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Objective: To derive a clinical prediction rule of termination of resuscitation (TOR) for out-of-hospital cardiac arrest (OHCA) with pre-hospital defibrillation given., Method: This was a retrospective multicenter cohort study performed in three emergency departments (EDs) of three regional hospitals from 1/1/2012 to 31/12/2018. Patients of OHCA aged ≥18 years old were included. Those with post-mortem changes, return of spontaneous circulation and receiving no resuscitation in EDs were excluded. A TOR rule was derived by logistic regression analysis based on demographics and end-tidal carbon dioxide level of included subjects with pre-hospital defibrillation given., Results: There were 447 included patients had received pre-hospital defibrillation, in which 148 had return of spontaneous circulation (ROSC), with 22 survived to discharge (STD). Independent predictors for death on or before ED arrival (no ROSC) included EMS call to ED time >20 min and ETCO2 level <20 mmHg from first three sets. A 2-criteria rule predicting death on or before ED arrival by fulfilling both of the independent predictors had a specificity of 0.95 (95% CI 0.90-0.98) and positive predictive value (PPV) of 0.95 (95% CI 0.90-0.98), if 2nd set of ETCO2 was used. The positive likelihood ratio was 10.04 (95% CI 4.83-20.89)., Conclusion: The 2-criteria TOR rule for OHCA patients with pre-hospital defibrillation had a high specificity and PPV for predicting death on or before ED arrival., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: It is a frequent challenge for physicians to identify pneumonia in patients with acute febrile respiratory symptoms, particularly in stable pediatric patients without respiratory distress. A decision rule is required to assist judgement on the need of ordering a chest radiograph., Method: This was a multicenter prospective study in 3 emergency departments. Children younger than 6 years old with an acute onset of fever and respiratory symptoms were recruited. Split sample method was adopted for derivation and validation of the Pediatric Acute Febrile Respiratory Illness rule (PAFRI Rule). PAFRI was derived from logistic regression with weighting based on adjusted odds ratios., Results: Out of 967 children evaluated, 530 had taken chest radiograph examination, with 91 demonstrated evidence of pneumonia on radiograph. PAFRI Rule was derived from logistic regression with 5 weighed predictors: duration of fever <3 days (0 points), 3-4 days (2 points), 5-6 days (4 points), ≥7 days (5 points), chills (2 points), nasal symptoms (-2 points), abnormal chest examination (3 points), SpO 2 ≤96% or tachypnea (3 points). The Area under ROC curve of the PAFRI Rule, the Bilkis Decision Rule and Bilkis Simpler Rule were 0.733, 0.600 and 0.579 respectively. A PAFRI score of ≥0 gives a sensitivity of 91.7% and negative predictive value of 97.7%., Conclusion: PAFRI rule can be used as a reference tool for guiding the need for taking Chest radiograph examination for pediatric patients. While promising, the PAFRI rule requires further validation., What's Known on This Subject: It is often a challenge for physicians to identify pneumonia in children acutely febrile with respiratory symptoms, particularly in those who are stable without respiratory distress. The decision to order chest radiograph was based on clinical assessment with heterogenous practice. A valid and verified clinical prediction rule for ordering chest radiograph examination for stable febrile children without signs of respiratory distress would therefore assist in management of this group of patients., What This Study Adds: The PAFRI rule, based on parameters from clinical bedside assessment, can be used as a reference tool for guiding the need for referral to emergency department or taking use of chest radiograph for pediatric patients, and triaging for higher priority of clinical care., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To derive a clinical prediction rule to predict pneumonia in patients with acute febrile respiratory illness to emergency departments., Method: This was a prospective multicentre study. 537 adults were recruited. Those requiring resuscitation or were hypoxaemic on presentation were excluded. Pneumonia was defined as new onset infiltrates on chest X-ray (CXR), or re-attendance within 7 days and diagnosed clinically as having pneumonia. A predictive model, the Acute Febrile Respiratory Illness (AFRI) rule was derived by logistic regression analysis based on clinical parameters. The AFRI rule was internally validated with bootstrap resampling and was compared with the Diehr and Heckerling rule., Results: In the 363 patients who underwent CXR, 100 had CXR confirmed pneumonia. There were 7 weighted factors within the ARFI rule, which on summation, gave the AFRI score: age ≥ 65 (1 point), peak temperature within 24 h ≥ 40 °C (2 points), fever duration ≥3 days (2 points), sore throat (-2 points), abnormal breath sounds (1 point), history of pneumonia (1 point) and SpO2 ≤ 96% (1 point). With the bootstrap resampling, the AFRI rule was found to be more accurate than the Diehr and Heckerling rule (area under ROC curve 0.816, 0.721 and 0.566 respectively, p < 0.001). At a cut-off of AFRI≥0, the rule was found to have 95% sensitivity, with a negative predictive value of 97.2%. Using the AFRI score, we found CXR could be avoided for patients having a score of <0., Conclusion: AFRI score could assist emergency physicians in identifying pneumonia patients among all adult patients presented to ED for acute febrile respiratory illness., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virus in vitro and in a lethal mouse model. Our data demonstrated that sera from the E1-vaccinated mice could induce high ADCC activities. Importantly, the induction of ADCC response modestly decreased viral load in the lungs of H1N1-infected mice. However, the elevated ADCC significantly increased mouse alveolar damage and mortality than that of the PBS-vaccinated group ( P  < 0.0001). The phenotype was potentially due to an exaggerated inflammatory cell infiltration triggered by ADCC, as an upregulated release of cytotoxic granules (perforin) was observed in the lung tissue of E1-vaccinated mice after H1N1 influenza virus challenge. Overall, our data suggested that ADCC elicited by certain domains of HA head region might have a detrimental rather than protective effect during influenza virus infection. Thus, future design of universal influenza vaccine shall strike a balance between the induction of protective immunity and potential side effects of ADCC.

