Early Exclusion of Major Adverse Cardiac Events in Emergency Department Chest Pain Patients: A Prospective Observational Study.

BACKGROUND: The current evaluation of patients with chest pain presenting to an emergency department (ED) with suspected acute coronary syndrome (ACS) is a lengthy process involving serial measurements of troponin. OBJECTIVE: We aimed to validate the diagnostic accuracy of a Thrombolysis in Myocardial Infarction (TIMI) score with single high-sensitive cardiac troponin T (hs-cTnT) for early rule out of 30-day major adverse cardiac events (MACE), and to compare the TIMI score with combinations of heart-type fatty acid binding protein (H-FABP) and a modified HEART (history, electrocardiogram, age, risk factors, troponin) score. METHODS: We recruited 602 consecutive adult patients with chest pain and suspected ACS in the ED. Each patient had TIMI and HEART scores, and a point-of-care H-FABP test. RESULTS: MACE occurred in 42 (7.0%) patients within 30 days. A low risk for 30-day MACE was identified by a modified TIMI score of 0 in 65 (11%) patients, and by a HEART score ≤ 2 in 96 (16%) patients. No MACE occurred in these groups, giving both scores a sensitivity of 100% (95% confidence interval [CI] 91.6-100%), and specificity of 11.6% (95% CI 9.2-14.5%) and 17.1% (95% CI 14.2-20.5%), respectively. Use of combined TIMI and HEART scores improved the specificity further to 22.0% (95% CI 18.7-25.6%) without lowering sensitivity. Early H-FABP measurement > 7 µg/L had a sensitivity of 41.5% (95% CI 27.8-56.6%) and a specificity of 91.1% (95% CI 88.4-93.2%) for predicting 30-day MACE. CONCLUSIONS: A modified TIMI score of 0 or a HEART score of ≤ 2, incorporating a single hs-cTnT level, will identify patients with low risk of 30-day MACE for early discharge within 2 h of ED arrival.

Return to work after injury in Hong Kong: prospective multi-center cohort study.

PURPOSE: Trauma remains a major cause of morbidity and disability worldwide; however, reliable data on the health status of an urban Asian population after injury are scarce. The aim was to evaluate 1-year post-trauma return to work (RTW) status in Hong Kong. METHODS: This was a prospective, multi-center cohort study involving four regional trauma centers from 2017 to 2019 in Hong Kong. Participants included adult patients entered into the trauma registry who were working or seeking employment at the time of injury. The primary outcome was the RTW status up to 1 year. The Extended Glasgow Outcome Scale, 12-item Short Form (SF-12) survey and EQ5D were also obtained during 1-, 3-, 6-, 9-, and 12-month follow-ups. Multivariable Cox proportional hazards regression analysis was used for analysis. RESULTS: Six hundred and seven of the 1115 (54%) recruited patients had RTW during the first year after injury. Lower physical requirements (p = 0.003, HR 1.51) in pre-injury job nature, higher educational levels (p < 0.001, HR 1.95), non-work-related injuries (p < 0.001, HR 1.85), shorter hospital length of stay (p = 0.007, HR 0.98), no requirement for surgery (p = 0.006, HR 1.34), and patients who could be discharged home (p = 0.006, HR 1.43) were associated with RTW within 12 months post-injury. In addition, 1-month outcomes including extended Glasgow Outcome Scale ≥ 6 (p = 0.001, HR 7.34), higher mean SF-12 physical component summary (p = 0.002, HR 1.02) and mental component summary (p < 0.001, HR 1.03), and higher EQ5D health index (p = 0.018, HR 2.14) were strongly associated with RTW. CONCLUSIONS: We have identified factors associated with failure to RTW during the first year following in Hong Kong including socioeconomic factors, injury factors and treatment-related factors and 1-month outcomes. Future studies should focus on the interventions that can impact on RTW outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03219424.

CNGA2 channels mediate adenosine-induced Ca2+ influx in vascular endothelial cells.

