Insights into Pathogenesis of Trachoma.

Trachoma is the most common infectious cause of blindness worldwide. This review investigates the pathogenesis of trachoma, focusing on its causative agent, transmission pathways, disease progression, and immune responses. Trachoma is caused by serovars A-C of the bacterium Chlamydia trachomatis (Ct). Transmission occurs through direct or indirect exchanges of ocular and nasal secretions, especially in regions with poor hygiene and overcrowded living conditions. The disease is initiated in early childhood by repeated infection of the ocular surface by Ct. This triggers recurrent chronic inflammatory episodes, leading to the development of conjunctival scarring and potentially to trichiasis, corneal opacity, and visual impairment. Exploring the pathogenesis of trachoma not only unveils the intricate pathways and mechanisms underlying this devastating eye disease but also underscores the multifaceted dimensions that must be considered in its management.

Incidence and impact of venous thromboembolism in hospitalized patients with acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) and venous thromboembolism (VTE) remain common and potentially lethal disease entities. AP might be an important trigger of systemic inflammtion and may activate the coagulation system with increased VTE risk. METHODS: The German nationwide inpatient sample was screened for patients admitted due to AP (ICD-code K85) 2005-2019. AP hospitalizations were stratified for VTE as well as risk-factors and the impact of VTE on in-hospital case-fatality rate were investigated. RESULTS: Overall, 797,364 hospitalizations of patients due to AP (aged in median 56.0 [IQR 44.0-71.0] years), 39.2 % females) were detected in Germany 2005-2019. Incidence of VTE in hospitalized AP patients was 1764.8 per 100,000 hospitalizations (1.8 %) with highest VTE rate between 5th and 6th decade. Cancer (OR 1.656 [95 %CI 1.513-1.812], P < 0.001), any surgery (OR 4.063 [95 %CI 3.854-4.284], P < 0.001), and heart failure (OR 1.723 [95 %CI 1.619-1.833], P < 0.001) were independently associated with VTE occurrence. Case-fatality (8.8 % vs. 2.7 %, P < 0.001) was more than 3-fold higher in AP patients with than without VTE. VTE was associated with increased case-fatality in AP patients (OR 3.925 [95 %CI 3.684-4.181], P < 0.001). CONCLUSIONS: VTE is a life-threatening event in hospitalized AP patients associated with an almost 4-fold increased case-fatality rate. Cancer, any surgery, thrombophilia and heart failure were important risk factors for occurrence of VTE in AP.

Estimated Annual Healthcare Costs After Acute Pulmonary Embolism: Results From a Prospective Multicentre Cohort Study.

OBJECTIVE: Patients surviving acute pulmonary embolism (PE) necessitate long-term treatment and follow-up. However, the chronic economic impact of PE on European healthcare systems remains to be determined. METHODS AND RESULTS: We calculated the direct cost of illness during the first year after discharge for the index PE, analyzing data from a multicentre prospective cohort study in Germany. Main and accompanying readmission diagnoses were used to calculate DRG-based hospital reimbursements; anticoagulation costs were estimated from the exact treatment duration and each drug's unique national identifier; and outpatient post-PE care costs from guidelines-recommended algorithms and national reimbursement catalogues. Of 1017 patients enrolled at 17 centres, 958 (94%) completed ≥ 3-month follow-up; of those, 24% were rehospitalized (0.34 [95% CI 0.30-0.39] readmissions per PE survivor). Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis of 837 patients with complete 12-month follow-up) cancer, but not recurrent PE, were independent cost predictors by hurdle gamma regression accounting for zero readmissions. Estimated rehospitalization cost was €1138 (95% CI 896-1420) per patient. Anticoagulation duration was 329 (IQR 142-365) days, with estimated average per-patient costs of €1050 (median 972; IQR 458-1197); costs of scheduled ambulatory follow-up visits amounted to €181. Total estimated direct per-patient costs during the first year after PE ranged from €2369 (primary analysis) to €2542 (sensitivity analysis). CONCLUSIONS: By estimating per-patient costs and identifying cost drivers of post-PE care, our study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved cardiovascular prevention. (Trial registration number: DRKS00005939).

