Effect of Prognostic Guided Management of Patients With Acute Pulmonary Embolism According to the European Society of Cardiology Risk Stratification Model.

Background: A recent trial showed that management driven by prognostic assessment was effective in reducing the length of stay (LOS) for acute stable pulmonary embolism (PE). The efficacy and safety of this strategy in each subgroup of risk stratification remains unknown. Methods: We conducted a post-hoc analysis of the randomized IPEP study to evaluate the effect of a management strategy guided by early use of a prognostic pathway in the low- and intermediate-high risk subgroups defined by the European Society of Cardiology (ESC) model. These subgroups were retrospectively identified in the control arm. The primary outcome was LOS. The secondary outcomes were 30-day clinical outcomes. Results: Of 249 patients assigned to the intervention group, 60 (24%) were classified as low-, and 30 (12%) as intermediate-high risk. Among 249 patients assigned to the control group, 66 (27%) were low-, and 13 (5%) intermediate-high risk. In the low-risk group, the mean LOS was 2.1 (±0.9) days in the intervention group and 5.3 (±2.9) days in the control group (P < 0.001). In this group, no significant differences were observed in 30-day readmissions (0% vs. 3.0%, respectively), all-cause (0% vs. 0%) and PE-related mortality rates (0% vs. 0%), or severe adverse events (0% vs. 1.5%). In the intermediate-high risk group, the mean LOS was 5.3 (±1.8) days in the intervention group and 6.5 (±2.5) days in the control group (P = 0.08). In this group, no significant differences were observed in 30-day readmissions (3.3% vs. 3.0%, respectively), all-cause (6.7% vs. 7.7%) and PE-related mortality rates (6.7% vs. 7.7%), or severe adverse events (16.7% vs. 15.4%). Conclusion: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE without comprising safety across subgroups of risk stratification. Clinical Trial Registration: [ClinicalTrials.gov], Identifier [NCT02733198].

Acute Dyspnea and Hemoptysis in an 84-Year-Old Man With Multiple Comorbidities.

CASE PRESENTATION: An 84-year-old man with an active smoking habit presented to the ED with dyspnea, hemoptysis, and thick phlegm that was difficult to clear. He reported no weight loss, no fever, and no chest pain or dysphonia. He denied both international travel and previous contact with confirmed cases of TB or SARS-CoV-2. He had no known occupational exposures. The patient's personal history included a resolved complete atrioventricular block that required a permanent pacemaker, moderate-to-severe COPD, rheumatoid arthritis (treated with oral prednisone, 2.5 mg/d) and B-chronic lymphocytic leukemia (treated with methotrexate and prophylactic oral supplements of ferrous sulfate). Moreover, he was in medical follow up because of a peptic ulcer, atrophic gastritis, and colonic diverticulosis. The patient also had a history of thoracic surgery after an episode of acute mediastinitis from an odontogenic infection, which required ICU management and temporal tracheostomy.

Prognostic significance of computed tomography-assessed right ventricular enlargement in low-risk patients with pulmonary embolism: Systematic review and meta-analysis.

BACKGROUND: For patients with acute low-risk pulmonary embolism (PE), determined by a validated clinical prognostic score, the additive prognostic significance of computed tomography (CT)-assessed right ventricular (RV) enlargement is uncertain. METHODS: We performed a systematic review and meta-analysis of studies that enrolled patients with acute low-risk PE to assess the prognostic value of concomitant CT-assessed RV enlargement for 30-day all-cause mortality and PE-related death. We conducted unrestricted searches of PubMed and Embase through December 2019. We used a random-effects model to pool study results; Begg rank correlation method to evaluate for publication bias; and I2 testing to assess for heterogeneity. RESULTS: Of the 7 cohorts with 2197 participants who had low-risk PE and provided results on the primary outcome, 743 (34%; 95% confidence interval [CI], 32-36%) patients had concomitant RV enlargement. Six of 743 (0.8%; 95% CI, 0.3-1.8%) patients with concomitant RV enlargement died 30-days after the diagnosis of PE compared with 3 of 1454 (0.2%, 95% CI, 0-0.6%) without RV enlargement. CT-assessed RV enlargement did not have a significant association with 30-day all-cause mortality (odds ratio [OR], 2.6; 95% CI, 0.7-9.4; I2 = 0%; P = 0.15) or PE-related mortality (OR, 2.8; 95% CI, 0.7-12.1; I2 = 0%; P = 0.16). CONCLUSIONS: CT-assessed RV enlargement occurs in a third of PE patients identified as low-risk by clinical scores. Mortality rate in these patients is low, and CT-assessed RV enlargement was not associated with a significantly increased risk of death within 30 days of PE diagnosis.

