Surface engineering of metal-organic framework nanoparticles-based miRNA carrier: Boosting RNA stability, intracellular delivery and synergistic therapy.

MicroRNAs (miRNAs) are small noncoding RNAs that are critical for the regulation of multiple physiological and pathological processes, thus holding great clinical potential. However, the therapeutic applications of miRNAs are severely limited by their biological instability and poor intracellular delivery. Herein, we describe a dual-layers surface engineering strategy to design an efficient miRNA delivery nanosystem based on metal-organic frameworks (MOFs) incorporating lipid coating. The resulting nanoparticle system was demonstrated to protect miRNA from ribonuclease degradation, enhance cellular uptake and facilitate lysosomal escape. These ensured effective miRNA mediated gene therapy, which synergized with MOF-specific photodynamic therapy and pre-encapsulated doxorubicin (Dox) chemotherapy to provide a multifunctional with therapeutic effectiveness against cencer cells The mechanisms of miRNA binding and Dox loading were revealed, demonstrating the potential of the present MOFs surface-engineered strategy to overcome their inherent pore-size restriction for macromolecular miRNA carrying, enableefficient co-delivery. In vitro studies revealed the potential of our multifunctional system for miRNA delivery and the demonstrated the therapeutic effectiveness against cancer cells, thereby providing a versatile all-in-one MOFs strategy for delivery of nucleic acids and diverse therapeutic molecules in synergistic therapy.

Impact of an emergency department nurse training intervention on the adequacy of thromboprophylaxis for venous thromboembolism: the PROTESU III study. / Impacto de una intervención formativa en enfermería de urgencias sobre la adecuación de la profilaxis de la enfermedad tromboembólica venosa: estudio PROTESU III.

OBJECTIVE: Objectives. To assess the impact of training for emergency department (ED) nurses on adequate thromboprophylaxis for patients admitted to hospital from the ED for medical conditions. Methods. Multicenter quasiexperimental pre-post study of an ED nurse training intervention in 8 hospitals. Patients were recruited from January 2022 through May 2023 in 3 phases: before nurse training, in the first month after training, and in the sixth month after training. Included were patients attended in the ED for medical conditions. Adequate thromboprophylaxis was defined as 1) use of prophylactic drugs in patients at high risk for venousthromboembolism according to the Padua Prediction Score (PPS), and 2) nonuse in patients at low risk. We compared the percentage of adequate prophylaxis in the first phase to the percentages in the second and third phases. Results. A total of 928 patients were included (326 in phase 1, 295 in phase 2, and 307 in phase 3). PPS scores indicated that 238 (73%) of the patients were at high risk in phase 1 vs 189 (64.1%, P = .016) in phase 2 and 207 (67.4%, P = .125) in phase 3. A total of 187 patients (57.4%, 95% CI, 51.8%-62.8%) were adequatelythromboprophylaxed in phase 1 vs 178 (60.%, 95% CI, 54.5%-66%) in phase 2 (absolute difference in proportions, 3.0% (95% CI, -4.8% to 10.6%; P = .462)]. In phase 3, 166 patients (54.1%, 95% CI, 48.3%-59.7%) received adequate prophylaxis (difference, -3.3% (95% CI, -11.0% to 4.4%; P = .405). Conclusions. A training intervention for ED nurses, implemented as an isolated strategy, had no impact on the adequacy of thromboprophylaxis in patients admitted from the ED for medical conditions.