Extracorporeal Membrane Oxygenation and Reperfusion Strategies in High-Risk Pulmonary Embolism Hospitalizations.

OBJECTIVES: To investigate the contemporary use of extracorporeal membrane oxygenation (ECMO) in conjunction with reperfusion strategies in high-risk pulmonary embolism (PE). DESIGN: Observational epidemiological analysis. SETTING: The U.S. Nationwide Inpatient Sample (NIS) (years 2016-2020). PATIENTS: High-risk PE hospitalizations. MEASUREMENTS AND MAIN RESULTS: Use of ECMO in conjunction with thrombolysis-based reperfusion (systemic thrombolysis or catheter-directed thrombolysis) or mechanical reperfusion (surgical embolectomy or catheter-based thrombectomy) with regards to in-hospital mortality and major bleeding. We identified high-risk PE hospitalizations in the NIS (years 2016-2020) and investigated the use of ECMO in conjunction with thrombolysis-based (systemic thrombolysis or catheter-directed thrombolysis) and mechanical (surgical embolectomy or catheter-based thrombectomy) reperfusion strategies with regards to in-hospital mortality and major bleeding. Among 122,735 hospitalizations for high-risk PE, ECMO was used in 2,805 (2.3%); stand-alone in 1.4%, thrombolysis-based reperfusion in 0.4%, and mechanical reperfusion in 0.5%. Compared with neither reperfusion nor ECMO, ECMO plus thrombolysis-based reperfusion was associated with reduced in-hospital mortality (adjusted odds ratio [aOR] 0.61; 95% CI, 0.38-0.98), whereas no difference was found with ECMO plus mechanical reperfusion (aOR 1.03; 95% CI, 0.67-1.60), and ECMO stand-alone was associated with increased in-hospital mortality (aOR 1.60; 95% CI, 1.22-2.10). In the cardiac arrest subgroup, ECMO was associated with reduced in-hospital mortality (aOR 0.71; 95% CI, 0.53-0.93). Among all patients on ECMO, thrombolysis-based reperfusion was significantly associated (aOR 0.55; 95% CI, 0.33-0.91), and mechanical reperfusion showed a trend (aOR 0.75; 95% CI, 0.47-1.19) toward reduced in-hospital mortality compared with no reperfusion, without increases in major bleeding. CONCLUSIONS: In patients with high-risk PE and refractory hemodynamic instability, ECMO may be a valuable supportive treatment in conjunction with reperfusion treatment but not as a stand-alone treatment especially for patients suffering from cardiac arrest.

Lipid lowering for prevention of venous thromboembolism: a network meta-analysis.

BACKGROUND AND AIMS: Studies have suggested that statins may be associated with reduced risk of venous thromboembolism (VTE). The aim of the current study was to assess the evidence regarding the comparative effect of all lipid-lowering therapies (LLT) in primary VTE prevention. METHODS: After a systematic search of PubMed, CENTRAL, and Web of Science up until 2 November 2022, randomized controlled trials (RCT) of statins (high- or low-/moderate-intensity), ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were selected. An additive component network meta-analysis to compare VTE risk during long-term follow-up across different combinations of LLT was performed. RESULTS: Forty-five RCTs (n = 254 933 patients) were identified, reporting a total of 2084 VTE events. Compared with placebo, the combination of PCSK9i with high-intensity statin was associated with the largest reduction in VTE risk (risk ratio [RR] 0.59; 95% confidence interval [CI] 0.43-0.80), while there was a trend towards reduction for high-intensity (0.84; 0.70-1.02) and low-/moderate-intensity (0.89; 0.79-1.00) statin monotherapy. Ezetimibe monotherapy did not affect the VTE risk (1.04; 0.83-1.30). There was a gradual increase in the summary effect of VTE reduction with increasing intensity of the LLT. When compared with low-/moderate-intensity statin monotherapy, the combination of PCSK9i and high-intensity statin was significantly more likely to reduce VTE risk (0.66; 0.49-0.89). CONCLUSIONS: The present meta-analysis of RCTs suggests that LLT may have a potential for VTE prevention, particularly in high-intensity dosing and in combination therapy.

