Assessment of Basic Thoracic Ultrasound Skills in Immersive Virtual Reality: Gathering Validity Evidence.

OBJECTIVE: Operator skills are essential for thoracic ultrasound (TUS) to ensure diagnostic accuracy. Immersive virtual reality (IVR) has shown potential within medical education but never for assessment of TUS skills. This study was aimed at developing an IVR test for assessing TUS skills, gathering validity evidence and establishing a pass/fail score. METHODS: An expert panel developed a test based on the TUS protocol by the European Respiratory Society (ERS), including a tutorial and two clinical cases (pleural effusion and interstitial syndrome), using an IVR platform (VitaSim, Odense, Denmark). Four anterior, four lateral and six posterior zones were available for examination and decision of diagnosis. Each correct examination equaled one point. The contrasting groups' method was used to set a pass/fail score. RESULTS: Data were collected during the 2022 ERS Congress. We included 13 novices (N, experience: 0 TUS), 22 intermediates (I, 1-50 TUS) and 11 experienced clinicians (E, >50 TUS). Cronbach's α was 0.86. The total mean point scores in case 1 (C1) were (N) 5.0 ± 2.7, (I) 7.3 ± 2.4 and (E) 8.7 ± 1.3, and the scores in case 2 (C2) were (N) 4.5 ± 1.8, (I) 6.7 ± 2.3 and (E) 8.5 ± 2.1. Significant differences were found between N and I for C1 (p = 0.007) and C2 (p = 0.02), I and E for C1 (p = 0.04) and C2 (p = 0.019) and N and E for C1 (p < 0.001) and C2 (p < 0.001). The pass/fail score was 7 points in each case. CONCLUSION: We established an IVR test that can distinguish between operators with different TUS skills. This enables a standardized, objective and evidence-based approach to assessment of TUS skills.

The legacy of terrestrial plant evolution on cell wall fine structure.

The evolution of land flora was an epochal event in the history of planet Earth. The success of plants, and especially flowering plants, in colonizing all but the most hostile environments required multiple mechanisms of adaptation. The mainly polysaccharide-based cell walls of flowering plants, which are indispensable for water transport and structural support, are one of the most important adaptations to life on land. Thus, development of vasculature is regarded as a seminal event in cell wall evolution, but the impact of further refinements and diversification of cell wall compositions and architectures on radiation of flowering plant families is less well understood. We approached this from a glyco-profiling perspective and, using carbohydrate microarrays and monoclonal antibodies, studied the cell walls of 287 plant species selected to represent important evolutionary dichotomies and adaptation to a variety of habitats. The results support the conclusion that radiation of flowering plant families was indeed accompanied by changes in cell wall fine structure and that these changes can obscure earlier evolutionary events. Convergent cell wall adaptations identified by our analyses do not appear to be associated with plants with similar lifestyles but that are taxonomically distantly related. We conclude that cell wall structure is linked to phylogeny more strongly than to habitat or lifestyle and propose that there are many approaches of adaptation to any given ecological niche.

Persistently Decreased Quality of Life and its Determinants in Previous Illicit Androgen Users.

BACKGROUND AND OBJECTIVES: Quality of life (QoL) has never been assessed in previous illicit users of androgens years following androgen cessation. Therefore, the objective of this study was to assess QoL in previous illicit androgen users compared with current illicit androgen users and controls who had never used androgens. METHODS: Cross-sectional study including men involved in recreational strength training grouped according to their history of androgen use. We used the RAND Short-Form-36 questionnaire to assess physical and mental health-related QoL. RESULTS: We included 77 previous and 118 current androgen users and 39 healthy nonusers. The mean (SD) age of all participants was 33 (8) years. The elapsed duration since androgen cessation, geometric mean (95% CI), was 2.0 (1.5-2.6) years in former users. Median (25th-75th percentiles) serum total testosterone was lower in former users than controls, 14 (11-17) vs 19 (16-21) nmol/L, P < .001. Previous users displayed lower mean (SD) across both mental and physical (PCS) component summary scores, 48 (10) vs 54 (4) (P = .004) and 48 (9) vs 53 (3) (P = .002) compared with controls.Using multivariate linear regressions, evaluating physical and mental component scores as dependent variables, lower serum total testosterone, longer duration since androgen cessation, study recruitment from an endocrine outpatient clinic, and established chronic diseases were all independently associated with reduced QoL in previous users, P < .05. CONCLUSIONS: Previous illicit androgen users exhibited reduced QoL 2 years after androgen discontinuation, which may be a persistent condition.

The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. METHODS: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. RESULTS: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. CONCLUSIONS: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Thoracic ultrasonographic and clinical findings at 12-month follow-up of patients admitted with COVID-19.