OBJETIVO: Objetivos. Evaluar el impacto de una intervención formativa en enfermería de urgencias sobre la adecuación de la tromboprofilaxis farmacológica de los pacientes ingresados por patología médica. Método. Estudio cuasiexperimental, multicéntrico (8 hospitales), pre y posintervención, con 3 fases de reclutamiento (enero 2022-mayo 2023): primera,preintervención; segunda, en el primer mes tras la intervención; y tercera, al sexto mes. Se incluyeron los pacientes atendidos en urgencias que requirieron ingreso por enfermedad médica. La adecuación de la tromboprofilaxis farmacológica se definió como: 1) la utilización en pacientes clasificados en el grupo de riesgo alto por la Escala de Padua (PPS); o 2) la no utilización en pacientes clasificados de riesgo bajo. Se compararon los porcentajes de adecuación de las fases 2 y 3 frente a la fase 1. Resultados. Se incluyeron 928 pacientes: 326 en la fase 1; 295 en la fase 2; y 307 en la fase 3. En la fase 1, 238 pacientes (73%) fueron clasificados de riesgo alto por PPS; en la fase 2, 189 (64,1%) (p = 0,016); y en la fase 3, 207 (67,4%) (p = 0,125). La tromboprofilaxis farmacológica fue adecuada en 187 pacientes (57,4%, IC 95% 51,8-62,8%) de la fase 1; en 178 (60,3%, IC 95% 54,5 66%) de la fase 2 [diferencia absoluta proporciones (DAP) 3,0% (IC 95% de ­4,8 a +10,6%), p = 0,462], y en 166 (54,1%, IC 95% 48,3-59,7%) de la fase 3 [DAP 3,3% (IC 95% de ­11,0 a +4,4%, p = 0,405]. Conclusiones. Una intervención formativa aislada en la enfermería de urgencias no tuvo impacto sobre la adecuación de la tromboprofilaxis farmacológica en urgencias de los pacientes que ingresan por enfermedad médica.

International Clinical Practice Guideline Recommendations for Acute Pulmonary Embolism: Harmony, Dissonance, and Silence.

Despite abundant clinical innovation and burgeoning scientific investigation, pulmonary embolism (PE) has continued to pose a diagnostic and management challenge worldwide. Aging populations, patients living with a mounting number of chronic medical conditions, particularly cancer, and increasingly prevalent health care disparities herald a growing burden of PE. In the meantime, navigating expanding strategies for immediate and long-term anticoagulation, as well as advanced therapies, including catheter-based interventions for patients with more severe PE, has become progressively daunting. Accordingly, clinicians frequently turn to evidence-based clinical practice guidelines for diagnostic and management recommendations. However, numerous international guidelines, heterogeneity in recommendations, as well as areas of uncertainty or omission may leave the readers and clinicians without a clear management pathway. In this review of international PE guidelines, we highlight key areas of consistency, difference, and lack of recommendations (silence) with an emphasis on critical clinical and research needs.

Right ventricular-pulmonary artery coupling for prognostication in acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) increases pulmonary pressure and impair right ventricular (RV) function. Echocardiographic investigation can quantify this mismatch as the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) ratio. The aim of the study was to investigate the prognostic capabilities of TAPSE/PASP ratio in patients with acute PE. METHODS: We utilized the RIETE registry to analyze consecutive hemodynamically stable PE patients. We used multivariable logistic regression analyses to assess the association between the TAPSE/PASP ratio and 30-day all-cause mortality across the strata of European Society of Cardiology (ESC) risk categories. RESULTS: We included 4,478 patients, of whom 1,326 (30%) had low-risk, 2,425 (54%) intermediate-low risk, and 727 (16%) intermediate-high risk PE. Thirty-day mortality rates were 0.7%, 2.3% and 3.4%, respectively. Mean TAPSE/PASP ratio was 0.65±0.29 in low-risk patients, 0.46±0.30 in intermediate-low risk, and 0.33±0.19 in intermediate-high risk patients. In multivariable analyses, there was an inverse association between TAPSE/PASP ratio and 30-day mortality (adjusted OR 1.32 [95%CI 1.14-1.52] per 0.1 decrease in TAPSE/PASP). TAPSE/PASP ratio below optimal cut-points was associated with increased mortality in low- (<0.40, aOR: 5.88; 95%CI:1.63-21.2), intermediate-low (<0.43, aOR: 2.96; 95%CI:1.54-5.71) and intermediate-high risk patients (<0.34, aOR: 4.37; 95%CI:1.27-15.0). TAPSE/PASP <0.44 showed net reclassification improvement of 18.2% (95%CI:0.61-35.8) vs. RV/LV ratio >1, and 27.7% (95%CI:10.2-45.1) vs. ESC risk strata. CONCLUSIONS: Decreased TAPSE/PASP ratio was associated with increased mortality. The ratio may aid in clinical decision-making, particularly for intermediate-risk patients for whom the discriminatory capability of the current risk stratification tools is limited.

Coassembling Mesoporous Zeolitic Imidazolate Frameworks by Directed Reticular Chemistry.