The efficacy of traditional Chinese medicine (TCM) treatments for Western medicine (WM) diseases relies heavily on the proper classification of patients into TCM syndrome types. The authors developed a data-driven method for solving the classification problem, where syndrome types were identified and quantified based on statistical patterns detected in unlabeled symptom survey data. The new method is a generalization of latent class analysis (LCA), which has been widely applied in WM research to solve a similar problem, i.e., to identify subtypes of a patient population in the absence of a gold standard. A well-known weakness of LCA is that it makes an unrealistically strong independence assumption. The authors relaxed the assumption by first detecting symptom co-occurrence patterns from survey data and used those statistical patterns instead of the symptoms as features for LCA. This new method consists of six steps: data collection, symptom co-occurrence pattern discovery, statistical pattern interpretation, syndrome identification, syndrome type identification and syndrome type classification. A software package called Lantern has been developed to support the application of the method. The method was illustrated using a data set on vascular mild cognitive impairment.

Introduction: There are two antivenoms that may be administered in Hong Kong following a bite by Trimeresurus albolabris: the green pit viper antivenom from the Thai Red Cross Society in Thailand and the Agkistrodon halys antivenom from the Shanghai Institute of Biological Products in China. Both are recommended by the Central Coordinating Committee of Accident and Emergency Services of the Hospital Authority for treating patients with a bite by Trimeresurus albolabris. The choice of which antivenom to use is based on physician preference. This study aimed to compare the relative efficacy of the two antivenoms., Methods: This in-vitro experimental study was carried out by a wildlife conservation organisation and a regional hospital in Hong Kong. Human plasma from 40 adult health care worker volunteers was collected. The Trimeresurus albolabris venom was added to human plasma and the mixture was assayed after incubation with each antivenom (green pit viper and Agkistrodon halys) using saline as a control. Fibrinogen level and clotting time in both antivenom groups were studied., Results: The mean fibrinogen level was elevated from 0 g/L to 2.86 g/L and 1.11 g/L after the addition of green pit viper antivenom and Agkistrodon halys antivenom, respectively. When mean clotting time was measured, the value was 6.70 minutes in the control, prolonged to more than 360 minutes by green pit viper antivenom and to 19.06 minutes by Agkistrodon halys antivenom., Conclusions: Green pit viper antivenom was superior to Agkistrodon halys antivenom in neutralisation of the thrombin-like and hypofibrinogenaemic activities of Trimeresurus albolabris venom.