Rhythm vs Rate Control Strategy for Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Rhythm control, either with antiarrhythmic drugs or catheter ablation, and rate control strategies are the cornerstones of atrial fibrillation (AF) management. Despite the increasing role of rhythm control over the past few years, it remains inconclusive which strategy is superior in improving clinical outcomes. OBJECTIVES: This study summarizes the total and time-varying evidence regarding the efficacy of rhythm- vs rate-control strategies in the management of AF. METHODS: We systematically perused the MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science databases for randomized controlled trials from inception to November 2023. We included studies that compared the efficacy of rhythm control (ie, antiarrhythmic drugs classes Ia, Ic, or III, AF catheter ablation, and electrical cardioversion) and rate control (ie, beta-blocker, digitalis, or calcium antagonist) strategies among patients with nonvalvular AF. The primary outcome was cardiovascular (CV) death, whereas secondary outcomes included all-cause death, stroke, hospitalization for heart failure (HF), sinus rhythm at the end of the follow-up, and rhythm control-related adverse events. A cumulative meta-analysis to assess temporal trends and a meta-regression analysis using the percentage of ablation use was performed. RESULTS: We identified 18 studies with a total of 17,536 patients (mean age: 68.6 ± 9.7 years, 37.9% females) and a mean follow-up of 28.5 months. Of those, 31.9% had paroxysmal AF. A rhythm control strategy reduced CV death (HR: 0.78; 95% CI: 0.62-0.96), stroke (HR: 0.801; 95% CI: 0.643-0.998), and hospitalization for HF (HR: 0.80; 95% CI: 0.69-0.94) but not all-cause death (HR: 0.86; 95% CI: 0.73-1.02) compared with a rate control strategy. This benefit was driven by contemporary studies, whereas more ablation use within the rhythm control arm was associated with improved outcomes, except stroke. CONCLUSIONS: In patients with AF, a contemporary rhythm control strategy leads to reduced CV mortality, HF events, and stroke compared with a rate control strategy.

Diagnosis of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: data from a practice-based longitudinal cohort.

BACKGROUND: A large prospective multicenter cohort study with systematic follow-up recently reported a 2.3% 2-year cumulative incidence of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE). OBJECTIVES: The present investigation aimed to determine the reported prevalence and incidence of CTEPH diagnosis after acute PE in real-world practice over a 12-year period. METHODS: This study was based on nationwide ambulatory billing claims and drug prescription data of all residents with public health insurance in Germany from 2010 to 2021. RESULTS: A total of 573 972 patients with acute PE (median age, 71 years; 57.4% women) were identified between 2010 and 2021. Prevalence of CTEPH among patients with history of PE increased during the period from 0.4% in 2010 to 0.9% in 2021. CTEPH was diagnosed in 2556 patients after acute PE, with most (17.6%) diagnoses reported within the first 3 months after the index PE event. The cumulative incidence rate after 3 months (first quarter) was calculated at 0.08% and after the first 2 years (eighth quarter) at 0.36%; it was 0.75% over the entire (90-month) follow-up period. Patients with CTEPH diagnosis during follow-up more often had right ventricular dysfunction at the index acute PE (14.9% vs 8.3%; P < .001). CONCLUSION: The low CTEPH incidence rate after acute PE in the present analysis suggests low awareness of CTEPH. It further suggests a lack of systematic follow-up protocols for acute PE survivors in the real world. Improved implementation of existing recommendations on follow-up strategies after PE is warranted.

Drivers and recent trends of hospitalisation costs related to acute pulmonary embolism.