Introduction: Thoracic ultrasound (TUS) has proven useful in the diagnosis, risk stratification and monitoring of disease progression in patients with coronavirus disease 2019 (COVID-19). However, utility in follow-up is poorly described. To elucidate this area, we performed TUS as part of a 12-month clinical follow-up in patients previously admitted with COVID-19 and correlated findings with clinical assessment and pulmonary function tests. Methods: Adult patients discharged from our hospital following admission with COVID-19 during March to May 2020 were invited to a 12-month follow-up. Enrolled patients were interviewed regarding persisting or newly developed symptoms in addition to TUS, spirometry and a 6-min walk test. Patients were referred to high-resolution computed tomography (HRCT) of the lungs if suspicion of pulmonary fibrosis was raised. Results: Forty patients were enrolled in the study of whom had 13 developed acute respiratory distress syndrome (ARDS) during admission. Patients with ARDS were more prone to experience neurological symptoms at follow-up (p = 0.03) and showed more B-lines on TUS (p = 0.008) but did not otherwise differ significantly in terms of pulmonary function tests. Four patients had pathological findings on TUS where subsequent diagnostics revealed that two had interstitial lung abnormalities and two had heart failure. These four patients presented with a significantly lower diffusing capacity of lung for carbon monoxide (p=0.03) and 6-min walking distance (p=0.006) compared to the remaining 36 patients without ultrasound pathology. No significant difference was observed in spirometry values of % of predicted FEV1 (p=0.49) or FVC (p=0.07). No persisting cardiovascular pathology was observed in patients without ultrasonographic pathology. Conclusion: At 12-month after admission with COVID-19, a follow-up combining TUS, clinical assessment, and pulmonary function tests may improve the selection of patients requiring further diagnostic investigations such as HRCT or echocardiography.

The effects of empagliflozin on measured glomerular filtration rate and estimated extracellular and plasma volumes in patients with type 2 diabetes.

AIMS: To investigate the effects of empagliflozin on measured glomerular filtration rate (mGFR), estimated plasma volume (PV) and estimated extracellular volume (ECV) in a cohort of patients with type 2 diabetes (T2D) and high risk of cardiovascular events. MATERIALS AND METHODS: In this prespecified substudy of the randomized, placebo-controlled SIMPLE trial, patients with T2D at high risk of cardiovascular events were allocated to either empagliflozin 25 mg or placebo once daily for 13 weeks. The prespecified outcome was between-group change in mGFR, measured by the 51 Cr-EDTA method after 13 weeks; changes in estimated PV and estimated ECV were included. RESULTS: From April 4, 2017 to May 11, 2020, 91 participants were randomized. Of these, 45 patients from the empagliflozin group and 45 patients from the placebo group were included in the intention-to-treat analysis. Treatment with empagliflozin reduced mGFR by -7.9 mL/min (95% confidence interval [CI] -11.1 to -4.7; P < 0.001), estimated ECV by -192.5 mL (95% CI -318.0 to -66.9; P = 0.003) and estimated PV by -128.9 mL (95% CI -218.0 to 39.8; P = 0.005) at Week 13. CONCLUSIONS: Treatment with empagliflozin for 13 weeks reduced mGFR, estimated ECV and estimated PV in patients with T2D and high risk of cardiovascular events.

Higher Myonuclei Density in Muscle Fibers Persists Among Former Users of Anabolic Androgenic Steroids.

CONTEXT: No information exists on the long-lasting effects of supraphysiological anabolic androgenic steroids (AASs) usage on the myocellular properties of human skeletal muscle in previous AAS users. OBJECTIVE: We hypothesized that former AAS users would demonstrate smaller myonuclei domains (ie, higher myonuclei density) than matched controls. METHODS: A community-based cross-sectional study in men aged 18-50 years engaged in recreational strength training. Muscle biopsies were obtained from the m. vastus lateralis. Immunofluorescence analyses were performed to quantify myonuclei density and myofiber size. RESULTS: Twenty-five males were included: 8 current and 7 previous AAS users and 10 controls. Median (25th-75th percentiles) accumulated duration of AAS use was 174 (101-206) and 140 (24-260) weeks in current and former AAS users, respectively (P = .482). Geometric mean (95% CI) elapsed duration since AAS cessation was 4.0 (1.2; 12.7) years among former AAS users. Type II muscle fibers in former AAS users displayed higher myonuclei density and DNA to cytoplasm ratio than controls, corresponding to smaller myonuclei domains (P = .013). Longer accumulated AAS use (weeks, log2) was associated with smaller myonuclei domains in previous AAS users: beta-coefficient (95% CI) -94 (-169; -18), P = .024. Type I fibers in current AAS users exhibited a higher amount of satellite cells per myofiber (P = .031) than controls. CONCLUSION: Muscle fibers in former AAS users demonstrated persistently higher myonuclei density and DNA to cytoplasm ratio 4 years after AAS cessation suggestive of enhanced retraining capacity.

Effect on cardiac function among patients with type 2 diabetes following high-dose mineralocorticoid receptor antagonist using echocardiography; data from the MIRAD randomized clinical trial.