Conventional microporous zeolitic imidazolate frameworks (ZIFs) face limitations in mass transfer and pore accessibility when dealing with large guest molecules. Here, we describe a technique for the synthesis of mesoporous ZIFs (MesoZIFs) using a strategy we term directed reticular chemistry. MesoZIF-8 was prepared through solvent evaporation-induced coassembly of polystyrene-block-poly(ethylene oxide) (PS-b-PEO), ZIF-8 building blocks, and acetic acid (AcOH), followed by amine-facilitated crystallization of ZIF-8 in the interstices of PS-b-PEO micelles. AcOH prevents the fast coordination of ZIF-8 building blocks, avoiding phase separation during coassembly. The employed amine plays a crucial role in neutralizing the crystallization environment and further deprotonating the 2-methlyimizale linker to coordinate with zinc ions. Ink bottle-shaped mesopores with tunable mesopore sizes were created by adjusting the molecular weight of PS-b-PEO. Compared to microporous ZIF-8, MesoZIF-8 exhibited enhanced performance in Knoevenagel condensation reactions involving large reactants and hydrogen storage capacity. With this study, we establish an efficient approach for synthesizing MesoZIFs with highly accessible mesopores to enhance ZIF performance in targeted applications.

Pulmonary embolism work-up in chronic obstructive pulmonary disease exacerbations: what is the best strategy for clinicians?

PURPOSE OF REVIEW: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the natural course of COPD, as they increase morbidity and mortality. Acute pulmonary embolism may mimic the symptoms of COPD exacerbations. However, the exact prevalence of pulmonary embolism in unexplained exacerbations of COPD is unclear based on the current data. This review provides a practical approach to patients with COPD complaining of worsening respiratory symptoms. RECENT FINDINGS: A randomized clinical trial has shown that a routine pulmonary embolism diagnostic work-up does not improve care of patients with acute exacerbations of COPD. However, review of the recent literature suggests that a nonnegligible proportion of otherwise unexplained exacerbations of COPD may be caused by pulmonary embolism. To date, nevertheless, there are limited studies developing and validating clinical models that might aid in the identification of patients requiring additional tests for the diagnosis of pulmonary embolism. SUMMARY: Until new evidence becomes available, we believe that a routine diagnostic strategy for pulmonary embolism is not appropriate for patients with acute exacerbations of COPD. Recommendations for routine pulmonary embolism diagnostic work-up necessitate further development of prognostic models and conduct of clinical trials that assess important health outcomes.

Glucocorticoid Receptor Signaling Is Critical for Mouse Corneal Development, Inhibition of Inflammatory Response, and Neovascularization of the Cornea.

The cornea protects the interior of the eye from external agents such as bacteria, viruses, and debris. Synthetic glucocorticoids are widely prescribed in the treatment of ocular infections and disorders. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR); however, the molecular and physiological functions of GR signaling in the cornea are poorly understood. This study found that treatment of mice with glucocorticoid eye drops led to a profound regulation of the corneal transcriptome. These glucocorticoid-regulated genes were associated with multiple biological functions, including the immune response. To understand the direct role of GR signaling in the cornea, mice with conditional knockout of GRs in the corneal epithelium were generated. Mice lacking corneal GRs exhibited microphthalmia, loss of pupils, a deformed and opaque lens, and mislocalization of key structural proteins within the corneal epithelial layers. Global transcriptomic approaches revealed that loss of GR signaling in the cornea also resulted in the dysregulation of a large cohort of genes strongly associated with an enhanced inflammatory response. Finally, corneal GR signaling was required for preventing neovascularization of blood and lymphatic vessels and thereby immune cell infiltration of the cornea. These results reveal that corneal GR signaling plays a critical role in ocular development and in maintaining the homeostasis of the eye.

Rate of recurrence after discontinuing anticoagulation in patients with venous thromboembolism within 30 days after COVID-19 vaccine.

This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event.

Prophylaxis of venous thromboembolism in hospitalized patients admitted from Spanish emergency departments: the PROTESU II study. / Profilaxis de la enfermedad tromboembólica venosa en pacientes hospitalizados por patología médica desde los servicios de urgencias españoles: estudio PROTESU II.