BACKGROUND AND AIMS: The socio-economic burden imposed by acute pulmonary embolism (PE) on European healthcare systems is largely unknown. We sought to determine temporal trends and identify cost drivers of hospitalisation for PE in Germany. METHODS AND RESULTS: We analysed the totality of reimbursed hospitalisation costs in Germany (G-DRG system) in the years 2016-2020. Overall, 484 884 PE hospitalisations were coded in this period. Direct hospital costs amounted to a median of 3572 (IQR, 2804 to 5869) euros, resulting in average total reimbursements of 710 million euros annually. Age, PE severity, comorbidities and in-hospital (particularly bleeding) complications were identified by multivariable logistic regression as significant cost drivers. Use of catheter-directed therapy (CDT) constantly increased (annual change in the absolute proportion of hospitalisations with CDT + 0.40% [95% CI + 0.32% to + 0.47%]; P < 0.001), and it more than doubled in the group of patients with severe PE (28% of the entire population) over time. Although CDT use was overall associated with increased hospitalisation costs, this association was no longer present (adjusted OR 1.02 [0.80-1.31]) in patients with severe PE and shock; this was related, at least in part, to a reduction in the median length of hospital stay (for 14.0 to 8.0 days). CONCLUSIONS: We identified current and emerging cost drivers of hospitalisation for PE, focusing on severe disease and intermediate/high risk of an adverse early outcome. The present study may inform reimbursement decisions by policymakers and help to guide future health economic analysis of advanced treatment options for patients with PE.

The Current Evidence of Pulmonary Embolism Response Teams and Their Role in Future.

Acute pulmonary embolism (PE) remains a critical medical condition requiring prompt and accurate management. The introduction and growing significance of pulmonary embolism response teams (PERT), also termed EXPERT-PE teams, signify a paradigm shift toward a collaborative, multidisciplinary approach in managing this complex entity. As the understanding of acute PE continues to evolve, PERTs stand as a linkage of optimized care, offering personalized and evidence-based management strategies for patients afflicted by this life-threatening condition. The evolving role of PERTs globally is evident in their increasing integration into the standard care pathways for acute PE. These teams have demonstrated benefits such as reducing time to diagnosis and treatment initiation, optimizing resource utilization, and improving patient outcomes.

Arterial Stiffness and Aortic Aneurysmal Disease - A Narrative Review.

It has been documented that large-artery stiffness is independently associated with increased cardiovascular risk and may potentially lead to heart and kidney failure and cerebrovascular disease. A systematic review of studies investigating changes in arterial stiffness in patients undergoing endovascular repair of aortic disease was conducted. In addition, a review of the available literature was performed, analyzing findings from studies using the cardio-ankle vascular index (CAVI) as a marker of arterial stiffness. Overall, 26 studies were included in the present analysis. Our research revealed a high heterogeneity of included studies regarding the techniques used to assess the aortic stiffness. Aortic stiffness was assessed by pulse wave velocity (PWV), elastic modulus (Ep), and augmentation index (AI). Currently a few studies exist investigating the role of CAVI in patients having an aortic aneurysm or undergoing endovascular aortic repair. The majority of studies showed that the treatment of an abdominal aortic aneurysm (AAA) either with open repair (OR) or endovascular aortic repair (EVAR) reduces aortic compliance significantly. Whether EVAR reconstruction might contribute a higher effect on arterial stiffness compared to OR needs further focused research. An increase of arterial stiffness was uniformly observed in studies investigating patients following thoracic endovascular aortic repair (TEVAR), and the effect was more pronounced in young patients. The effects of increased arterial stiffness after EVAR and TEVAR on the heart and the central hemodynamic, and an eventual effect on cardiac systolic function, need to be further investigated and evaluated in large studies and special groups of patients.

Modelling costs of interventional pulmonary embolism treatment: implications of US trends for a European healthcare system.

AIMS: Catheter-directed treatment (CDT) of acute pulmonary embolism (PE) is entering a growth phase in Europe following a steady increase in the USA in the past decade, but the potential economic impact on European healthcare systems remains unknown. METHODS AND RESULTS: We built two statistical models for the monthly trend of proportion of CDT among patients with severe (intermediate- or high-risk) PE in the USA. The conservative model was based on admission data from the National Inpatient Sample (NIS) 2016-20 and the model reflecting increasing access to advanced treatment from the PERT™ national quality assurance database registry 2018-21. By applying these models to the forecast of annual PE-related hospitalizations in Germany, we calculated the annual number of severe PE cases and the expected increase in CDT use for the period 2025-30. The NIS-based model yielded a slow increase, reaching 3.1% (95% confidence interval 3.0-3.2%) among all hospitalizations with PE in 2030; in the PERT-based model, increase would be steeper, reaching 8.7% (8.3-9.2%). Based on current reimbursement rates, we estimated an increase of annual costs for PE-related hospitalizations in Germany ranging from 15.3 to 49.8 million euros by 2030. This calculation does not account for potential cost savings, including those from reduced length of hospital stay. CONCLUSION: Our approach and results, which may be adapted to other European healthcare systems, provide a benchmark for healthcare costs expected to result from CDT. Data from ongoing trials on clinical benefits and cost savings are needed to determine cost-effectiveness and inform reimbursement decisions.

