Relevance of prediction scores derived from the SARS-CoV-2 first wave, in the evolving UK COVID-19 second wave, for safe early discharge and mortality: a PREDICT COVID-19 UK prospective observational cohort study.

OBJECTIVE: Prospectively validate prognostication scores, SOARS and 4C Mortality Score, derived from the COVID-19 first wave, for mortality and safe early discharge in the evolving pandemic with SARS-CoV-2 variants (B.1.1.7 replacing D614) and healthcare responses altering patient demographic and mortality. DESIGN: Protocol-based prospective observational cohort study. SETTING: Single site PREDICT and multisite ISARIC (International Severe Acute Respiratory and Emerging Infections Consortium) cohorts in UK COVID-19 second wave, October 2020 to January 2021. PARTICIPANTS: 1383 PREDICT and 20 595 ISARIC SARS-CoV-2 patients. PRIMARY OUTCOME MEASURES: Relevance of SOARS and 4C Mortality Score determining in-hospital mortality and safe early discharge in the evolving UK COVID-19 second wave. RESULTS: 1383 (median age 67 years, IQR 52-82; mortality 24.7%) PREDICT and 20 595 (mortality 19.4%) ISARIC patient cohorts showed SOARS had area under the curve (AUC) of 0.8 and 0.74, while 4C Mortality Score had AUC of 0.83 and 0.91 for hospital mortality, in the PREDICT and ISARIC cohorts respectively, therefore, effective in evaluating safe discharge and in-hospital mortality. 19.3% (231/1195, PREDICT cohort) and 16.7% (2550/14992, ISARIC cohort) with SOARS of 0-1 were candidates for safe discharge to a virtual hospital (VH) model. SOARS implementation in the VH pathway resulted in low readmission, 11.8% (27/229) and low mortality, 0.9% (2/229). Use to prevent admission is still suboptimal, as 8.1% in the PREDICT cohort and 9.5% in the ISARIC cohort were admitted despite SOARS score of 0-1. CONCLUSIONS: SOARS and 4C Mortality Score remains valid, transforming complex clinical presentations into tangible numbers, aiding objective decision making, despite SARS-CoV-2 variants and healthcare responses altering patient demographic and mortality. Both scores, easily implemented within urgent care pathways for safe early discharge, allocate hospital resources appropriately to the pandemic's needs while enabling normal healthcare services resumption.

Retrospective case-control study to evaluate hypocalcaemia as a distinguishing feature of COVID-19 compared with other infective pneumonias and its association with disease severity.

OBJECTIVES: To investigate whether calcium derangement was a specific feature of COVID-19 that distinguishes it from other infective pneumonias, and its association with disease severity. DESIGN: A retrospective observational case-control study looking at serum calcium on adult patients with COVID-19, and community-acquired pneumonia (CAP) or viral pneumonia (VP). SETTING: A district general hospital on the outskirts of London, UK. PARTICIPANTS: 506 patients with COVID-19, 95 patients with CAP and 152 patients with VP. OUTCOME MEASURES: Baseline characteristics including hypocalcaemia in patients with COVID-19, CAP and VP were detailed. For patients with COVID-19, the impact of an abnormally low calcium level on the maximum level of hospital care, as a surrogate of COVID-19 severity, was evaluated. The primary outcome of maximal level of care was based on the WHO Clinical Progression Scale for COVID-19. RESULTS: Hypocalcaemia was a specific and common clinical finding in patients with COVID-19 that distinguished it from other respiratory infections. Calcium levels were significantly lower in those with severe disease. Ordinal regression of risk estimates for categorised care levels showed that baseline hypocalcaemia was incrementally associated with OR of 2.33 (95% CI 1.5 to 3.61) for higher level of care, superior to other variables that have previously been shown to predict worse COVID-19 outcome. Serial calcium levels showed improvement by days 7-9 of admission, only in survivors of COVID-19. CONCLUSION: Hypocalcaemia is specific to COVID-19 and may help distinguish it from other infective pneumonias. Hypocalcaemia may independently predict severe disease and warrants detailed prognostic investigation. The fact that decreased serum calcium is observed at the time of clinical presentation in COVID-19, but not other infective pneumonias, suggests that its early derangement is pathophysiological and may influence the deleterious evolution of this disease. TRIAL REGISTRATION NUMBER: 20/HRA/2344.

