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Background: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain. We investigated whether an early rule-out pathway is safe and effective for patients with suspected acute coronary syndrome., Methods: We performed a stepped-wedge cluster randomized controlled trial in the emergency departments of 7 acute care hospitals in Scotland. Consecutive patients presenting with suspected acute coronary syndrome between December 2014 and December 2016 were included. Sites were randomized to implement an early rule-out pathway where myocardial infarction was excluded if high-sensitivity cardiac troponin I concentrations were <5 ng/L at presentation. During a previous validation phase, myocardial infarction was ruled out when troponin concentrations were <99th percentile at 6 to 12 hours after symptom onset. The coprimary outcome was length of stay (efficacy) and myocardial infarction or cardiac death after discharge at 30 days (safety). Patients were followed for 1 year to evaluate safety and other secondary outcomes., Results: We enrolled 31 492 patients (59±17 years of age [mean±SD]; 45% women) with troponin concentrations <99th percentile at presentation. Length of stay was reduced from 10.1±4.1 to 6.8±3.9 hours (adjusted geometric mean ratio, 0.78 [95% CI, 0.73-0.83]; P <0.001) after implementation and the proportion of patients discharged increased from 50% to 71% (adjusted odds ratio, 1.59 [95% CI, 1.45-1.75]). Noninferiority was not demonstrated for the 30-day safety outcome (upper limit of 1-sided 95% CI for adjusted risk difference, 0.70% [noninferiority margin 0.50%]; P =0.068), but the observed differences favored the early rule-out pathway (0.4% [57/14 700] versus 0.3% [56/16 792]). At 1 year, the safety outcome occurred in 2.7% (396/14 700) and 1.8% (307/16 792) of patients before and after implementation (adjusted odds ratio, 1.02 [95% CI, 0.74-1.40]; P =0.894), and there were no differences in hospital reattendance or all-cause mortality., Conclusions: Implementation of an early rule-out pathway for myocardial infarction reduced length of stay and hospital admission. Although noninferiority for the safety outcome was not demonstrated at 30 days, there was no increase in cardiac events at 1 year. Adoption of this pathway would have major benefits for patients and health care providers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03005158.

Background: The introduction of more sensitive cardiac troponin assays has led to increased recognition of myocardial injury in acute illnesses other than acute coronary syndrome. The Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin testing and classification of patients with myocardial injury based on pathogenesis, but the clinical implications of implementing this guideline are not well understood., Methods: In a stepped-wedge cluster randomized, controlled trial, we implemented a high-sensitivity cardiac troponin assay and the recommendations of the Universal Definition in 48 282 consecutive patients with suspected acute coronary syndrome. In a prespecified secondary analysis, we compared the primary outcome of myocardial infarction or cardiovascular death and secondary outcome of noncardiovascular death at 1 year across diagnostic categories., Results: Implementation increased the diagnosis of type 1 myocardial infarction by 11% (510/4471), type 2 myocardial infarction by 22% (205/916), and acute and chronic myocardial injury by 36% (443/1233) and 43% (389/898), respectively. Compared with those without myocardial injury, the rate of the primary outcome was highest in those with type 1 myocardial infarction (cause-specific hazard ratio [HR] 5.64 [95% CI, 5.12-6.22]), but was similar across diagnostic categories, whereas noncardiovascular deaths were highest in those with acute myocardial injury (cause specific HR 2.65 [95% CI, 2.33-3.01]). Despite modest increases in antiplatelet therapy and coronary revascularization after implementation in patients with type 1 myocardial infarction, the primary outcome was unchanged (cause specific HR 1.00 [95% CI, 0.82-1.21]). Increased recognition of type 2 myocardial infarction and myocardial injury did not lead to changes in investigation, treatment or outcomes., Conclusions: Implementation of high-sensitivity cardiac troponin assays and the recommendations of the Universal Definition of Myocardial Infarction identified patients at high-risk of cardiovascular and noncardiovascular events but was not associated with consistent increases in treatment or improved outcomes. Trials of secondary prevention are urgently required to determine whether this risk is modifiable in patients without type 1 myocardial infarction., Clinical Trial Registration: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