Healthcare resource utilisation and associated costs after low-risk pulmonary embolism: pre-specified analysis of the Home Treatment of Pulmonary Embolism (HoT-PE) study.

BACKGROUND: Pulmonary embolism (PE) and its sequelae impact healthcare systems globally. Low-risk PE patients can be managed with early discharge strategies leading to cost savings, but post-discharge costs are undetermined. PURPOSE: To define healthcare resource utilisation and overall costs during follow-up of low-risk PE. METHODS: We used an incidence-based, bottom-up approach and calculated direct and indirect costs over 3-month follow-up after low-risk PE, with data from the Home Treatment of Patients with Low-Risk Pulmonary Embolism (HoT-PE) cohort study. RESULTS: Average 3-month costs per patient having suffered low-risk PE were 7029.62 €; of this amount, 4872.93 € were associated with PE, accounting to 69.3% of total costs. Specifically, direct costs totalled 3019.33 €, and of those, 862.64 € (28.6%) were associated with PE. Anticoagulation (279.00 €), rehospitalisations (296.83 €), and ambulatory visits (194.95 €) comprised the majority of the 3-month direct costs. The remaining costs amounting to 4010.29 € were indirect costs due to loss of productivity. CONCLUSION: In a patient cohort with acute low-risk PE followed over 3 months, the majority of costs were indirect costs related to productivity loss, whereas direct, PE-specific post-discharge costs were low. Effective interventions are needed to reduce the burden of PE and associated costs, especially those related to productivity loss.

Contribution of pressure and flow changes to resistance reduction after pulmonary arterial hypertension treatment: a meta-analysis of 3898 patients.

Background: Pulmonary arterial hypertension (PAH)-targeted therapies exert significant haemodynamic changes; however, systematic synthesis is currently lacking. Methods: We searched PubMed, CENTRAL and Web of Science for studies evaluating mean pulmonary artery pressure (mPAP), cardiac index/cardiac output (CI/CO) and pulmonary vascular resistance (PVR) of PAH-targeted therapies either in monotherapy or combinations as assessed by right heart catheterisation in treatment-naïve PAH patients. We performed a random-effects meta-analysis with meta-regression. Results: We included 68 studies (90 treatment groups) with 3898 patients (age 47.4±13.2 years, 74% women). In studies with small PVR reduction (<4 WU), CI/CO increase (R2=62%) and not mPAP reduction (R2=24%) was decisive for the PVR reduction (p<0.001 and p=0.36, respectively, in the multivariable meta-regression model); however, in studies with large PVR reduction (>4 WU), both CI/CO increase (R2=72%) and mPAP reduction (R2=35%) contributed significantly to the PVR reduction (p<0.001 and p=0.01, respectively). PVR reduction as a percentage of the pre-treatment value was more pronounced in the oral+prostanoid intravenous/subcutaneous combination therapy (mean difference -50.0%, 95% CI -60.8- -39.2%), compared to oral combination therapy (-41.7%, -47.6- -35.8%), prostanoid i.v./s.c. monotherapy (-31.8%, -37.6- -25.9%) and oral monotherapy (-21.6%, -25.4- -17.8%). Changes in haemodynamic parameters were significantly associated with changes in functional capacity of patients with PAH as expressed by the 6-min walking distance. Conclusion: Combination therapies, especially with the inclusion of parenteral prostanoids, lead to remarkable haemodynamic improvement in treatment-naïve PAH patients and may unmask the contribution of mPAP reduction to the overall PVR reduction in addition to the increase in CO.

Pharmacological Treatments in Heart Failure With Mildly Reduced and Preserved Ejection Fraction: Systematic Review and Network Meta-Analysis.