OBJECTIVE: Adenosine is a cAMP-elevating vasodilator that induces both endothelium-dependent and -independent vasorelaxation. An increase in cytosolic Ca(2+) ([Ca(2+)](i)) is a crucial early signal in the endothelium-dependent relaxation elicited by adenosine. This study explored the molecular identity of channels that mediate adenosine-induced Ca(2+) influx in vascular endothelial cells. METHODS AND RESULTS: Adenosine-induced Ca(2+) influx was markedly reduced by L-cis-diltiazem and LY-83583, two selective inhibitors for cyclic nucleotide-gated (CNG) channels, in H5V endothelial cells and primary cultured bovine aortic endothelial cells (BAECs). The Ca(2+) influx was also inhibited by 2 adenylyl cyclase inhibitors MDL-12330A and SQ-22536, and by 2 A(2B) receptor inhibitors MRS-1754 and 8-SPT, but not by an A(2A) receptor inhibitor SCH-58261 or a guanylyl cyclase inhibitor ODQ. Patch clamp experiments recorded an adenosine-induced current that could be inhibited by L-cis-diltiazem and LY-83583. A CNGA2-specific siRNA markedly decreased the Ca(2+) influx and the cation current in H5V cells. Furthermore, L-cis-diltiazem inhibited the endothelial Ca(2+) influx in mouse aortic strips, and it also reduced 5-N-ethylcarboxamidoadenosine (NECA, an A(2) adenosine receptor agonist)-induced vasorelaxation. CONCLUSIONS: CNGA2 channels play a key role in adenosine-induced endothelial Ca(2+) influx and vasorelaxation. It is likely that adenosine acts through A(2B) receptors and adenylyl cyclases to stimulate CNGA2.

Epinephrine-induced Ca2+ influx in vascular endothelial cells is mediated by CNGA2 channels.

Epinephrine, through its action on beta-adrenoceptors, may induce endothelium-dependent vascular dilation, and this action is partly mediated by a cytosolic Ca(2+) ([Ca(2+)](i)) change in endothelial cells. In the present study, we explored the molecular identity of the channels that mediate epinephrine-induced endothelial Ca(2+) influx and subsequent vascular relaxation. Patch clamp recorded an epinephrine- and cAMP-activated cation current in the primary cultured bovine aortic endothelial cells (BAECs) and H5V endothelial cells. L-cis-diltiazem and LY-83583, two selective inhibitors for cyclic nucleotide-gated channels, diminished this cation current. Furthermore, this cation current was greatly reduced by a CNGA2-specific siRNA in H5V cells. With the use of fluorescent Ca(2+) dye, it was found that epinephrine and isoprenaline, a beta-adrenoceptor agonist, induced endothelial Ca(2+) influx in the presence of bradykinin. This Ca(2+) influx was inhibited by L-cis-diltiazem and LY-83583, and by a beta(2)-adrenoceptor antagonist ICI-118551. CNGA2-specific siRNA also diminished this Ca(2+) influx in H5V cells. Furthermore, L-cis-diltiazem and LY-83583 inhibited the endothelial Ca(2+) influx in isolated mouse aortic strips. L-cis-diltiazem also markedly reduced the endothelium-dependent vascular dilation to isoprenaline in isolated mouse aortic segments. In summary, CNG channels, CNGA2 in particular, mediate beta-adrenoceptor agonist-induced endothelial Ca(2+) influx and subsequent vascular dilation.

Oral paracetamol and/or ibuprofen for treating pain after soft tissue injuries: Single centre double-blind, randomised controlled clinical trial.