Background: Guidelines acknowledge the emerging role of high-sensitivity cardiac troponin (hs-cTnl) for risk stratification and the early rule-out of myocardial infarction, but multiple thresholds have been described. We evaluate the safety and effectiveness of risk stratification thresholds in patients with suspected acute coronary syndrome., Methods: Consecutive patients with suspected acute coronary syndrome (n=48 282) were enrolled in a multicenter trial across 10 hospitals in Scotland. In a prespecified secondary and observational analysis, we compared the performance of the limit of detection (<2 ng/L) and an optimized risk stratification threshold (<5 ng/L) using the Abbott high-sensitivity troponin I assay. Patients with myocardial injury at presentation, with ≤2 hours of symptoms or with ST-segment elevation myocardial infarction were excluded. The negative predictive value was determined in all patients and in subgroups for a primary outcome of myocardial infarction or cardiac death within 30 days. The secondary outcome was myocardial infarction or cardiac death at 12 months, with risk modeled using logistic regression adjusted for age and sex., Results: In total, 32 837 consecutive patients (61±17 years, 47% female) were included, of whom 23 260 (71%) and 12,716 (39%) had hs-cTnl concentrations of <5 ng/L and <2 ng/L at presentation. The negative predictive value for the primary outcome was 99.8% (95% CI, 99.7%-99.8%) and 99.9% (95% CI, 99.8%-99.9%) in those with hs-cTnl concentrations of <5 ng/L and <2 ng/L, respectively. At both thresholds, the negative predictive value was consistent in men and women and across all age groups, although the proportion of patients identified as low risk fell with increasing age. Compared with patients with hs-cTnl concentrations of ≥5 ng/L but <99th centile, the risk of myocardial infarction or cardiac death at 12 months was 77% lower in those <5 ng/L (5.3% vs 0.7%; adjusted odds ratio, 0.23 [95% CI, 0.19-0.28]) and 80% lower in those <2 ng/L (5.3% vs 0.3%; adjusted odds ratio, 0.20 [95% CI, 0.14-0.29])., Conclusions: Use of risk stratification thresholds for hs-cTnl identify patients with suspected acute coronary syndrome and at least 2 hours of symptoms as low risk at presentation irrespective of age and sex., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

Objectives: We describe a way of using Taylor spatial frames (TSFs) for acute deformation of Gustilo IIIB tibial fractures and infected tibial nonunions to close the soft tissue defects and to gradually restore anatomical alignment. We use the Direct Scheduler Utility module of the web-based software for TSFs to successfully restore the anatomical alignment., Design: We report a case series of the above technique., Setting: Care was carried out at a tertiary referral center for limb reconstruction., Patients: Seven consecutive patients with significant soft tissue loss after tibial fractures were treated., Intervention: Defects were closed with acute deformation of the fracture followed by gradual correction to anatomical alignment with a 2-ring TSF., Main Outcome Measurement: Successful closure of the soft tissue defect was our primary outcome measure., Results: Soft tissue defects ranged from 3 to 10 cm. All healed without additional plastic surgery to cover the exposed tibia. Only 1 patient required an additional TSF prescription to achieve anatomical alignment., Conclusions: The use of the Direct Scheduler module of the web-based TSF software allows the complete correction of complex deformities without the need for obtaining complex mounting and frame parameters. We achieved successful closure of soft tissue defects and restored the anatomical tibial alignment in all our cases.

Study Design: Case report., Objective: We present a case of myositis ossificans (MO) of the upper cervical spine in a young child. The literature is reviewed with the classification, etiology, and treatment of MO discussed., Summary of Background Data: Calcification of joint capsule, muscle, cartilage, and ligaments is a well-known phenomenon and is known as myositis ossificans. It is very rarely seen in the head and neck, with no reports of MO of the soft tissues surrounding the first 2 cervical vertebrae., Methods: An 8-year-old boy presented with severe neck pain after a fall. He had had a similar neck injury 4 years before, but made a full recovery. Radiographs showed a large ossified lesion between the posterior elements of C1 and C2. After further imaging, a diagnosis of MO was made., Results: The child was treated with simple analgesia and observation. With no evidence of neurologic compromise and minimal symptoms, there was no indication for surgical intervention., Conclusion: Although rare, MO should be suspected as one of the possible causes of persistent pain following cervical spine injury in children. We would advise a low threshold for cervical spine imaging in the child presenting with persistent neck pain and stiffness, even years after injury.