OBJECTIVE: To estimate the prevalence of inappropriate use of prophylaxis to prevent venous thromboembolism (VTE) in patients with medical diseases admitted to hospital from the emergency department. To explore variables associated with inappropriate thromboprophylaxis. METHODS: Prospective multicenter cohort study in 15 hospital emergency departments. We included patients admitted for a medical condition during 7 days in the first quarter of 2022. We assessed risk for VTE with the Padua Prediction Score (PPS). Inappropriate thromboprophylaxis was defined by failure to prescribe prophylaxis in patients with a high-risk PPS assessment unless there were absolute contraindications (active bleeding or severe thrombopenia) or, alternatively, the prescription of prophylaxis in patients with a low-risk PPS assessment or absolute contraindications. A logistic regression model was adjusted for risk level to identify variables associated with inappropriate use of thromboprophylaxis. RESULTS: Of a total of 630 patients included, 450 (71.4%) had PPS scores indicating high risk for VTE; 180 patients were at low risk. Thromboprophylaxis was inappropriate in 248 patients (39.4%): 165 high-risk patients who received no prophylaxis, 82 low-risk patients who were nonetheless treated, and 1 patient who was treated in spite of severe thrombopenia. Odds ratios (ORs) revealed that the variables associated with inappropriate use of thromboprophylaxis were trauma or recent surgery (OR, 5.53; 95% CI, 1.58-19.34), presence of factors indicating risk for bleeding (OR, 2.61; 95% CI, 1.44-4.73), and hospital admission for either urinary tract infection (OR, 2.29; 95% CI, 1.07-4.87) or gastrointestinal disease (OR, 4.30; 95% CI, 1.71-10.85). CONCLUSIONS: The inappropriate use of thromboprophylaxis in Spanish emergency departments is high and associated with certain clinical characteristics.

OBJETIVO: Evaluar la inadecuación de la tromboprofilaxis farmacológica, según la escala Padua (PPS), para prevenir la enfermedad tromboembólica venosa (ETV) entre los pacientes que ingresan desde el servicio de urgencias hospitalario (SUH) por patología médica, así como las variables asociadas a su uso inadecuado. METODO: Estudio de cohortes, prospectivo, multicéntrico donde participaron 15 SUH. Se incluyeron los pacientes atendidos que requirieron ingreso por enfermedad médica durante 7 días del primer trimestre de 2022. La inadecuación de la tromboprofilaxis farmacológica se definió como la no utilización en pacientes clasificados por PPS de alto riesgo sin contraindicaciones absolutas para su uso (hemorragia activa o trombopenia grave) o su utilización en pacientes de riesgo bajo o con contraindicaciones absolutas. Se ajustó, para cada grupo de riesgo, un modelo de regresión logística para identificar las variables asociadas a la inadecuación. RESULTADOS: Se incluyeron 630 pacientes, 450 (71,4%) tenían riesgo alto y 180 (28,6%) riesgo bajo para ETV según la PPS. De ellos, la tromboprofilaxis fue inadecuada en 248 pacientes (39,4%) (165 tenían riesgo alto pero no recibieron tromboprofilaxis, 1 la recibió teniendo trombopenia grave y 82 tenían riesgo bajo pero recibieron tromboprofilaxis). Las variables asociadas con la inadecuación en pacientes de alto riesgo fueron trauma o cirugía recientes con odds ratio (OR) de OR 5,53 (IC 95%: 1,58-19,34), presencia de factores de riesgo hemorrágico con OR de 2,61 (IC 95%: 1,44-4,73), e infección del tracto urinario con OR de 2,29 (IC 95%: 1,07-4,87) y enfermedad gastrointestinal con OR de 4,30 (IC 95%: 1,71-10,85) como motivos de ingreso. CONCLUSIONES: En los SUH españoles, el uso inadecuado de la tromboprofilaxis farmacológica es elevado. Algunas características clínicas se asocian al uso inadecuado de dicha tromboprofilaxis.

Mechanical force of uterine occupation enables large vesicle extrusion from proteostressed maternal neurons.