BACKGROUND: Medical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with reduced ejection fraction, despite recent trials with an angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2is). OBJECTIVES: The authors aimed to estimate the aggregate therapeutic benefit of drugs for HFmrEF and HFpEF. METHODS: The authors performed a systematic review of MEDLINE, CENTRAL, and Web of Science for randomized trials including patients with heart failure (HF) and left ventricular ejection fraction (LVEF) >40%, treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (analyzed together as renin-angiotensin system inhibitors [RASi]), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, and SGLT2i. An additive component network meta-analysis was performed. The primary outcome was a composite of cardiovascular (CV) death and first hospitalization for heart failure (HHF); secondary outcomes were CV death, total HHF, and all-cause mortality. RESULTS: The authors identified 13 studies with a total of 29,875 patients and a mean LVEF of 56.3% ± 8.7%. ARNI, MRA, and SGLT2i separately, but not RASi, BB, or digoxin, reduced the primary composite outcome compared with placebo. The combination of ARNI, BB, MRA, and SGLT2i was the most effective (HR: 0.47 [95% CI: 0.31-0.70]); this was largely explained by the triple combination of ARNI, MRA, and SGLT2i (HR: 0.56 [95% CI 0.43-0.71]). Results were similar for CV death (HR: 0.63 [95% CI 0.43-0.91] for ARNI, MRA, and SGLT2i) or total HHF (HR: 0.49 [95% CI 0.33-0.71] for ARNI, MRA, and SGLT2i) alone. In a subgroup analysis, only SGLT2i had a consistent benefit among all LVEF subgroups, whereas the triple combination had the greatest benefit in HFmrEF, robust benefit in patients with LVEF 50% to 59%, and a statistically marginal benefit in patients with LVEF ≥60%. CONCLUSIONS: In patients with HF and LVEF>40%, the quadruple combination of ARNI, BB, MRA, and SGLT2i provides the largest reduction in the risk of CV death and HHF; driven by the robust effect of the triple combination of ARNI, MRA, and SGLT2i. The benefit was more pronounced in HFmrEF patients.

An overview of systematic reviews on imaging tests for diagnosis of pulmonary embolism applying different network meta-analytic methods.

PURPOSE: This study aimed to apply different methods of diagnostic test accuracy network meta-analysis (DTA-NMA) for studies reporting results of five imaging tests for the diagnosis of suspected pulmonary embolism (PE): pulmonary angiography (PA), computed tomography angiography (CTPA), magnetic resonance angiography (MRA), planar ventilation/perfusion (V/Q) scintigraphy and single-photon emission computed tomography ventilation/perfusion (SPECT V/Q). METHODS: We searched four databases (MEDLINE [via PubMed], Cochrane CENTRAL, Scopus, and Epistemonikos) from inception until June 2, 2022 to identify systematic reviews (SRs) describing diagnostic accuracy of PA, CTPA, MRA, V/Q scan and SPECT V/Q for suspected PE. Study-level data were extracted and pooled using a hierarchical summary receiver operating characteristic (HSROC) meta-regression approach and two DTA-NMA models to compare accuracy estimates of different imaging tests. Risk of bias was assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool and certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. RESULTS: We identified 13 SRs, synthesizing data from 33 primary studies and for four imaging tests (PA, CTPA, MRA and V/Q scan). The HSROC meta-regression model using PA as the reference standard showed that MRA had the best overall diagnostic performance with sensitivity of 0.93 (95% confidence interval [CI]: 0.76, 1.00) and specificity of 0.94 (95% CI: 0.84, 0.99). However, DTA-NMA models indicated that V/Q scan had the highest sensitivity, while CTPA was most specific. CONCLUSION: Selecting a different DTA-NMA method to assess multiple diagnostic tests can affect estimates of diagnostic accuracy. There is no established method, but the choice depends on the data and familiarity with Bayesian statistics.

Functional capacity and dyspnea during follow-up after acute pulmonary embolism.

