Evaluating atrial fibrillation artificial intelligence for the ED: statistical and clinical implications.

OBJECTIVE: An artificial intelligence (AI) algorithm has been developed to detect the electrocardiographic signature of atrial fibrillation (AF) present on an electrocardiogram (ECG) obtained during normal sinus rhythm. We evaluated the ability of this algorithm to predict incident AF in an emergency department (ED) cohort of patients presenting with palpitations without concurrent AF. METHODS: This retrospective study included patients 18 years and older who presented with palpitations to one of 15 ED sites and had a 12­lead ECG performed. Patients with prior AF or newly diagnosed AF during the ED visit were excluded. Of the remaining patients, those with a follow up ECG or Holter monitor in the subsequent year were included. We evaluated the performance of the AI-ECG output to predict incident AF within one year of the index ECG by estimating an area under the receiver operating characteristics curve (AUC). Sensitivity, specificity, and positive and negative predictive values were determined at the optimum threshold (maximizing sensitivity and specificity), and thresholds by output decile for the sample. RESULTS: A total of 1403 patients were included. Forty-three (3.1%) patients were diagnosed with new AF during the following year. The AI-ECG algorithm predicted AF with an AUC of 0.74 (95% CI 0.68-0.80), and an optimum threshold with sensitivity 79.1% (95% Confidence Interval (CI) 66.9%-91.2%), and specificity 66.1% (95% CI 63.6%-68.6%). CONCLUSIONS: We found this AI-ECG AF algorithm to maintain statistical significance in predicting incident AF, with clinical utility for screening purposes limited in this ED population with a low incidence of AF.

A Delayed Case of Pericarditis Following Recovery From COVID-19 Infection.

Pericarditis is a rare cardiac complication of coronavirus 19 (COVID-19) infection. Recent case reports describe severe sequelae of pericarditis, including cardiac tamponade, developing within days of initial COVID-19 symptoms. We present a case of pericarditis with slower onset and milder symptoms, developing over a period of a few weeks in an immunocompetent male who recovered from COVID-19 several months earlier. A 65-year-old male presented to an emergency department several times for one week of worsening chest and neck symptoms, along with fever. He had been symptom-free after a three-day course of cough, myalgias, and fever with positive COVID-19 testing, approximately 70 days earlier. He was ultimately admitted for fever and pericarditis with an associated pericardial effusion and positive PCR testing for COVID-19. Pericarditis should be considered in the differential diagnosis for patients with COVID-19 and unexplained persistent chest symptoms. The possibility of recurrent or atypical latent infection should additionally be considered in the months following the initial COVID-19 infection. Bedside ultrasound may facilitate early diagnosis and management of COVID-19 associated pericarditis.

A Case of COVID-19 Re-Infection in a Liver Transplant Patient.

Coronavirus disease 2019 (COVID-19) is an ongoing worldwide pandemic infection. The exact incidence of disease re-infection or recurrence remains unknown. One particular at-risk population includes individuals with solid organ transplantation on immunosuppression. We present a case of COVID-19 re-infection in a chronically immunocompromised liver transplant patient. A 53-year-old female presented to the Emergency Department (ED) with nausea, vomiting, diarrhea, and myalgias. She was found to test positive for COVID-19. Her relevant medical history included liver transplantation on chronic immunosuppression. More recently, she had tested positive for COVID-19 approximately three months prior to this and was hospitalized at that time for encephalopathy and treated with remdesivir and convalescent plasma. She had subsequently recovered with negative COVID-19 testing in the interim. On the ED presentation with presumed re-infection, her disease was deemed to be mild with lack of severe symptoms or pulmonary involvement, and she was discharged with outpatient follow-up for monoclonal antibody infusion therapy. We describe a scenario of presumed COVID-19 re-infection in a liver transplant patient. To our knowledge, this is a rare event and has been reported internationally in only a handful of individuals. We surmise that immunosuppression could offer some protection from the inflammatory cascade of the initial disease process in COVID-19 given the relatively mild disease observed in our patient. On the other hand, a less robust immune response may decrease humoral immunity and leave patients at greater risk of re-infection. Further investigation is necessary to delineate COVID-19 disease re-infection versus relapse, especially in the setting of an immunocompromised state.

Differences Between Esophageal and Tracheal Intubation Ultrasound View Proficiency: An Educational Study of Novice Prehospital Providers.