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate the extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here, we document that mechanical force can significantly potentiate exopher extrusion from proteostressed neurons. Exopher production from the C. elegans ALMR neuron peaks at adult day 2 or 3, coinciding with the C. elegans reproductive peak. Genetic disruption of C. elegans germline, sperm, oocytes, or egg/early embryo production can strongly suppress exopher extrusion from the ALMR neurons during the peak period. Conversely, restoring egg production at the late reproductive phase through mating with males or inducing egg retention via genetic interventions that block egg-laying can strongly increase ALMR exopher production. Overall, genetic interventions that promote ALMR exopher production are associated with expanded uterus lengths and genetic interventions that suppress ALMR exopher production are associated with shorter uterus lengths. In addition to the impact of fertilized eggs, ALMR exopher production can be enhanced by filling the uterus with oocytes, dead eggs, or even fluid, supporting that distention consequences, rather than the presence of fertilized eggs, constitute the exopher-inducing stimulus. We conclude that the mechanical force of uterine occupation potentiates exopher extrusion from proximal proteostressed maternal neurons. Our observations draw attention to the potential importance of mechanical signaling in extracellular vesicle production and in aggregate spreading mechanisms, making a case for enhanced attention to mechanobiology in neurodegenerative disease.

Neurons are specialized cells in the brain and nervous system that transmit signals between the brain and the rest of the body, enabling humans and animals to react to internal and external stimuli. For this communication system to function effectively, neurons must remain healthy. Neurons maintain their function in a variety of ways, including by removing excess or damaged cellular components (such as organelles and protein aggregates) that could compromise neuron function. One way to do this is by extruding organelles and aggregates. During 'extrusion events', the material to be removed is gathered within a budding portion of the plasma membrane, which forms a vesicle that ejects the material from the neuron. However, the factors driving the extrusion process remained unknown. To investigate, Wang, Guasp, Salam et al. conducted experiments in the roundworm Caenorhabditis elegans, finding that the number of extrusion events in a certain type of neuron increases at the peak of reproduction. More specifically, a greater number of extrusion events were associated with the presence of fertilized eggs, which accumulate in the uterus before they are laid. Disrupting eggs, sperm or the fertilization process suppressed the increase in extrusion events, suggesting the presence of fertilized eggs is responsible. To determine how the eggs might trigger extrusion events, Wang et al. stretched the uterus using dead eggs, unfertilized eggs or by injecting fluid, finding that each of these approaches increased the number of extrusion events. Further analysis suggests that this mechanical stretching of the uterus signals to the neurons that reproduction has started, encouraging the neurons to remove old components and optimize their function. Wang et al. hypothesize that this stretch response could support neuronal behaviors that aid in successful reproduction, such as sensing food and selecting where to lay eggs. The findings increase our understanding of the factors that trigger vesicle extrusion in living organisms. These observations could have implications for human neurodegenerative diseases such as Alzheimer's disease, in which protein aggregates accumulate in neurons. It is possible that mechanical signals generated by factors associated with Alzheimer's disease, such as high blood pressure, could influence neuronal extrusion and contribute to some of the mechanisms underlying aggregate transfer in neurodegenerative diseases.

Acetabular morphology variations in a Hispanic population.

BACKGROUND: Rotational abnormalities of the hip have been implicated in the etiology of diseases, such as hip dysplasia, osteoarthritis, and femoroacetabular impingement. Despite the extensive literature on hip morphology, there is a gap in knowledge regarding variations in the Hispanic population. PURPOSE: To describe the bony anatomy variations of the acetabulum in a Hispanic population. MATERIAL AND METHODS: This is a cross-sectional study. We studied 182 computed tomography (CT) images in patients aged older than 21 years, who had undergone pelvic CT for any condition, except hip fracture. Measurements of acetabular version, anterior and posterior acetabular sector angles (AASA/PASA) and horizontal acetabular sector angles (HASA) were made. Acetabular variations were then compared to weight and sex data. RESULTS: The mean acetabular anteversion was greater in women (P < 0.001). Women exhibited a greater PASA (P < 0.05); however, men had a greater AASA (P < 0.05). Underweight individuals had a smaller PASA (P < 0.01) and HASA (P < 0.05) than individuals with a normal weight. CONCLUSION: The Hispanic hip is morphologically similar to other populations previously reported in the literature; however, Hispanic men have less coverage of the femoral head by the posterior acetabular wall when compared to women of the same ethnicity. These abnormalities have a direct impact on management and surgical approach in patients treated for femoroacetabular impingement and hip dysplasia.

Risk stratification of acute pulmonary embolism.