BACKGROUND: Dissecting the determinants of functional capacity during long-term follow-up after acute pulmonary embolism (PE) can help to better characterize a patient population with persisting limitation. METHODS: In a prospective cohort study, consecutive unselected survivors of acute PE underwent 3- and 12-month follow-up, including six-minute walking distance (6MWD) and dyspnea assessment with the modified Medical Research Council (mMRC) scale. We used reference equations adjusting for age, sex, and anthropometric measurements to define abnormal 6MWD. RESULTS: Overall, 323 of 363 (89.0%) patients had at least one recorded 6MWD value at one year. At 3 months, the prevalence of abnormal 6MWD was 21.9% and at 12 months it was 18.3%. At 3 and 12 months, 58.8% and 52.1% with abnormal 6MWD did not report dyspnea, respectively. On average and during follow-up, 6MWD significantly improved with time, while the mMRC dyspnea scale did not. Abnormal 6MWD was associated with younger age (odds ratio per decade, 0.91; 95% CI, 0.88-0.94), higher body mass index (1.10; 1.03-1.17), smoking (3.53; 1.34-9.31), intermediate- or high-risk PE (3.21; 1.21-8.56), and higher mMRC grading (2.28; 1.59-3.27). Abnormal 6MWD at 3 months was associated with the prospectively defined endpoint of post-PE impairment (3.72; 1.50-9.28) and with poor disease-specific and generic health-related quality of life. CONCLUSION: Three months after PE, 37% of patients reported dyspnea and 22% had abnormal 6MWD. After a year, 20% still had abnormal 6MWD. Dyspnea correlated with abnormal 6MWD, but over 50% of patients with abnormal 6MWD did not report dyspnea. Abnormal 6MWD predicted subsequent post-pulmonary embolism impairment and worse long-term quality of life. CLINICAL TRIAL REGISTRATION: German Clinical Trials Register Identifier DRKS00005939.

Pulmonary vasodilators and exercise in Fontan circulation: a systematic review and meta-analysis.

OBJECTIVE: In Fontan circulation, pulmonary arterial hypertension (PAH)-targeted therapies could improve the patients' exercise capacity. This study aimed to investigate the effects of PAH agents on different exercise parameters in stable Fontan patients by synthesising evidence of randomised controlled trials (RCTs). METHODS: A systematic search of PubMed, Cochrane Central Register of Controlled Trials and Web of Science databases, as well as of ClinicalTrials.gov, was performed. Primary outcomes were specific cardiopulmonary exercise test parameters: peak oxygen uptake (peak VO2), peak heart rate (peak HR), the minute ventilation/produced carbon dioxide (VE/VCO2) slope and the oxygen uptake, both measured at the anaerobic threshold (VO2@AT). RESULTS: Five RCTs were included in the analysis including 573 Fontan patients (mean age 21.2 years, 60% male). PAH-targeted therapies did not affect peak VO2 (mean difference (MD) 0.72, 95% CI -0.25 to 1.70) or peak HR (MD -0.67, 95% CI -3.81 to 2.47), but resulted in a small, significant improvement in VO2@AT (standardised MD 0.24, 95% CI 0.02 to 0.47). VE/VCO2 slope at the anaerobic threshold was also reduced (MD -1.13, 95% CI -2.25 to -0.01). CONCLUSIONS: Although PAH-targeted therapies did not affect exercise parameters at maximal effort, they induced slight improvements in indices of submaximal effort, measured at the anaerobic threshold. Pharmacological improvement of submaximal exercise seems to be a more suitable indicator of Fontan individuals' exercise capacity. Larger RCTs, recruiting specific subpopulations and focusing also on the anaerobic threshold, are warranted to draw more robust conclusions. PROSPERO REGISTRATION NUMBER: CRD42022306674.

A multidisciplinary pulmonary embolism response team (PERT): first experience from a single center in Germany.