Predictors of clinical deterioration in patients with suspected COVID-19 managed in a 'virtual hospital' setting: a cohort study.

OBJECTIVE: Identify predictors of clinical deterioration in a virtual hospital (VH) setting for COVID-19. DESIGN: Real-world prospective observational study. SETTING: VH remote assessment service in West Hertfordshire NHS Trust, UK. PARTICIPANTS: Patients with suspected COVID-19 illness enrolled directly from the community (postaccident and emergency (A&E) or medical intake assessment) or postinpatient admission. MAIN OUTCOME MEASURE: Death or (re-)admission to inpatient hospital care during VH follow-up and for 2 weeks post-VH discharge. RESULTS: 900 patients with a clinical diagnosis of COVID-19 (455 referred from A&E or medical intake and 445 postinpatient) were included in the analysis. 76 (8.4%) of these experienced clinical deterioration (15 deaths in admitted patients, 3 deaths in patients not admitted and 58 additional inpatient admissions). Predictors of clinical deterioration were increase in age (OR 1.04 (95% CI 1.02 to 1.06) per year of age), history of cancer (OR 2.87 (95% CI 1.41 to 5.82)), history of mental health problems (OR 1.76 (95% CI 1.02 to 3.04)), severely impaired renal function (OR for eGFR <30=9.09 (95% CI 2.01 to 41.09)) and having a positive SARS-CoV-2 PCR result (OR 2.0 (95% CI 1.11 to 3.60)). CONCLUSIONS: These predictors may help direct intensity of monitoring for patients with suspected or confirmed COVID-19 who are being remotely monitored by primary or secondary care services. Further research is needed to confirm our findings and identify the reasons for increased risk of clinical deterioration associated with cancer and mental health problems.

Early prognostication of COVID-19 to guide hospitalisation versus outpatient monitoring using a point-of-test risk prediction score.

INTRODUCTION: Risk factors of adverse outcomes in COVID-19 are defined but stratification of mortality using non-laboratory measured scores, particularly at the time of prehospital SARS-CoV-2 testing, is lacking. METHODS: Multivariate regression with bootstrapping was used to identify independent mortality predictors in patients admitted to an acute hospital with a confirmed diagnosis of COVID-19. Predictions were externally validated in a large random sample of the ISARIC cohort (N=14 231) and a smaller cohort from Aintree (N=290). RESULTS: 983 patients (median age 70, IQR 53-83; in-hospital mortality 29.9%) were recruited over an 11-week study period. Through sequential modelling, a five-predictor score termed SOARS (SpO2, Obesity, Age, Respiratory rate, Stroke history) was developed to correlate COVID-19 severity across low, moderate and high strata of mortality risk. The score discriminated well for in-hospital death, with area under the receiver operating characteristic values of 0.82, 0.80 and 0.74 in the derivation, Aintree and ISARIC validation cohorts, respectively. Its predictive accuracy (calibration) in both external cohorts was consistently higher in patients with milder disease (SOARS 0-1), the same individuals who could be identified for safe outpatient monitoring. Prediction of a non-fatal outcome in this group was accompanied by high score sensitivity (99.2%) and negative predictive value (95.9%). CONCLUSION: The SOARS score uses constitutive and readily assessed individual characteristics to predict the risk of COVID-19 death. Deployment of the score could potentially inform clinical triage in preadmission settings where expedient and reliable decision-making is key. The resurgence of SARS-CoV-2 transmission provides an opportunity to further validate and update its performance.

Rapid onsite evaluation uses a very small proportion of total material aspirated at endobronchial or endoscopic ultrasound in the investigation of suspected thoracic malignancy.