Objective: To evaluate the diagnostic accuracy of an abrupt and sustained increase in end-tidal carbon dioxide (ETCO2) to indicate return of spontaneous circulation (ROSC) during resuscitation of patient with out-of-hospital cardiac arrest., Design: Cross-sectional study., Setting: Emergency department of two regional hospitals., Methods: Patients with age ≥18 years old, suffered non-traumatic out-of-hospital cardiac arrest with active resuscitation and endotracheal intubation performed in emergency department, were included. ETCO2 value was charted throughout resuscitation. Time of ROSC was remarked. ETCO2 levels before and after ROSC were compared. Diagnostic accuracy of ETCO2 rise ≥10mmHg, ETCO2 rise ≥20mmHg, and ETCO2 rise to the level ≥40mmHg were evaluated for indicating ROSC., Results: ETCO2 level immediately after ROSC was higher as compared to the value before return of circulation (median ETCO2 was 32mmHg and 41mmHg respectively, p=0.033). With ETCO2 rise ≥10mmHg, the sensitivity was low (33%, 95% CI 22-47%), while specificity was 97% (95% CI 91-99%). Positive and negative predictive values were 83% (95% CI 62-95%) and 74% (95% CI 66-81%) respectively. The diagnostic accuracy was higher in cardiac arrest with presumed non-cardiac etiology (sensitivity 45%, specificity 100%) as compared to those with cardiac etiology (sensitivity 18%, specificity 97%)., Conclusions: The feature of an abrupt rise of ETCO2 was a specific but non-sensitive marker of ROSC in patient with out-of-hospital cardiac arrest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the role of initial ETCO2 value in prognostication of OHCA patients in an Asian-Chinese cohort., Design: Prospective cohort study., Setting: Emergency departments of two regional hospitals in a cluster of Hong Kong., Patients: Patients were recruited prospectively from the local cardiac arrest registry from July 2012 to June 2013. Patients of non traumatic OHCA aged ≥18 years old were included. Patients of OHCA presented with postmortem changes, those who decided for Do Not Resuscitate (DNR), regained pulse before arrival, or those without proper documentation of ETCO2 would be excluded., Outcome: Primary outcome was return of spontaneous circulation (ROSC)., Results: A 3-min ETCO2 >10mmHg was a predictor of ROSC with OR 18.16 (95% CI 4.79-51.32, p<0.001). The diagnostic accuracy of 3-min ETCO2 >10mmHg to predict ROSC: sensitivity was 0.95 (95% CI 0.89-0.98) while the specificity was 0.27 (95% CI 0.21-0.33). Positive predictive value was 0.40 (95% CI 0.34-0.46) while negative predictive value (NPV) was 0.92 (95% CI 0.82-0.97). Area under ROC curve of 3-min ETCO2 predicting ROSC was 0.80 (95% CI 0.71-0.91)., Conclusions: A 3-min ETCO2 ≤10mmHg was associated with poor prognosis and low chance of ROSC. Low ETCO2 level may have a role to reduce prolonged medically futile resuscitation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. Combination of MERS-4 and MERS-27 demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. Biochemical analysis indicated that MERS-4 and MERS-27 blocked RBD interaction with DPP4 on the cell surface. MERS-4, in particular, bound soluble RBD with an about 45-fold higher affinity than DPP4. Mutagenesis analysis suggested that MERS-4 and MERS-27 recognized distinct regions in RBD. These results suggest that MERS-4 and MERS-27 are RBD-specific potent inhibitors and could serve as promising candidates for prophylactic and therapeutic interventions against MERS-CoV infection.

1. There is no effective anti-H5N1 avian influenza agent. 2. A chemical compound— BFDBSC—can inhibit H5N1 virus infection in cell cultures, and such inhibition might be attributable to its halogenated benzoyl residues. 3. This pilot study assessed anti- H5N1 activity and toxicity of four chemical compounds with halogenated benzoyl residues in cell culture system. 4. Two compounds—FPBFDBSC and BFB-gallate— showed higher antiviral effectsthan BFDBSC, whearas the other two—BFB-borneol and BFB-menthol—showed lower antiviral effects. These compounds did not show toxicity. 5. The halogenated benzoyl residues may play a key role in anti-H5N1 effects. However, all these compounds showed poor solubility, which may limit their utility

To reveal the putative cellular factors involved in SARS coronavirus replication, the helicase (Hel, nsp13) of SARS coronavirus was used to screen the cDNA library of rat pulmonary epithelial cells using the yeast two-hybrid system. Positively interacting proteins were further tested using a mammalian cell hybrid system and co-immunoprecipitation in the human A549 cell line, which has been shown to support SARS coronavirus replication. Out of the seven positive clones observed by yeast two-hybrid assay, only the Ddx5 (Asp-Glu-Ala-Asp box polypeptide 5) protein showed specific interaction with SARS-CoV helicase. When expression of DdX5 was knocked down by small interfering RNA (siRNA), SARS coronavirus replication was significantly inhibited in fetal rhesus kidney (FRhK-4) cells. Since Ddx5 is a multifunctional protein that plays important roles in transcriptional regulation, its interaction with SARS coronavirus helicase provides interesting clues for studying virus-host cell interactions in SARS-CoV infections.

A single-chain antibody fragment (scFv) was constructed from a hybridoma antibody that binds to phosphorylcholine (PC) only when this hapten is presented in the form of the immunizing antigen (derived from Trichinella) but not when it is presented on other carriers (as found, for example, in pneumococcal capsules). The scFv derivative was found to lack this carrier specificity as it bound indiscriminately, but specifically, to the various PC-associated antigens, and exhibits a two-fold lower affinity (3.5x10(5)M(-1)) for nitrophenyl-PC than the native antibody. The findings suggest that the scFv combining site is different in fine structure from that of the native antibody.

Operative treatment is indicated in displaced intra-articular glenoid fractures. We report the results of treating 14 such fractures with open reduction and stable internal fixation. With an average follow-up period of 30.5 months, all fractures healed. All shoulders are rated good according to Rowe's scoring system. Complication was minimal, apart from those which resulted from the concomitant chest injuries. We therefore conclude that the operative treatment for these fractures gives good and predictable results. Special attention should be paid to treat the complications resulting from the common association of chest injuries in these patients.