Chronic thromboembolic pulmonary hypertension

C hronic thromboembolic pulmonary hypertension is defined as mean pulmonary-artery pressure greater than 25 mm Hg that persists 6 months after pulmonary embolism is diagnosed. The 2008 World Symposium on Pulmonary Hypertension 1 emphasized the importance of chronic thromboembolic pulmonary hypertension, which occurs in 2 to 4% of patients after acute pulmonary embolism. 2,3 The frequency of this condition among patients with pulmonary hypertension is unknown. Patients with chronic thromboembolic pulmonary hypertension generally present in their 40s, although this condition has been reported in patients in other age groups. 2 The diagnosis is often overlooked because many patients do not have a history of clinically overt pulmonary embolism. Although symptomatic disease develops in a substantial proportion of patients, the clinical importance of asymptomatic chronic thromboembolic pulmonary hypertension remains controversial. This condition is usually detected when pulmonary hypertension worsens and causes dyspnea, hypoxemia, and right ventricular dysfunction. Death is usually due to progressive pulmonary hypertension culminating in right ventricular failure. The risk of the development of chronic thromboembolic pulmonary hypertension is increased by factors associated with pulmonary embolism, certain chronic medical conditions, thrombophilia, and a genetic predisposition The New England Journal of Medicine Downloaded from nejm.org at HOSPITAL SIRIO LIBANES on February 1, 2011. For personal use only. No other uses without permission

Adding Stiffness to the Foot Modulates Soleus Force-Velocity Behaviour during Human Walking

Previous studies of human locomotion indicate that foot and ankle structures can interact in complex ways. The structure of the foot defines the input and output lever arms that influences the force-generating capacity of the ankle plantar flexors during push-off. At the same time, deformation of the foot may dissipate some of the mechanical energy generated by the plantar flexors during push-off. We investigated this foot-ankle interplay during walking by adding stiffness to the foot through shoes and insoles, and characterized the resulting changes in in vivo soleus muscle-tendon mechanics using ultrasonography. Added stiffness decreased energy dissipation at the foot (p < 0.001) and increased the gear ratio (i.e., ratio of ground reaction force and plantar flexor muscle lever arms) (p < 0.001). Added foot stiffness also altered soleus muscle behaviour, leading to greater peak force (p < 0.001) and reduced fascicle shortening speed (p < 0.001). Despite this shift in force-velocity behaviour, the whole-body metabolic cost during walking increased with added foot stiffness (p < 0.001). This increased metabolic cost is likely due to the added force demand on the plantar flexors, as walking on a more rigid foot/shoe surface compromises the plantar flexors’ mechanical advantage

Adding Stiffness to the Foot Modulates Soleus Force-Velocity Behaviour during Human Walking

Previous studies of human locomotion indicate that foot and ankle structures can interact in complex ways. The structure of the foot defines the input and output lever arms that influences the force-generating capacity of the ankle plantar flexors during push-off. At the same time, deformation of the foot may dissipate some of the mechanical energy generated by the plantar flexors during push-off. We investigated this foot-ankle interplay during walking by adding stiffness to the foot through shoes and insoles, and characterized the resulting changes in in vivo soleus muscle-tendon mechanics using ultrasonography. Added stiffness decreased energy dissipation at the foot (p \u3c 0.001) and increased the gear ratio (i.e., ratio of ground reaction force and plantar flexor muscle lever arms) (p \u3c 0.001). Added foot stiffness also altered soleus muscle behaviour, leading to greater peak force (p \u3c 0.001) and reduced fascicle shortening speed (p \u3c 0.001). Despite this shift in force-velocity behaviour, the whole-body metabolic cost during walking increased with added foot stiffness (p \u3c 0.001). This increased metabolic cost is likely due to the added force demand on the plantar flexors, as walking on a more rigid foot/shoe surface compromises the plantar flexors’ mechanical advantage

Effects of an Unusual Poison Identify a Lifespan Role for Topoisomerase 2 in Saccharomyces Cerevisiae