INTRODUCTION: The objectives were: to measure the proportion of aspirated material used to make direct slides for rapid onsite evaluation (ROSE) at endobronchial (EBUS) and endoscopic ultrasound (EUS) in suspected thoracic malignancy; and to correlate pass weights with ROSE category and needle size. METHOD: All EBUS and EUS cases for possible thoracic malignancy October 2018-May 2019 were included. All material from each pass was expelled into a Petri dish. One drop of material was placed on each of two slides; one used for ROSE, the other fixed and remaining material processed to cell block. Dish and slides were weighed before and after this procedure on a sensitive balance and weight of aspirate and slide material calculated. When ROSE identified malignancy, slide production ceased but target sampling for ancillary studies continued. RESULTS: ROSE accuracy was 96.8%. Mean percentage by target of aspirated material used to make direct slides for ROSE was 1.9% in malignant cases and 3.6% in non-malignant cases (P = .027 for difference). Mean percentage by pass was 5.9%. Mean weight of a single aspirate was 128.8 mg. Mean weight of aspirates insufficient on ROSE (175.7 mg) was significantly higher than the mean weight of benign or malignant aspirates (117.1 and 114.0 mg, respectively). Mean weight of aspirates using 22G needles (132.6 mg) was significantly higher than that for 25G needles (87.1 mg). CONCLUSION: Material made into direct slides at EBUS and EUS and used in part for ROSE uses a tiny proportion of aspirated material with over 98% processed to cell block and available for ancillary testing in malignant cases.

Pulmonary MALToma Synchronous with Metastatic Prostate Adenocarcinoma: A Diagnostic Challenge.

OBJECTIVE: We describe the novel case of a patient presenting with pulmonary mucosa-associated lymphoid tissue lymphoma (pMALToma) synchronous with metastatic prostate adenocarcinoma. MATERIALS AND METHODS: We report the clinical, laboratory, radiological and histological findings of the above patient. RESULTS: While the patient's metastatic prostate adenocarcinoma responded well to chemo-radio-hormonal therapy, a persistent area of lung consolidation was noted and further investigated, leading to the diagnosis of concurrent pMALToma. CONCLUSION: It is important to pursue further investigation when there appears to be persistent change or altered disease response in malignancy if there is evidence for disease response elsewhere, as there may be two synchronous primary cancers. LEARNING POINTS: This is a novel case where pulmonary mucosa-associated lymphoid tissue lymphoma (pMALToma), a rare disease entity, presented synchronously and asymptomatically in a patient with metastatic prostate adenocarcinoma.From an instructive errors perspective, it is important to consider synchronous primary malignancy and pursue further investigations, as appropriate, when there appears to be persistent change or altered disease response if there is evidence for disease response elsewhere.

Successful endobronchial ultrasound-guided transbronchial needle aspiration of tumour thrombus in the left pulmonary vein to achieve histological diagnosis.

A symptomatic 66-year-old gentleman presented with a large left upper lobe mass, thought likely to be malignant. Further imaging suggested direct tumour extension into the left pulmonary vein. During a subsequent EBUS (endobronchial ultrasound) histological diagnosis was not achieved from sampling higher order lymph nodes, thus intra-procedurally the decision to sample, by Transbronchial Needle Aspiration (TBNA), an area thought to relate to tumour thrombus in the left pulmonary vein was taken. A diagnosis of a non-small cell lung cancer was made on histological testing of the tumour thrombus sample. Considering the bleeding risk, direct probe contact with the endobronchial wall was maintained for several minutes but no bleeding was observed. There were no complications as a result of the procedure. It may be safe to sample tumour thrombus from within a pulmonary vein via EBUS-TBNA to achieve positive histology.

Testing for Common Respiratory Viruses in Children Admitted to Pediatric Intensive Care: Epidemiology and Outcomes.