Objectives Airway ultrasound is now possible in the prehospital setting due to advances in ultrasound equipment portability. We questioned how well prehospital providers without prior experience could determine both esophageal and tracheal placement of an endotracheal tube in cadavers after a brief training course in ultrasound.  Methods This educational prospective study at the Simulation Center in Mayo Clinic Jacksonville Florida enrolled 50 prehospital providers. Demographic and practice background information was obtained through surveys. Each participant performed a baseline ultrasound to determine endotracheal tube placement in a cadaver that was randomly assigned to an esophageal or tracheal intubation. Participants then repeated the randomized testing after a 15-minute tutorial. Before and after overall accuracy as well as proportions of correct identification of esophageal and tracheal intubations were determined and compared using standard binomial proportion and McNemar's tests. Results  None of the participants had prior experience of performing airway ultrasound. Baseline group scores were 60% (CI 45%-74%) for overall accuracy (n=50), 55% (CI 32%-76%) for correct identification of an esophageal intubation, and 64% (CI 44%-81%) for correct tracheal detection. Baseline scores were not significantly different from standard binomial distributions. Post-test scores were 82% (CI 69%-91%) for overall accuracy, 96% (CI 80%-100%) for esophageal intubation detection, and 66.7% (CI 45%-84%) for tracheal intubation detection, with corresponding binomial p-values of <0.001, <0.001, and 0.15. P-values for McNemar's paired test for combined overall accuracy, correct esophageal detection, and correct tracheal detection were 0.04, 0.02, and 0.62, respectively. Conclusions Prehospital participants without prior ultrasound experience demonstrated significant gains in airway ultrasound proficiency after a limited introductory course. Post-training score increases were largely due to a notable increase in correct esophageal intubation detection rates. Learners did not make significant progress in correctly identifying a tracheal intubation. Airway ultrasound educational design may benefit from added emphasis on the potentially more difficult to recognize tracheal intubation view.

Mechanism of initiation site selection promoted by the human rhinovirus 2 internal ribosome entry site.

Translation initiation site usage on the human rhinovirus 2 internal ribosome entry site (IRES) has been examined in a mixed reticulocyte lysate/HeLa cell extract system. There are two relevant AUG triplets, both in a base-paired hairpin structure (domain VI), with one on the 5' side at nucleotide (nt) 576, base paired with the other at nt 611, which is the initiation site for polyprotein synthesis. A single residue was inserted in the apical loop to put AUG-576 in frame with AUG-611, and in addition another in-frame AUG was introduced at nt 593. When most of the IRES was deleted to generate a monocistronic mRNA, the use of these AUGs conformed to the scanning ribosome model: improving the AUG-576 context increased initiation at this site and decreased initiation at downstream sites, whereas the converse was seen when AUG-576 was mutated to GUA; and AUG-593, when present, took complete precedence over AUG-611. Under IRES-dependent conditions, by contrast, much less initiation occurred at AUG-576 than in a monocistronic mRNA with the same AUG-576 context, mutation of AUG-576 decreased initiation at downstream sites by approximately 70%, and introduction of AUG-593 did not completely abrogate initiation at AUG-611, unless the apical base pairing in domain VI was destroyed by point mutations. These results indicate that ribosomes first bind at the AUG-576 site, but instead of initiating there, most of them are transferred to AUG-611, the majority by strictly linear scanning and a substantial minority by direct transfer, which is possibly facilitated by the occasional persistence of base pairing in the apical part of the domain VI stem.

The mechanism of an exceptional case of reinitiation after translation of a long ORF reveals why such events do not generally occur in mammalian mRNA translation.

The subgenomic mRNA of feline caliciviruses is bicistronic with the two cistrons overlapping by four nucleotides, ..AUGA. The upstream cistron encodes a 75-kDa major capsid protein precursor (pre-VP1), and the downstream cistron a 10-kDa minor capsid protein. The kinetics of translation in reticulocyte lysates show that the downstream cistron is translated by a termination-reinitiation process, which is unusual in not requiring eIF4G or the eIF4F complex. Reinitiation requires the 3'-terminal 87 nucleotides (nt) of the pre-VP1 ORF, but no other viral sequences. The reinitiation site is selected by virtue of its proximity to this 87-nt element, and not its proximity to the pre-VP1 ORF stop codon, although this must be located not more than approximately 30 nt downstream from the restart codon. This 87-nt element was shown to bind 40S ribosomal subunits and initiation factor eIF3, and addition of supplementary eIF3 enhanced reinitiation efficiency. Mutants defective in reinitiation showed reduced affinity for eIF3 or defective 40S subunit binding (or both). These results suggest a mechanism in which some of the eIF3/40S complexes formed during disassembly of post-termination ribosomes bind to this 87-nt element in a position appropriate for reinitiation following acquisition of an eIF2/GTP/Met-tRNA i ternary complex.

What determines whether mammalian ribosomes resume scanning after translation of a short upstream open reading frame?