A progressive loss of genome maintenance has been implicated as both a cause and consequence of aging. Here we present evidence supporting the hypothesis that an age-associated decay in genome maintenance promotes aging in Saccharomyces cerevisiae (yeast) due to an inability to sense or repair DNA damage by topoisomerase 2 (yTop2). We describe the characterization of LS1, identified in a high throughput screen for small molecules that shorten the replicative lifespan of yeast. LS1 accelerates aging without affecting proliferative growth or viability. Genetic and biochemical criteria reveal LS1 to be a weak Top2 poison. Top2 poisons induce the accumulation of covalent Top2-linked DNA double strand breaks that, if left unrepaired, lead to genome instability and death. LS1 is toxic to cells deficient in homologous recombination, suggesting that the damage it induces is normally mitigated by genome maintenance systems. The essential roles of yTop2 in proliferating cells may come with a fitness trade-off in older cells that are less able to sense or repair yTop2-mediated DNA damage. Consistent with this idea, cells live longer when yTop2 expression levels are reduced. These results identify intrinsic yTop2-mediated DNA damage as a potentially manageable cause of aging

Extended Anticoagulation After Pulmonary Embolism:A Multicenter Observational Cohort Analysis

BACKGROUND: Pulmonary embolism (PE) has a long‐term risk of adverse events, which can be prevented by extended anticoagulation. We compared clinical characteristics and outcomes between patients treated with 2‐year extended anticoagulation and those who were not, in a population who had completed an initial phase of 3 to 6 months of anticoagulant therapy after acute PE. METHODS AND RESULTS: Observational cohort analysis of patients with PE who survived an initial phase of 3 to 6 months anticoagulation. Primary efficacy outcome was all‐cause death or recurrent venous thromboembolism. Primary safety outcome was major bleeding. In total, 858 (71.5%) patients were treated with and 341 (28.5%) were treated without extended anticoagulant therapy during the active study period. Age <65 years, intermediate‐high or high‐risk index PE, normal platelet count, and the absence of concomitant antiplatelet treatment were independently associated with the prescription of extended anticoagulation. The mean duration of the active phase was 2.1±0.3 years. The adjusted rate of the primary efficacy outcome was 2.1% in the extended group and 7.7% in the nonextended group (P<0.001) for patients treated with extended anticoagulant therapy. Rate of bleeding were similar between the extended anticoagulant group and the nonextended group. CONCLUSIONS: Extended oral anticoagulation over 2 and a half years after index PE seems to provide a net clinical benefit compared with no anticoagulation in patients with PE selected to receive extended anticoagulation. Randomized clinical trials are warranted to explore the potential benefit of extended anticoagulation in patients with PE, especially those with transient provoking factors but residual risk

Social determinants of health in pulmonary embolism management and outcome in hospitals: Insights from the United States nationwide inpatient sample

BACKGROUND The role of social determinants in the treatment and course of acute pulmonary embolism (PE) is understudied. OBJECTIVE To investigate the association between social determinants of health with in-hospital management and early clinical outcomes following acute PE. METHODS We identified hospitalizations of adults with acute PE discharge diagnosis from the nationwide inpatient sample (2016-2018). Multivariable regression was used to investigate the association between race/ethnicity, type of expected primary payer, and income with the use of advanced PE therapies (thrombolysis, catheter-directed treatment, surgical embolectomy, extracorporeal membrane oxygenation), length of stay, hospitalization charges, and in-hospital death. RESULTS A total of 1,124,204 hospitalizations with a PE diagnosis were estimated from the 2016-2018 nationwide inpatient sample, corresponding to a hospitalization rate of 14.9/10,000 adult persons-year. The use of advanced therapies was lower in Black and Asian/Pacific Islander (vs. White patients: adjusted odds ratio [OR$_{adjusted}$], 0.87; 95% confidence interval [CI], 0.81-0.92 and OR$_{adjusted}$ 0.76; 95% CI, 0.59-0.98) and in Medicare- or Medicaid-insured (vs. privately-insured; OR$_{adjusted}$, 0.73; 95% CI, 0.69-0.77 and OR$_{adjusted}$, 0.68; 95% CI, 0.63-0.74), although they had the greatest length of stay and hospitalization charges. In-hospital mortality was higher in the lowest income quartile (vs. highest quartile; OR$_{adjusted}$, 1.09; 95% CI, 1.02-1.17). Among high-risk PE, patients of other than the White race had the highest in-hospital mortality. CONCLUSION We observed inequalities in advanced therapies used for acute PE and higher in-hospital mortality in races other than White. Low socioeconomic status was also associated with lesser use of advanced treatment modalities and greater in-hospital mortality. Future studies should further explore and consider the long-term impact of social inequities in PE management