BACKGROUND: Soft tissue injuries commonly present to the emergency department (ED), often with acute pain. They cause significant suffering and morbidity if not adequately treated. Paracetamol and ibuprofen are commonly used analgesics, but it remains unknown if either one or the combination of both is superior for pain control. OBJECTIVES: To investigate the analgesic effect of paracetamol, ibuprofen and the combination of both in the treatment of soft tissue injury in an ED, and the side effect profile of these drugs. METHODS: Double-blind, double dummy, placebo-controlled randomised controlled trial. 782 adult patients presenting with soft tissue injury without obvious fractures attending the ED of a university hospital in the New Territories of Hong Kong were recruited. Patients were randomised using a random number table into three parallel arms of paracetamol only, ibuprofen only and a combination of paracetamol and ibuprofen in a 1:1:1 ratio. The primary outcome measure was pain score at rest and on activity in the first 2 hours and first 3 days. Data was analysed on an intention to treat basis. RESULTS: There was no statistically significant difference in pain score in the initial two hours between the three groups, and no clinically significant difference in pain score in the first three days. CONCLUSION: There was no difference in analgesic effects or side effects observed using oral paracetamol, ibuprofen or a combination of both in patients with mild to moderate pain after soft tissue injuries attending the ED. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (no. NCT00528658).

Acute appendicitis in adults: Diagnostic accuracy of emergency doctors in a university hospital in Hong Kong.

OBJECTIVE: The aim of this study was to assess the diagnostic accuracy of ED doctors with variable training levels in detecting acute appendicitis, without access to advanced imaging in admitted patients with acute abdominal pain in a university hospital of Hong Kong. METHODS: A retrospective analysis was performed on data collected from prospectively identified patients presenting to the ED with acute abdominal pain and admitted to either a surgical or emergency medical ward between December 2011 and October 2012. Their ED diagnoses with regard to acute appendicitis status were compared with their final diagnoses on discharge from hospital. The gold standard was a histopathological diagnosis of acute appendicitis. The diagnostic accuracy was compared against that generally achieved by computed tomography (CT) scanning in other studies (93-98%), the best diagnostic test currently available for acute appendicitis. A good diagnostic test should have an overall accuracy rate of at least 95%. RESULTS: A total of 1653 patients were included in the study. The sensitivity, specificity, positive predictive value and negative predictive value of ED physicians' diagnosis of acute appendicitis were 81% (73-87%), 84% (82-86%), 31% (28-34%) and 98% (97-99%), respectively, giving an overall diagnostic accuracy of 84% (82-85%). The overall accuracy for separate female and male cohorts were 79% (76-82%) and 89% (83-91%), respectively. CONCLUSIONS: Diagnostic accuracy of emergency doctors with variable training levels and no access to advanced imaging in a Hong Kong hospital in detecting appendicitis in patients with acute abdominal pain is higher in male patients than in female patients, but lower than that achieved by CT scanning.

Plasma miR-124-3p and miR-16 concentrations as prognostic markers in acute stroke.

OBJECTIVES: This study aimed to investigate plasma concentrations of miR-124-3p and miR-16 as prognostic markers in emergency department patients with acute stroke. DESIGN AND METHODS: Plasma concentrations of miR-124-3p and miR-16 of 84 stroke patients (presenting to the emergency department within 24h from onset of symptoms) were determined by RT-qPCR. The primary outcome measure was 3-month mortality and the secondary outcome measure was post-stroke modified Rankin Score (mRS). RESULTS: Twelve patients (14.3%) died within 3months of hospital admission and forty-one (48.8%) patients as achieved a 3-month mRS>2. Median plasma miR-124-3p concentrations were elevated in patients who died compared to patients who survived (p=0.0052), and its levels were found to be higher in patients with a 3-month mRS>2 compared with patients with mRS≤2 (p=0.0312). Higher plasma miR-16 concentrations were observed in patients who survived than in patients who died (p=0.0394), while its concentrations were lower in patients achieving mRS>2 than in patients with mRS≤2 (p=0.0124). For a subgroup of cases presenting to the emergency department within 6h from time of symptom onset (n=36), plasma miR-124-3p concentrations predicted 3-month mortality with an area under the ROC curve of 0.87 (95%CI: 0.72-0.96). CONCLUSIONS: Plasma miR-124-3p and miR-16 are molecular markers which could be useful for the early prediction of mortality and mRS.