Purpose: Successful limbal allotransplantation allows regression of limbal stem cell deficiency features. Transplant survival is presumed if clinical improvement occurs. However, positive proof of surviving transplanted stem cells remains difficult. This follow-up study attempted to prove donor cell survival 5 years after limbal stem cell allograft in one woman with aniridia., Methods: Impression cytology and single-cell DNA fingerprinting were used to investigate a previously studied patient. Corneal epithelial cells were harvested from five sites and isolated by micromanipulation. Polymerase chain reaction and short tandem repeat profiling were used to obtain forensic standard "DNA fingerprints" from single cells. (The technique is described in the preceding article, Part I.) Blood samples yielded host and donor DNA for comparison. Negative controls were performed for impression cytology and polymerase chain reaction. Simultaneous micro-scrape samples were also taken., Results: Impression cytology samples permitted informative DNA fingerprints from all corneal sites and represented 76% (23/30) of tested cells. Fifty percent (15/30) of the fingerprints were "specific" but 83% (19/23) matched the host DNA fingerprint. The remaining 17% (4/23) represented contamination from various sources. Specific fingerprints were obtained in 55% (10/18) of the cells from micro-scrape samples. All samples giving sufficient information matched the host DNA fingerprint. All tested blood samples gave specific fingerprints. None of the sampled corneal cells gave a donor DNA fingerprint., Conclusions: In a single patient, no detectable long-term donor cell survival exists at 5 years. Positive identification would have provided unequivocal proof of donor cell survival. This technique gives useful information even if contamination occurs.

Purpose: To demonstrate that the combination of impression cytology and single cell DNA fingerprinting represents a powerful tool that is suitable for detecting transplanted cells after corneal limbal allografting., Methods: Fifty single cells were obtained by corneal impression cytology from 12 patients undergoing cataract surgery. Individual cells were isolated from samples by micromanipulation. Polymerase chain reaction and short tandem repeat profiling was used to obtain forensic standard "DNA fingerprints" from single cells. Blood samples taken at the time of impression cytology provided control "fingerprints.", Results: Informative DNA fingerprints were obtained from all corneal samples and 66% (33 of 50 cells) of isolated single cells. Of all fingerprints obtained, most (91%, 30 of 33 fingerprints) corneal fingerprints matched corresponding blood sample fingerprints. At least one corneal fingerprint matched the corresponding blood sample fingerprint in 83% (10 of 12 patients) of the patients in the study., Conclusions: This extremely specific single cell DNA fingerprinting system permits accurate identification of individual corneal epithelial cells, allowing very reliable determination of their origin, which will enable host and donor cells to be distinguished from each other after keratolimbal allografting procedures, even if the host and donor are the same sex or siblings. These DNA fingerprinting methods allow assessment of quality and quantity of donor cell survival, as well as survival time. The extreme sensitivity and accuracy of the technique means that should contamination occur, it would be identified, thus ensuring meaningful results.

A variety of ligands, including intracellular nucleotides, pharmaceutical products, and neurohormones, influence the adenosine triphosphate (ATP)-sensitive potassium channel of cardiac muscle. In this review it is emphasized that these ligands act not only on the channel-gating mechanism but also influence each others' effects or effectiveness in a quite complex series of interactions. Thus, ATP, which directly closes the channel-gating mechanism, also enhances the efficacy of sulfonylurea drugs and is necessary for the action of certain potassium-channel-opening drugs and neurohormones. Intracellular nucleoside diphosphates that, depending on the conditions, either act on the channel-gating mechanism or influence the effectiveness of ATP, also facilitate and reduce the effectiveness of potassium-channel opening and sulfonylurea drugs, respectively. Our knowledge of the mechanisms that underlie the interactions between these different ligands is limited. The cloning of the channel and the characterization of the different ligand-binding sites will be a great step forward.