Risk of Recurrent Venous Thromboembolism in Selected Subgroups of Men:A Danish Nationwide Cohort Study

Background  Although men are considered at high risk for recurrent venous thromboembolism (VTE), sex-specific data on prognostic factors are lacking. We estimated the cumulative recurrence risks associated with clinical characteristics and comorbidities known or suspected to be associated with the development of VTE recurrence: major surgery, trauma, history of cancer, rheumatic disorder, ischemic heart disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes, chronic renal disease, varicose veins, alcohol-related diseases, and arterial hypertension. Methods  We linked nationwide Danish health registries to identify all incident VTE in- and outpatients in men from 2008 through 2018. Recurrent VTE risk 2 years after anticoagulant discontinuation was calculated using the Aalen-Johansen estimator, stratified by age above/below 50 years. Results  The study included 13,932 men with VTE, of whom 21% ( n  = 2,898) were aged <50 years. For men aged <50 years with at least one of the clinical characteristics, 2-year recurrence risk ranged from 6% (major surgery) to 16% (history of cancer). For men ≥50 years with at least one of the characteristics, recurrence risk ranged from 7% (major surgery) to 12% (ischemic heart disease, chronic obstructive pulmonary disease, and chronic renal disease). Men aged <50 and ≥50 years without the clinical characteristics all had a recurrence risk of 10%. Discussion  We demonstrated a 2-year recurrence risk of at least 6%, regardless of age category and disease status, in this nationwide cohort of men with VTE. The recurrence risk must be balanced against bleeding risk. However, the high recurrence risk across all subgroups might ultimately lead to greater emphasis on male sex in future guidelines focusing on optimized secondary VTE prevention

The Risk Assessment and Prediction Tool (RAPT) for Discharge Planning in a Posterior Lumbar Fusion Population

BACKGROUND: As the use of bundled care payment models has become widespread in neurosurgery, there is a distinct need for improved preoperative predictive tools to identify patients who will not benefit from prolonged hospitalization, thus facilitating earlier discharge to rehabilitation or nursing facilities.OBJECTIVE: To validate the use of Risk Assessment and Prediction Tool (RAPT) in patients undergoing posterior lumbar fusion for predicting discharge disposition.METHODS: Patients undergoing elective posterior lumbar fusion from June 2016 to February 2017 were prospectively enrolled. RAPT scores and discharge outcomes were recorded for patients aged 50 yr or more (n = 432). Logistic regression analysis was used to assess the ability of RAPT score to predict discharge disposition. Multivariate regression was performed in a backwards stepwise logistic fashion to create a binomial model.RESULTS: Escalating RAPT score predicts disposition to home (P \u3c .0001). Every unit increase in RAPT score increases the chance of home disposition by 55.8% and 38.6% than rehab and skilled nursing facility, respectively. Further, RAPT score was significant in predicting length of stay (P = .0239), total surgical cost (P = .0007), and 30-d readmission (P \u3c .0001). Amongst RAPT score subcomponents, walk, gait, and postoperative care availability were all predictive of disposition location (P \u3c .0001) for both models. In a generalized multiple logistic regression model, the 3 top predictive factors for disposition were the RAPT score, length of stay, and age (P \u3c .0001, P \u3c .0001 and P = .0001, respectively).CONCLUSION: Preoperative RAPT score is a highly predictive tool in lumbar fusion patients for discharge disposition

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Atrial fibrillation; Mortality; Pulmonary embolismFibrilación auricular; Mortalidad; Embolia pulmonarFibril·lació auricular; Mortalitat; Embòlia pulmonarBackground Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90‐day and 1‐year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90‐day all‐cause (odds ratio [OR], 2.81; 95% CI, 2.33–3.38) and PE‐related mortality (OR, 2.38; 95% CI, 1.37–4.14) and increased 1‐year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10–9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all‐cause mortality (OR, 1.91; 95% CI, 1.57–2.32) but not PE‐related mortality (OR, 1.50; 95% CI, 0.85–2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90‐day all‐cause (OR, 2.28; 95% CI, 1.75–2.97) and PE‐related (OR, 3.64; 95% CI, 2.01–6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.None