OBJECTIVES: Viral infections are common in children, but there is a lack of data on severe viral infections in critically ill children. We investigated testing for viral infections in children requiring PICU admission and describe the epidemiology and outcomes. DESIGN: Multicenter retrospective study. Results of viral testing for nine respiratory viruses using polymerase chain reaction were collected. PARTICIPANTS: Children less than 16 years old nonelectively admitted to PICU over a 6-year period. SETTING: Two tertiary PICUs in Queensland, Australia. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Primary outcome was PICU length of stay. Secondary outcomes included need for and duration of intubation and mortality in PICU. Univariate and multivariate regression analyses were performed, adjusting for age, indigenous status, comorbidities, and severity of illness. RESULTS: Of 6,426 nonelective admissions, 2,956 (46%) were polymerase chain reaction tested for a virus of which 1,353 (46%) were virus positive. Respiratory syncytial virus was the most common pathogen identified (n = 518, 33%), followed by rhinovirus/enterovirus and adenovirus. Across all patients who underwent polymerase chain reaction testing, identification of a respiratory virus was not significantly associated with longer overall length of stay (multivariate odds ratio, 1.08; 95% CI, 0.99-1.17; p = 0.068) or longer intubation (p = 0.181), whereas the adjusted odds for intubation and mortality were significantly lower (p < 0.01). Subgroup analyses restricted to patients with acute respiratory infections (n = 1,241), bronchiolitis (n = 761), pneumonia (n = 311), confirmed bacterial infection (n = 345), and malignancy (n = 95) showed that patients positive for a virus on testing had significantly longer PICU length of stay (multivariate p < 0.05). In children with pneumonia, identification of a respiratory virus was associated with significantly increased duration of ventilation (p = 0.003). No association between positive test results for multiple viruses and outcomes was observed. CONCLUSION: Viral infections are common in critically ill children. Viral infections were associated with lower intubation and mortality rates compared with all children testing negative for viral infections. In several subgroups studied, identification of viral pathogens was associated with longer PICU length of stay while mortality was comparable. Prospective studies are required to determine the benefit of routine testing for respiratory viruses at the time of PICU admission.

Viral Respiratory Infections Diagnosed After PICU Admission.

OBJECTIVES: Reduction of nosocomial infections represents an increasingly recognized aspect of PICU benchmarking. We investigated the prevalence and outcomes of viral respiratory infections acquired during admission to PICU. DESIGN: Multicenter, statewide retrospective linkage study. SETTING: Tertiary PICU. PATIENTS: All children less than 16 years requiring PICU admission for greater than 48 hours from January 1, 2008, until December 31, 2013. INTERVENTION: Testing was performed in symptomatic patients using an extended panel polymerase chain reaction capturing nine respiratory viruses. Duration of intubation and total duration of respiratory support were primary outcomes. MEASUREMENTS AND MAIN RESULTS: Of 3,607 patients admitted to PICU for greater than 48 hours, 102 (2.8%) were diagnosed with a PICU-associated viral infection out of 702 patients (19.4%) undergoing viral testing, reflecting a rate of 2.8 PICU-associated viral infections per 1,000 PICU patient days. Compared with negative/untested patients, those with PICU-associated viral infections had greater intubation duration (median 164 vs 67; p< 0.001), longer respiratory support (204 vs 68 hr; p < 0.001), were more likely to require extracorporeal life support (odds ratio, 5.3; 2.7-10.3; p < 0.001), high-frequency oscillatory ventilation (odds ratio, 3.0; 1.7-5.4; p < 0.001), and inhaled nitric oxide (odds ratio, 2.7; 1.5-5.0; p = 0.001). When comparing patients with PICU-associated viral infection with patients who tested negative for respiratory viruses, no substantial difference in these outcomes was found. CONCLUSIONS: The acquisition of viral infections during PICU admission is less frequent compared with previous reports on bacterial and fungal hospital-acquired infections. We did not observe worse patient-centered outcomes when comparing virus positive versus tested but negative patients. Our findings challenge the clinical value of performing viral respiratory diagnostics in PICU patients evaluated for infection.