Learning profiles for noninvasive transcutaneous Doppler ultrasound.

OBJECTIVE: This study aimed to establish learning profiles for noninvasive transcutaneous Doppler ultrasound. MATERIALS AND METHODS: Four trainees attended a 2-h lecture, followed by a 15-min demonstration on a volunteer and a 30-min hands-on workshop in a small group setting. Then, they underwent hands-on practice on 50 participants without supervision. The skill acquisitions in terms of signal magnitude, signal quality, and measurement time of the trainees were evaluated through 50 assessments, and were compared with that of a trainer with extensive experience on the use of an ultrasonic cardiac output monitor acting as a 'gold standard'. The learning profile for each individual trainee was analyzed using the cumulative sum graphical method. RESULTS: Four trainees performed ultrasonic cardiac output monitor on 50 participants. All trainees attained proficiency after 18-36 assessments to achieve aortic signal magnitude and quality comparable with the trainer. It requires a minimum of nine assessments to obtain three aortic scans within 5 min with 95% success rates. Only half of the trainees achieved competence in pulmonary scans and the minimum number of assessments required was 36. A minimum of 22 assessments were required for three pulmonary scans within 10 min with 95% success rates. CONCLUSION: A substantial period of learning needs to be undertaken to achieve proficiency on the use of noninvasive transcutaneous Doppler ultrasound. Cumulative sum analysis is a useful tool for ongoing quality assessment during medical education and training in practical procedures on an individual basis.

Evaluation of the Recognition of Stroke in the Emergency Room (ROSIER) scale in Chinese patients in Hong Kong.

BACKGROUND AND PURPOSE: The objective of this study was to determine the performance of the Recognition Of Stroke In the Emergency Room (ROSIER) scale in risk-stratifying Chinese patients with suspected stroke in Hong Kong. METHODS: This was a prospective cohort study in an urban academic emergency department (ED) over a 7-month period. Patients over 18 years of age with suspected stroke were recruited between June 2011 and December 2011. ROSIER scale assessment was performed in the ED triage area. Logistic regression analysis was used to estimate the impacts of diagnostic variables, including ROSIER scale, past history and ED characteristics. FINDINGS: 715 suspected stroke patients were recruited for assessment, of whom 371 (52%) had acute cerebrovascular disease (302 ischaemic strokes, 24 transient ischaemic attacks (TIA), 45 intracerebral haemorrhages), and 344 (48%) had other illnesses i.e. stroke mimics. Common stroke mimics were spinal neuropathy, dementia, labyrinthitis and sepsis. The suggested cut-off score of>0 for the ROSIER scale for stroke diagnosis gave a sensitivity of 87% (95%CI 83-90), a specificity of 41% (95%CI 36-47), a positive predictive value of 62% (95%CI 57-66), and a negative predictive value of 75% (95%CI 68-81), and the AUC was 0.723. The overall accuracy at cut off>0 was 65% i.e. (323+141)/715. INTERPRETATION: The ROSIER scale was not as effective at differentiating acute stroke from stroke mimics in Chinese patients in Hong Kong as it was in the original studies, primarily due to a much lower specificity. If the ROSIER scale is to be clinically useful in Chinese suspected stroke patients, it requires further refinement.

Comparison of miR-124-3p and miR-16 for early diagnosis of hemorrhagic and ischemic stroke.