BACKGROUND: Over the last few years, the concept of multidisciplinary pulmonary embolism response teams (PERTs) has emerged to encounter the increasing variety and complexity in managing acute pulmonary embolism (PE). PURPOSE: To investigate PERT's composition and added clinical value in a university center in Germany. METHODS: Over 4 years (01/2019-11/2022), patients with confirmed PE were enrolled in a prospective single-center cohort study (PERT Mainz). We investigated the composition of PERT and compared, after propensity score matching, patients with acute PE before and after the initiation of PERT at our Medical University Centre. The primary outcome was in-hospital PE-related mortality. RESULTS: From 2019 to 2022, 88 patients with acute PE with a PERT decision were registered. Of those, 13 (14.8%) patients died during the in-hospital stay. Patients evaluated by a PERT had a median age of 68; 48.9% were females, and 21.7% suffered from malignancy. Right ventricular dysfunction was present in 76.1% of all patients. In total, 42.0% were classified as intermediate-high-risk PE and 11.4% as high-risk PE. First PERT contact mainly originated from emergency departments (33.3%) and intensive care units (30.0%), followed by chest pain units (21.3%) and regular wards (12.0%). The participation rate of medical specialties demonstrated that cardiologists (100%) or cardiac/vascular surgeons (98.6%) were included in almost all PERT consultations, followed by radiologists (95.9%) and anesthesiologists (87.8%). Compared to the PERT era, more patients in the pre-PERT era were classified as simplified pulmonary embolism severity index (sPESI) ≥ 1 (78.4% vs 71.6%) and as high-risk PE according to ESC 2019 guidelines (18.2% vs. 11.4%). In the pre-PERT era, low- and intermediate-low patients with PE received more frequently advanced reperfusion therapies such as systemic thrombolysis or surgical embolectomy compared to the PERT era (10.7% vs. 2.5%). Patients in the pre-PERT were found to have a considerably higher all-cause mortality and PE-related mortality rate (31.8% vs. 14.8%) compared to patients in the PERT era (22.7% vs. 13.6%). After propensity matching (1:1) by including parameters as age, sex, sPESI, and ESC risk classes, univariate regression analyses demonstrated that the PE management based on a PERT decision was associated with lower risk of all-cause mortality (OR, 0.37 [95%CI 0.18-0.77]; p = 0.009). For PE-related mortality, a tendency for reduction was observed (OR, 0.54 [95%CI 0.24-1.18]; p = 0.121). CONCLUSION: PERT implementation was associated with a lower risk of all-cause mortality rate in patients with acute PE. Large prospective studies are needed further to explore the impact of PERTs on clinical outcomes.

Robotic versus laparoscopic gastrectomy for adenocarcinoma in the US: a propensity score-matching analysis of 11,173 patients on oncological adequacy.

INTRODUCTION: Surgery remains the cornerstone treatment for gastric cancer. Previous studies have reported better lymphadenectomy with minimally invasive approaches. There is a paucity of data comparing robotic and laparoscopic gastrectomy in the US. Herein, we examined whether oncological adequacy differs between laparoscopic and robotic approaches. METHODS: The National Cancer Database was utilized to identify patients who underwent gastrectomy for adenocarcinoma between 2010 and 2019. A propensity score-matching analysis between robotic gastrectomy (RG) versus laparoscopic gastrectomy (LG) was performed. The primary outcomes were lymphadenectomy ≥ 16 nodes and surgical margins. RESULTS: A total of 11,173 patients underwent minimally invasive surgery for gastric adenocarcinoma between 2010 and 2019. Of those 8320 underwent LG and 2853 RG. Comparing the unmatched cohorts, RG was associated with a higher rate of adequate lymphadenectomy (63.5% vs 57.1%, p < .0.0001), higher rate of negative margins (93.8% vs 91.9%, p < 0.001), lower rate of prolonged length of stay (26.0% vs 29.6%, p < .0.001), lower 90-day mortality (3.7% vs 5.0%, p < 0.0001), and a better 5-year overall survival (OS) (56% vs 54%, p = 0.03). A propensity score-matching cohort with a 1:1 ratio was created utilizing the variables associated with lymphadenectomy ≥ 16 nodes. The matched analysis revealed that the rate of adequate lymphadenectomy was significantly higher for RG compared to LG, 63.5% vs 60.4% (p = 0.01), respectively. There was no longer a significant difference between RG and LG regarding the rate of negative margins, prolonged length of stay, 90-day mortality, rate of receipt of postoperative chemotherapy, and OS. CONCLUSIONS: This propensity score-matching analysis with a large US cohort shows that RG was associated with a higher rate of adequate lymphadenectomy compared to LR. RG and LG had a similar rate of negative margins, prolonged length of stay, receipt of postoperative chemotherapy, 90-day mortality, and OS, suggesting that RG is a comparable surgical approach, if not superior to LG.