Implications of Abnormal Troponin Levels With Normal Right Ventricular Function in Normotensive Patients With Acute Pulmonary Embolism.

Among patients with pulmonary embolism (PE), various permutations of normal or abnormal cardiac troponin results and normal or abnormal echocardiographic right ventricular function are encountered in clinical practice. We aimed to explore whether there is a true gradient of risk based on troponin and echocardiographic results. This study included normotensive patients with PE from the PROgnosTic valuE of CT scan in hemodynamically stable patients with acute symptomatic pulmonary embolism (PROTECT) study. Patients were categorized as having -Troponin/-Echo, -Troponin/+Echo, +Troponin/-Echo, and +Troponin/+Echo. The primary outcome was 30-day "complicated course," including death from any cause, hemodynamic collapse, or recurrent PE. Secondary outcomes included individual adverse event rates. Of the 834 patients who had echocardiographic and troponin results, 569 patients (68%) had -Troponin/-Echo, 126 patients (15%) had -Troponin/+Echo, 74 patients (8.9%) had +Troponin/-Echo, and 65 patients (7.8%) had +Troponin/+Echo. The incidence of 30-day complicated course was 4.6% in patients with -Troponin/-Echo, 11.9% in patients with -Troponin/+Echo, 13.5% in patients with +Troponin/-Echo, and 16.9% in patients with +Troponin/+Echo (P for trend <0.001). In the subgroup of patients with a high-risk sPESI (i.e., intermediate-risk according to the ESC guidelines) (n = 527), the incidence of 30-day complicated course was 14.9% in patients with -Troponin/+Echo, 18.5% in patients with +Troponin/-Echo, and 17.5% in patients with +Troponin/+Echo (P for trend <0.01). In patiens with PE, there seems to be a risk gradient based on troponin and echocardiographic results. This study did not detect a significant risk difference in those with +Troponin/-Echo compared with -Troponin/+Echo.

The 4 U's Rule of Fibromyalgia: A Proposed Model for Fatigue in a Sample of Women with Fibromyalgia: A Qualitative Study.

Although fatigue usually goes unnoticed, it is a symptom that poses great challenges to patients with fibromyalgia and is a strong limitation. The aim of this study is to identify and describe the variables involved in fatigue in nine different situations of the Goal Pursuit Questionnaire (GPQ) that may occur in the daily lives of women with fibromyalgia, according to an ABC (Antecedents-Behaviors-Consequences) model. This study followed a qualitative descriptive research method and a deductive-inductive hybrid approach based on a phenomenological paradigm. Twenty-six women with fibromyalgia participated in focus group discussions between February and March of 2018. Thematic content analysis was carried out from transcribed verbatim interviews. We identified nine major themes that emerged from the participants' conversations: self-imposed duties, muscle fatigue, overwhelming feeling of tiredness, difficulty thinking, difficulty concentrating, negative emotions, lifestyle changes, affected everyday activities, and lack of motivation for daily activities and social interactions. We conclude that the ABC model allowed certain elements to emerge regarding the fatigue experience, highlighting its importance as a symptom in fibromyalgia. This additional analysis of the ABC model showed that fatigue can be described through the 4 U's Rule, which is integrated by these four adjectives: (1) Unpredictable, (2) Uncontrollable, (3) Unseen, and (4) Unintelligible. Identifying these characteristics can contribute to a better understanding of fibromyalgia in addition to better treatment for these patients.

Need for Transthoracic Echocardiogram in Patients with Low-Risk Pulmonary Thromboembolism: A Systematic Review and Meta-Analysis. / Necesidad de una ecocardiografía transtorácica en pacientes con tromboembolia de pulmón de riesgo bajo: revisión sistemática y metanálisis.