BACKGROUND: The present study aimed to investigate and compare plasma concentrations of miR-124-3p and miR-16 as diagnostic markers in acute stroke. METHODS: miR-124-3p and miR-16 concentrations in 93 stroke patients were analyzed using real-time polymerase chain reaction. The primary outcome was the differentiation of hemorrhagic and ischemic stroke. RESULTS: Of 93 patients, 74 (79.6%) were diagnosed as ischemic stroke (IS) and 19 (20.4%) were diagnosed as hemorrhagic stroke (HS). Median plasma 124-3p concentrations taken within 24h of symptom onset were higher in HS patients than that in IS patients (3.8×10(5) vs 2.0×10(5) copies/ml plasma, p=0.0109), while median miR-16 concentration in IS patients were higher than that in HS patients (1.6×10(9) vs 1.3×10(9) copies/ml plasma, p=0.0399). The odds ratio (OR) for discriminating HS and IS with miR-124-3p and miR-16 was 5.37 and 9.75 respectively. CONCLUSION: Both miR-124-3p and miR-16 are diagnostic markers to discriminate HS and IS.

Cyclic nucleotide-gated channels contribute to thromboxane A2-induced contraction of rat small mesenteric arteries.

BACKGROUND: Thromboxane A(2) (TxA(2))-induced smooth muscle contraction has been implicated in cardiovascular, renal and respiratory diseases. This contraction can be partly attributed to TxA(2)-induced Ca(2+) influx, which resulted in vascular contraction via Ca(2+)-calmodulin-MLCK pathway. This study aims to identify the channels that mediate TxA(2)-induced Ca(2+) influx in vascular smooth muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: Application of U-46619, a thromboxane A(2) mimic, resulted in a constriction in endothelium-denuded small mesenteric artery segments. The constriction relies on the presence of extracellular Ca(2+), because removal of extracellular Ca(2+) abolished the constriction. This constriction was partially inhibited by an L-type Ca(2+) channel inhibitor nifedipine (0.5-1 microM). The remaining component was inhibited by L-cis-diltiazem, a selective inhibitor for CNG channels, in a dose-dependent manner. Another CNG channel blocker LY83583 [6-(phenylamino)-5,8-quinolinedione] had similar effect. In the primary cultured smooth muscle cells derived from rat aorta, application of U46619 (100 nM) induced a rise in cytosolic Ca(2+) ([Ca(2+)](i)), which was inhibited by L-cis-diltiazem. Immunoblot experiments confirmed the presence of CNGA2 protein in vascular smooth muscle cells. CONCLUSIONS/SIGNIFICANCE: These data suggest a functional role of CNG channels in U-46619-induced Ca(2+) influx and contraction of smooth muscle cells.

TRPC3 is involved in flow- and bradykinin-induced vasodilation in rat small mesenteric arteries.

AIM: To test the possible involvement of TRPC3 in agonist-induced relaxation and flow-induced vasodilation in rat small mesenteric arteries. METHODS: Male Sprague-Dawley rats were used in the present study. After 72 h-treatment of antisense oligo via tail vein injection, isometric tension and isobaric diameter measurement were carried out with isolated mesenteric artery segments by using either a Pressure Myograph or a Multi Myograph system. Endothelial [Ca(2+)]i changes were measured with a MetaFluor imaging system in response to flow or to 30 nmol/L bradykinin. RESULTS: Immunohistochemical study showed that the 72 h-treatment of antisense oligo via tail vein injection markedly decreased the TRPC3 expression in mesenteric arteries, indicating the effectiveness of the antisense oligo. Isometric tension and isobaric diameter measurement showed that, although the antisense oligo treatment did not affect histamine-, ATP-, and CPA-induced relaxation, it did reduce the magnitude of flow-induced vasodilation by approximately 13% and decreased bradykinin-induced vascular relaxation with its EC50 value raised by nearly 3-fold. Endothelial [Ca(2+)]i measurement revealed that treatment of the arteries with antisense oligos significantly attenuated the magnitude of endothelial [Ca(2+)]i rise in response to flow and to 30 nmol/L bradykinin. CONCLUSION: The results suggest that TRPC3 is involved in flow- and bradykinin-induced vasodilation in rat small mesenteric arteries probably by mediating the Ca(2+) influx into endothelial cells.