Risk stratification of patients with acute pulmonary embolism (PE) assists with the selection of appropriate initial therapy and treatment setting. Patients with acute symptomatic PE that present with arterial hypotension or shock have a high risk of death, and treatment guidelines recommend strong consideration of reperfusion in this setting. For haemodynamically stable patients with PE, the combination of a negative clinical prognostic score and the absence of computed tomography-assessed right ventricle enlargement may accurately identify those at low-risk of short-term complications after the diagnosis of PE, and such patients might benefit from an abbreviated hospital stay or outpatient therapy. Some evidence suggests that the accumulation of factors indicating worse outcomes from PE on standard anticoagulation identifies the more severe stable patients with acute PE who might benefit from intensive monitoring and recanalization procedures, particularly if haemodynamic deterioration occurs. Current risk classifications have several shortcomings that might adversely affect clinical and healthcare decisions. Ongoing initiatives aim to address many of those shortcomings, and will hopefully help optimize risk stratification algorithms and treatment strategies.

Duration of anticoagulation of venous thromboembolism.

Venous thromboembolism (VTE) is a common, serious condition that requires anticoagulation for at least three months to prevent recurrence and long-term complications. After this initial period, the decision to continue or stop anticoagulation depends on the balance between the risk of recurrent VTE and the risk of bleeding. Established guidelines suggest short-term anticoagulation for VTE caused by transient factors and indefinite anticoagulation for recurrent or cancer-associated VTE. However, for a first unprovoked VTE, decision-making remains challenging. Current predictive scores for recurrence and bleeding are not sufficiently reliable, and the safety and efficacy of reduced-dose anticoagulation remain unclear. In the future, precision and patient-centred medicine may improve treatment decisions in this area.

Predictors of pulmonary embolism in chronic obstructive pulmonary diseases patients admitted for worsening respiratory symptoms: An individual participant data meta-analyses.

BACKGROUND: Pulmonary embolism (PE) and acute exacerbation of chronic obstructive pulmonary disease (COPD) have similar clinical symptoms, making PE diagnosis challenging. Previous studies have shown that the prevalence of PE among COPD patients admitted with worsening respiratory symptoms was not negligible, but that systematic search for PE did not provide a clinical benefit. Predictive factors for PE remain unknown. OBJECTIVE: to identify predictive factors for PE among COPD patients with worsening respiratory symptoms. METHODS: We conducted an individual participant data meta-analysis which included the patients from the prospective PEP cohort and those randomized to the intervention arm in the SLICE trial which included a systematic search for PE in COPD patients admitted for worsening respiratory symptoms. Univariable and multivariable analysis were used to assess factors associated with the diagnosis of PE during the initial management. RESULTS: Among 1110 COPD patients, PE was diagnosed in 61 (5.49 %; 95 %CI 4.15 %-6.84 %). In univariable analysis, BNP (Brain natriuretic peptide) (odds ratio [OR] 1.02 per 100 ng/L increase, 95 %CI 1.01-1.04), prothrombin time (OR 0.78, 95 %CI 0.65-0.94), fibrinogen (OR 0.80, 95 %CI 0.64-0.98), atrial fibrillation (OR 4.74, 95 %CI 1.84-10.80), respiratory rate ≥30 min (OR 2.34, 95 %CI 1.13-4.6) and recent medical immobilization (OR 1.79, 95 %CI 0.99-3.13]) were associated with the risk of PE diagnosed during the initial management. In multivariable analysis, respiratory rate ≥30 (OR 2.77, 95 %CI 1.08-6.71) was a predictive factor for PE, as well as BNP (OR 1.02, 95 %CI 1.00-1.05) with an area under the curve =0.64, negative predictive value =0.15 (95 %CI 0.09-0.23), sensitivity =0.78 (95 %CI 0.74-0.82) and specificity =0.46 (95 %CI 0.29-0.63). CONCLUSION: Among patients with COPD admitted for worsening respiratory symptoms, respiratory rate and BNP levels are predictor of PE, but with limited discriminatory power.

Intraoperative Intracranial Pressure Changes in Children With Craniosynostosis Undergoing Endoscopic-Assisted Strip Craniectomy.