If the 5'-proximal AUG triplet in a mammalian mRNA is followed by a short open reading frame (sORF), a significant fraction of ribosomes resume scanning after termination of sORF translation, and reinitiate at a downstream AUG. To examine the underlying mechanism, we examined reinitiation in vitro using a series of mRNAs that differed only in the 5'-untranslated region (UTR). Efficient reinitiation was found to occur only if the eIF4F complex, or at a minimum the central one-third fragment of eIF4G, participated in the primary initiation event at the sORF initiation codon. It did not occur, however, when sORF translation was driven by the classical swine fever virus or cricket paralysis virus internal ribosome entry sites (IRESs), which do not use eIF4A, 4B, 4E, or 4G. A critical test was provided by an mRNA with an unstructured 5'-UTR, which is translated by scanning but does not absolutely need eIF4G and eIF4A: There was efficient reinitiation in a standard reticulocyte lysate, when initiation would be largely driven by eIF4F, but no reinitiation in an eIF4G-depleted lysate. These results suggest that resumption of scanning may depend on the interaction between eIF4F (or the eIF4G central domain) and the ribosome being maintained while the ribosome translates the sORF.

Cardiorespiratory effects of added dead space in patients with heart failure and central sleep apnea.

BACKGROUND: Inhaled CO(2) has been shown to stabilize the breathing pattern of patients with central sleep apnea (CSA) with and without congestive heart failure (CHF). Added dead space (DS) as a form of supplemental CO(2) was effective in eliminating idiopathic CSA. The efficacy and safety of DS has not yet been evaluated in patients with CHF and CSA. METHODS: We examined the respiratory and cardiovascular effects of added DS in eight patients with CHF and CSA. The DS consisted of a facemask attached to a cylinder of adjustable volume. During wakefulness, the cardiorespiratory response to 200 to 600 mL of DS was tested. Cardiac output and stroke volume were measured using echocardiography with and without DS. During the nocturnal study, patients slept with and without DS, alternating at approximately 1-h intervals. RESULTS: Values are expressed as the mean +/- SE. The wakefulness study revealed a plateau in the partial pressure of end-tidal CO(2) (PETCO(2)) and the partial pressure of end-tidal O(2) between DS amounts of 400 and 600 mL. The mean stroke volume index (33 +/- 7 vs 34 +/- 7 mL/m(2), respectively) and the mean cardiac index (1.9 +/- 0.3 vs 1.9 +/- 0.4 L/min/m(2), respectively) were not affected by DS. Neither heart rate nor BP showed a significant change in response to DS of < or = 600 mL. During sleep, DS increased the PETCO(2) (40.7 +/- 2.7 vs 38.9 +/- 2.6 mm Hg, respectively; p < 0.05), reduced apnea (1 +/- 1 vs 29 +/- 7 episodes per hour, respectively; p < 0.01) and arousal (21 +/- 8 vs 30 +/- 8 arousals per hour, respectively; p < 0.05), increased the mean arterial oxygen saturation (SaO(2)) [94.4 +/- 1.0% vs 93.5 +/- 1.1%, respectively; p < 0.01), and reduced SaO(2) oscillations (DeltaSaO(2) from maximum to minimum, 1.8 +/- 0.4% vs 5.5 +/- 0.9%, respectively; p < 0.01). CONCLUSION: DS stabilized CSA and improved sleep quality in patients with CHF without significant acute adverse effects on the cardiovascular function.

The influence of viral coding sequences on pestivirus IRES activity reveals further parallels with translation initiation in prokaryotes.

Classical swine fever virus (CSFV) is a member of the pestivirus family, which shares many features in common with hepatitis C virus (HCV). It is shown here that CSFV has an exceptionally efficient cis-acting internal ribosome entry segment (IRES), which, like that of HCV, is strongly influenced by the sequences immediately downstream of the initiation codon, and is optimal with viral coding sequences in this position. Constructs that retained 17 or more codons of viral coding sequence exhibited full IRES activity, but with only 12 codons, activity was approximately 66% of maximum in vitro (though close to maximum in transfected BHK cells), whereas with just 3 codons or fewer, the activity was only approximately 15% of maximum. The minimal coding region elements required for high activity were exchanged between HCV and CSFV. Although maximum activity was observed in each case with the homologous combination of coding region and 5' UTR, the heterologous combinations were sufficiently active to rule out a highly specific functional interplay between the 5' UTR and coding sequences. On the other hand, inversion of the coding sequences resulted in low IRES activity, particularly with the HCV coding sequences. RNA structure probing showed that the efficiency of internal initiation of these chimeric constructs correlated most closely with the degree of single-strandedness of the region around and immediately downstream of the initiation codon. The low activity IRESs could not be rescued by addition of supplementary eIF4A (the initiation factor with ATP-dependent RNA helicase activity). The extreme sensitivity to secondary structure around the initiation codon is likely to be due to the fact that the eIF4F complex (which has eIF4A as one of its subunits) is not required for and does not participate in initiation on these IRESs.