Xia Le Tai Amy Thomas Alexandra Keen Stephen Digby Nicholas Cowley Laura Wild David Southern Harsha Reddy Andy Campbell Claire Watkins Sara Smuts Omar Touma Nicky Barnes Peter Alexander Tim Felton Susan Ferguson Katharine Sellers Joanne Bradley-Potts David Yates Isobel Birkinshaw Kay Kell Nicola Marshall Lisa Carr-Knott Charlotte Summers

JAMA 2020 10;324(13):1317-1329

Division of Anaesthetics, Pain Medicine and Intensive Care Medicine, Department of Surgery and Cancer, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.

Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).

Main Outcomes And Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).

Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.

Conclusions And Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.
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http://dx.doi.org/10.1001/jama.2020.17022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489418PMC
October 2020

Spotlight: Gastrointestinal Evaluation of Iron Deficiency Anemia.

Gastroenterology 2020 Sep 25;159(3):1096. Epub 2020 Aug 25.

Department of Medicine, Medical University of South Carolina, Charleston, SC.

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http://dx.doi.org/10.1053/j.gastro.2020.08.036DOI Listing
September 2020

Spectral-Spatial Features Integrated Convolution Neural Network for Breast Cancer Classification.

Sensors (Basel) 2020 Aug 22;20(17). Epub 2020 Aug 22.

CHARUSAT Space Research and Technology Center, Charotar University of Science and Technology, Changa, Gujarat 388421, India.

Cancer identification and classification from histopathological images of the breast depends greatly on experts, and computer-aided diagnosis can play an important role in disagreement of experts. This automatic process has increased the accuracy of the classification at a reduced cost. The advancement in Convolution Neural Network (CNN) structure has outperformed the traditional approaches in biomedical imaging applications. One of the limiting factors of CNN is it uses spatial image features only for classification. The spectral features from the transform domain have equivalent importance in the complex image classification algorithm. This paper proposes a new CNN structure to classify the histopathological cancer images based on integrating the spectral features obtained using a multi-resolution wavelet transform with the spatial features of CNN. In addition, batch normalization process is used after every layer in the convolution network to improve the poor convergence problem of CNN and the deep layers of CNN are trained with spectral-spatial features. The proposed structure is tested on malignant histology images of the breast for both binary and multi-class classification of tissue using the BreaKHis Dataset and the Breast Cancer Classification Challenge 2015 Datasest. Experimental results show that the combination of spectral-spatial features improves classification accuracy of the CNN network and requires less training parameters in comparison with the well known models (i.e., VGG16 and ALEXNET). The proposed structure achieves an average accuracy of 97.58% and 97.45% with 7.6 million training parameters on both datasets, respectively.
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http://dx.doi.org/10.3390/s20174747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506633PMC
August 2020

Preventing COVID-19 Amid Public Health and Urban Planning Failures in Slums of Indian Cities.

Authors:
Amit Patel

World Med Health Policy 2020 Jul 14. Epub 2020 Jul 14.

The COVID-19 pandemic has brought renewed attention to the lack of urban planning and its public health implications in developing countries. Slum communities face the dual challenges of chronically poor residential environments and the acute effects of a pandemic and the preventive measures that follow. In this paper, I assess the effectiveness and implications of social distancing, frequent handwashing, and lockdown in the context of slums in Indian cities, where overcrowding, lack of access to water and sanitation, and dependence on daily wages for sustenance and livelihood are common. Using data from multiple sources, I demonstrate that not only will these measures be hard to achieve in slums in the short term due to specific characteristics of these habitats, but they will bring new challenges in the long term due to disproportionate impacts on the urban poor. Lessons learned from this pandemic will require us to rethink public health responses and urban planning practices that could better prepare our cities for future pandemics.
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http://dx.doi.org/10.1002/wmh3.351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404953PMC
July 2020