BACKGROUND AND OBJECTIVES: Craniosynostosis can lead to progressive cranial and skull base deformities and can be associated with increased intracranial pressure (ICP), ophthalmological manifestations, behavioral changes, and developmental delay. Most published data on the incidence of elevated ICP include older children undergoing open surgical correction. Endoscopic-assisted release of fused sutures with postoperative helmet therapy is an established method for managing craniosynostosis presenting at an early age; however, the immediate effect of this approach on ICP in a young cohort has not been previously reported. METHODS: Prospective data on 52 children undergoing endoscopic-assisted release of stenosed cranial sutures were included. Individuals were excluded if they underwent open correction or had previous cranial surgery. Individuals underwent a standardized endoscopic approach for each suture type. ICP was measured using an intraparenchymal sensor both before creation of the neosuture and after complete release of the stenosed suture. An ICP reading of >10 mm Hg was considered elevated. RESULTS: The mean age was 5.3 months, range 1 to 32 months, and 94% was younger than 12 months. The mean opening pressure was 12.7 mm Hg, and the mean closing pressure was 2.9 mm Hg. Opening ICP ≥10 mm Hg was present in 58%, ≥15 mm Hg was present in 31%, and ≥20 mm Hg was present in 23%. No patient had an ICP above 10 mm Hg at closing. The mean percentage change in ICP among all craniosynostosis cases was a 64% decrease. Optic disk swelling was identified in 28 children preoperatively and improved in 22 children at follow-up. CONCLUSION: Elevated ICP may occur in infants with craniosynostosis at higher rates than previously reported. Endoscopic-assisted craniectomy has an immediate effect on lowering ICP and improving postoperative ophthalmological findings.

Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

STOP-Bang questionnaire in patients hospitalized with acute symptomatic pulmonary embolism.

STUDY OBJECTIVES: The STOP-Bang questionnaire is a validated screening tool for obstructive sleep apnea (OSA). We conducted this study to validate it among patients hospitalized with acute symptomatic pulmonary embolism (PE). METHODS: This prospective cohort study enrolled consecutive stable patients with acute PE who underwent an overnight sleep study within 7 days after diagnosis. Our outcomes were: i) the STOP-Bang questionnaire's utility for risk stratification, ii) the discrimination of the STOP-Bang questionnaire categories, iii) the false negative rate of STOP-Bang questionnaire prediction, and iv) the clinical utility of the STOP-Bang questionnaire to exclude OSA. We also calculated the test performance characteristics to predict OSA. RESULTS: During the study period, 268 patients completed a sleep study. OSA was found in 47% of patients. OSA incidence in low-, moderate-, and high-risk STOP-Bang groups was 22.4%, 48.2%, and 61.5%, respectively (P <0.001). The area under the receiver operating characteristics curve of the STOP-Bang questionnaire for risk of OSA was 0.65. The false negative rate of a low-risk STOP-Bang questionnaire result to rule out OSA was 22.4% and the clinical utility was 21.6%. The sensitivity was 89.8% (97.2% for men and 80.4% for women). CONCLUSIONS: The STOP-Bang questionnaire showed poor discrimination for the risk of OSA in hospitalized patients with acute symptomatic PE. It had a high false negative rate and a low clinical utility. The STOP-Bang questionnaire had a good sensitivity in men, and might be used to rule out OSA in this population.

Chronic thromboembolic pulmonary hypertension treatment and sex: Systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic pulmonary hypertension leading to right heart failure and death. While pulmonary endarterectomy is the treatment of choice, some patients might benefit from medical therapy or balloon pulmonary angioplasty. Sex differences in outcomes of these therapies are not well characterized. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis to investigate sex differences in outcomes of various therapies for CTEPH. We searched MEDLINE, PubMed, Embase, CINAHL and the Cochrane Library databases between January 1, 2010 and April 30, 2021, published in English. We pooled incidence estimates using random-effects meta-analyses. We evaluated heterogeneity using the I2 statistic. We assessed publication bias using Begg's and Egger's tests. This study is registered in PROSPERO, CRD42021268504. RESULTS: A total of 19 studies met the eligibility criteria, but only 3 trials provided separate outcomes for women and men. Two studies evaluated the efficacy of BPA, and one study evaluated the efficacy of riociguat (129 patients). Overall, 57.3% of patients were women and 62.6% were in functional class III. Mean time of follow-up was 55.5 (SD 26.1) weeks. Women showed a significantly better response in cardiac index (mean difference [MD], 0.10L/min/m2; 95% confidence interval [CI], 0.04-0.16; I2=0%; P=0.001). Alternatively, the reduction of pulmonary vascular resistances was significantly higher for men than for women (MD, 161.17dynscm-5; 95% CI, 67.99-254.35; I2=0%; P=0.0007). CONCLUSIONS: Women and men might show different hemodynamic responses to riociguat or BPA for CTEPH.