INTRODUCTION: It is unclear whether low-risk patients with acute symptomatic pulmonary embolism (PE) should undergo echocardiogram. METHODS: We performed a meta-analysis of studies that enrolled patients with acute low-risk PE to assess the prognostic value of echocardiographic diagnosis of right ventricular (RV) dysfunction for the primary outcome of short-term all-cause mortality, and the secondary outcome of short-term PE-related mortality. We used a random-effects model to pool study results, a Begg rank correlation method to evaluate for publication bias, and I2 testing to assess heterogeneity. RESULTS: The meta-analysis included a total of 11 studies 1,868 patients with low-risk PE. Ten of the 447 (2.2%; 1.1%-4.1%) low-risk patients with echocardiographic RV dysfunction died soon after the diagnosis of PE compared with 10 of 1,421 (0.7%; 0.3-1.3%) patients without RV dysfunction. RV dysfunction was not significantly associated with short-term all-cause mortality (odds ratio 2.0; 95% confidence interval, 0.8-5.1, p=.14; I2=8%). RV dysfunction was significantly associated with short-term PE-related mortality (odds ratio 5.2; 95% confidence interval, 1.7-16, p <.01; I2=0%). CONCLUSIONS: In patients with low-risk PE, echocardiographic RV dysfunction is not associated with all-cause mortality, but identifies patients with an increased risk for short-term PE-related mortality.

CRISPR/Cas9-targeted enrichment and long-read sequencing of the Fuchs endothelial corneal dystrophy-associated TCF4 triplet repeat.

PURPOSE: To demonstrate the utility of an amplification-free long-read sequencing method to characterize the Fuchs endothelial corneal dystrophy (FECD)-associated intronic TCF4 triplet repeat (CTG18.1). METHODS: We applied an amplification-free method, utilizing the CRISPR/Cas9 system, in combination with PacBio single-molecule real-time (SMRT) long-read sequencing, to study CTG18.1. FECD patient samples displaying a diverse range of CTG18.1 allele lengths and zygosity status (n = 11) were analyzed. A robust data analysis pipeline was developed to effectively filter, align, and interrogate CTG18.1-specific reads. All results were compared with conventional polymerase chain reaction (PCR)-based fragment analysis. RESULTS: CRISPR-guided SMRT sequencing of CTG18.1 provided accurate genotyping information for all samples and phasing was possible for 18/22 alleles sequenced. Repeat length instability was observed for all expanded (≥50 repeats) phased CTG18.1 alleles analyzed. Furthermore, higher levels of repeat instability were associated with increased CTG18.1 allele length (mode length ≥91 repeats) indicating that expanded alleles behave dynamically. CONCLUSION: CRISPR-guided SMRT sequencing of CTG18.1 has revealed novel insights into CTG18.1 length instability. Furthermore, this study provides a framework to improve the molecular diagnostic accuracy for CTG18.1-mediated FECD, which we anticipate will become increasingly important as gene-directed therapies are developed for this common age-related and sight threatening disease.

Antisense Therapy for a Common Corneal Dystrophy Ameliorates TCF4 Repeat Expansion-Mediated Toxicity.

Fuchs endothelial corneal dystrophy (FECD) is a common disease for which corneal transplantation is the only treatment option in advanced stages, and alternative treatment strategies are urgently required. Expansion (≥50 copies) of a non-coding trinucleotide repeat in TCF4 confers >76-fold risk for FECD in our large cohort of affected individuals. An FECD subject-derived corneal endothelial cell (CEC) model was developed to probe disease mechanism and investigate therapeutic approaches. The CEC model demonstrated that the repeat expansion leads to nuclear RNA foci, with the sequestration of splicing factor proteins (MBNL1 and MBNL2) to the foci and altered mRNA processing. Antisense oligonucleotide (ASO) treatment led to a significant reduction in the incidence of nuclear foci, MBNL1 recruitment to the foci, and downstream aberrant splicing events, suggesting functional rescue. This proof-of-concept study highlights the potential of a targeted ASO therapy to treat the accessible and tractable corneal tissue affected by this repeat expansion-mediated disease.