Severe Mycoplasma Pneumoniae Infection in Children Admitted to Pediatric Intensive Care.

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia and may cause life-threatening disease in children. We identified 30 (0.3%) confirmed M. pneumoniae cases by clinical and laboratory criteria in 11,526 pediatric intensive care unit admissions. Outcomes were comparable to patients admitted with other infections (n=3005; P > 0.1). Our findings indicate that empiric antimicrobial coverage for M. pneumoniae infection in pediatric intensive care unit is rarely needed.

Impact of Viral Respiratory Pathogens on Outcomes After Pediatric Cardiac Surgery.

OBJECTIVES: Viral respiratory infection is commonly considered a relative contraindication to elective cardiac surgery. We aimed to determine the frequency and outcomes of symptomatic viral respiratory infection in pediatric cardiac surgical patients. DESIGN: Retrospective cohort study of children undergoing cardiac surgery. Symptomatic children were tested using a multiplex Polymerase Chain Reaction (respiratory virus polymerase chain reaction) panel capturing nine respiratory viruses. Tests performed between 72 prior to and 48 hours after PICU admission were included. Mortality, length of stay in PICU, and intubation duration were investigated as outcomes. SETTING: Tertiary PICU providing state-wide pediatric cardiac services. PATIENTS: Children less than 18 years admitted January 1, 2008 to November 29, 2014 for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Respiratory virus polymerase chain reaction was positive in 73 (4.2%) of 1,737 pediatric cardiac surgical admissions, including 13 children with multiple viruses detected. Commonly detected viruses included rhino/enterovirus (48%), adenovirus (32%), parainfluenza virus 3 (10%), and respiratory syncytial virus (3%). Pediatric Index of Mortality 2, Aristotle scores, and cardiopulmonary bypass times were similar between virus positive and negative/untested cohorts. Respiratory virus polymerase chain reaction positive patients had a median 2.0 days greater PICU length of stay (p < 0.001) and longer intubation duration (p < 0.001). Multivariate analysis adjusting for age, Aristotle score, cardiopulmonary bypass duration, and need for preoperative PICU admission confirmed that virus positive patients had significantly greater intubation duration and PICU length of stay (p < 0.001). Virus positive patients were more likely to require PICU admission greater than 4 days (odds ratio, 3.5; 95% CI, 1.9-6.2) and more likely to require intubation greater than 48 hours (odds ratio, 2.5; 95% CI, 1.4-4.7). There was no difference in mortality. No association was found between coinfection and outcomes. CONCLUSIONS: Pediatric cardiac surgical patients with a respiratory virus detected at PICU admission had prolonged postoperative recovery with increased length of stay and duration of intubation. Our results suggest that postponing cardiac surgery in children with symptomatic viral respiratory infection is appropriate, unless the benefits of early surgery outweigh the risk of prolonged ventilation and PICU stay.

Life-threatening Vesicular Bronchial Injury Requiring Veno-venous Extracorporeal Membrane Oxygenation Rescue in an Electronic Nicotine Delivery System User.

The use of electronic nicotine delivery systems (ENDS) is increasing across the United States as tobacco bans increase and more people use these devices in an attempt to quit smoking. They are unregulated by the Food and Drug Administration, and there is significant concern that ENDS could produce several toxic byproducts. In this case a 35-year-old female presented to the emergency department with sudden-onset dyspnea. She denied current tobacco smoking, but she was a user of ENDS. When bronchoscopy was performed, an extensive pattern of suspected chemical injury was noted in her airways. She required transfer to a tertiary center where she required extracorporeal membranous oxygenation. Despite public opinion that ENDS are generally safe, or at least safer than tobacco smoking, contrary evidence is mounting. We postulate that her injuries were likely suffered secondary to use of an ENDS.

The vermiform appendix: a review.

New research on the vermiform appendix has shed light on its function. In further understanding the function of the appendix, this information should not negatively impact the clinical judgment in the event of appendicitis. Although the appendix and its pathology have been noted for centuries, it still presents a challenge in the operating room. The most common emergency surgical procedure performed is an appendectomy. Its highly variable position within the abdomen can cause confusion for clinicians. However, improved imaging modalities have heightened the physician's ability to diagnose disease of this organ. This article reviews germane literature regarding the human vermiform appendix.

Severe physical exertion, oxidative stress, and acute lung injury.

We report the case of a 27-year-old male athlete presenting with severe dyspnoea 24 hours after completing an "Ironman Triathlon." Subsequent chest radiology excluded pulmonary embolus but confirmed an acute lung injury (ALI). Echocardiography corroborated a normal brain natriuretic peptide level by demonstrating good biventricular systolic function with no regional wall motion abnormalities. He recovered well, without requiring ventilatory support, on supplemental oxygen therapy and empirical antibiotics. To date, ALI following severe physical exertion has never been described. Exercise is a form of physiological stress resulting in oxidative stress through generation of reactive oxygen/nitrogen species. In its extreme form, there is potential for an excessive oxidative stress response--one that overwhelms the body's protective antioxidant mechanisms. As our case demonstrated, oxidative stress secondary to severe physical exertion was the most likely factor in the pathogenesis of ALI. Further studies are necessary to explore the pathological consequences of exercise-induced oxidative stress. Although unproven as of yet, further research may be needed to demonstrate if antioxidant therapy can prevent or ameliorate potential life-threatening complications in the acute setting.

Colocalization analysis in fluorescence micrographs: verification of a more accurate calculation of pearson's correlation coefficient.

One of the most routine uses of fluorescence microscopy is colocalization, i.e., the demonstration of a relationship between pairs of biological molecules. Frequently this is presented simplistically by the use of overlays of red and green images, with areas of yellow indicating colocalization of the molecules. Colocalization data are rarely quantified and can be misleading. Our results from both synthetic and biological datasets demonstrate that the generation of Pearson's correlation coefficient between pairs of images can overestimate positive correlation and fail to demonstrate negative correlation. We have demonstrated that the calculation of a thresholded Pearson's correlation coefficient using only intensity values over a determined threshold in both channels produces numerical values that more accurately describe both synthetic datasets and biological examples. Its use will bring clarity and accuracy to colocalization studies using fluorescent microscopy.

Severe asthma with fungal sensitization: a case report and review of literature.

There is a substantial body of evidence supporting an association between asthma severity and fungal exposure and sensitization. Fungal allergens are a recognized risk factor for severe asthma. We describe the case of a 44-year-old asthmatic whose asthma control deteriorated after moving to a new flat with walls covered in mould. Allergic bronchopulmonary aspergillosis was excluded. Although sensitization to Candida was demonstrated by a positive Candida-specific radioallergosorbent test, the patient did not entirely satisfy the criteria for a diagnosis of allergic bronchopulmonary candidiasis. The patient's asthma control improved after engaging in a monthly washing regimen of the walls. This case further demonstrates the association between fungal sensitization and asthma severity. The term severe asthma with fungal sensitization has been recently coined to describe this phenomenon.

Quantization of widefield fluorescence images using structured illumination and image analysis software.

It is difficult to obtain precise quantitative measurements from fluorescent images captured from widefield microscopes. We wished to ascertain if reliable quantitative measurements of both biological and nonbiological specimens were possible using a widefield microscope equipped with a structured illumination system and image analysis software. In a nonbiological specimen, images were obtained from fluorescent beads of known intensity. For a biologically relevant model we used the uptake of fluorescently labeled transferrin by HeLa cells in culture. In the bead sample, the mean intensity of beads acquired with the structured illumination system showed relative intensities near to the predicted values without any further manipulation of data. In the transferrin uptake experiments, uptake and subsequent recycling of the labeled transferrin could be accurately and reproducibly measured. We conclude that using a combination of structured illumination and image processing algorithms accurate quantization of fluorescent images can be achieved in widefield microscopy.