BACKGROUND: Early heart failure prevention is central in patients with type 2 diabetes, and mineralocorticoid receptor antagonists (MRAs) have shown to improve prognosis. We investigated the effect of high-dose MRA, eplerenone, on cardiac function and structure in patients with type 2 diabetes and established or increased risk of cardiovascular disease but without heart failure. METHODS: In the current randomized, placebo-controlled clinical trial, 140 patients with high-risk type 2 diabetes were randomized to high-dose eplerenone (100-200 mg daily) or placebo as add-on to standard care for 26 weeks. Left ventricular systolic and diastolic function, indexed left ventricular mass (LVMi), and global longitudinal strain (GLS) were assessed using echocardiography at baseline and after 26 weeks of treatment. RESULTS: Of the included patients, 138 (99%) had an echocardiography performed at least once. Baseline early diastolic in-flow velocity (E-wave) indexed by mitral annulus velocity (e') was mean (SD) 11.1 (0.5), with 31% of patients reaching above 12. No effect of treatment on diastolic function was observed measured by E/e' (0.0, 95%CI [-1.2 to 1.2], P = 0.992) or E/A (-0.1, 95%CI [-0.2 to 0.0], P = 0.191). Mean left ventricular ejection fraction (LVEF) at baseline was 59.0% (8.0). No improvement in systolic function was observed when comparing groups after 26 weeks (LVEF: 0.9, 95%CI [-1.1 to 2.8], P = 0.382; GLS: -0.4%, 95%CI [-1.5 to 0.6], P = 0.422), nor in LVMi (-3.8 g/m2 95%CI [-10.2 to 2.7], P = 0.246). CONCLUSION: In the present echo sub-study, no change in left ventricular function was observed following high-dose MRA therapy in patients with type 2 diabetes when evaluated by conventional echocardiography. TRIAL REGISTRATION: Date of registration 25/08/2015 (EudraCT number: 2015-002,519-14).

Multiorgan ultrasonographic findings in patients with pulmonary embolism at diagnosis and clinical follow-up: a proof of concept study.

PURPOSE: The purpose of this descriptive feasibility study was to assess the clinical impact and feasibility of conducting a multiorgan ultrasound examination of patients with pulmonary embolism at both time of diagnosis and at clinical follow-up. METHODS: Hemodynamically stable patients with pulmonary embolism verified by CT pulmonary angiography or ventilation perfusion scintigraphy were eligible for inclusion. Enrolled patients underwent multiorgan ultrasound investigation encompassing echocardiography supplemented with focused lung and deep venous ultrasound emphasizing right ventricular strain, subpleural consolidations and presence of deep venous thrombi. Identical investigations were conducted at 3 months follow-up. The presence of ultrasonographic findings at diagnosis and follow-up was compared and the clinical impact of any remaining pathology or strain was described. RESULTS: Twenty-one patients were enrolled in the study of whom 20 survived to attend follow-up. Mean age was 62 ± 15 years and 48% were female. At diagnosis, the most prevalent ultrasonographic findings were subpleural consolidations in 11 patients and right ventricular dilation in eight. At follow-up, signs of right ventricular strain had resolved in all patients. However, in one patient, no resolution was seen in a subpleural consolidation observed at the time of pulmonary embolism diagnosis, resulting in referral to a chest CT. Additionally, one patient exhibited residual deep venous thrombotic material, leading to prolongation of anticoagulative treatment. CONCLUSION: In patients with pulmonary embolism, multiorgan ultrasound is feasible in follow-up and adequately powered studies should determine the clinical utility of such an approach.

Education in Focused Lung Ultrasound Using Gamified Immersive Virtual Reality: A Randomized Controlled Study.

Focused lung ultrasound (FLUS) has high diagnostic accuracy in many common conditions seen in a variety of emergency settings. Competencies are essential for diagnostic success and patient safety but can be challenging to acquire in clinical environments. Immersive virtual reality (IVR) offers an interactive risk-free learning environment and is progressing as an educational tool. First, this study explored the educational impact of novice FLUS users participating in a gamified or non-gamified IVR training module in FLUS by comparing test scores using a test with proven validity evidence. Second, the learning effect was assessed by comparing scores of each group with known test scores of novices, intermediates and experienced users in FLUS. A total of 48 participants were included: 24 received gamified and 24 received non-gamified IVR training. No significant difference was found between gamified (mean = 15.5 points) and non-gamified (mean = 15.2 points), indicating that chosen gamification elements for our setup did not affect learning outcome (p = 0.66). The mean scores of both groups did not significantly differ from those of known intermediate users in FLUS (gamified p = 0.63, non-gamified p = 0.24), indicating that both IVR modules could be used as unsupervised out-of-hospital training for novice trainees in FLUS.

Reduction of cardiac adipose tissue volume with short-term empagliflozin treatment in patients with type 2 diabetes: A substudy from the SIMPLE randomized clinical trial.

OBJECTIVE: Ectopic accumulation of cardiac adipose tissue volume (CAT) has been associated with cardiac remodelling and cardiac dysfunction in type 2 diabetes and may be a future therapeutic target. In this substudy from the SIMPLE-trial, we investigated short-term empagliflozin therapy's effects on CAT in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Between 4 April 2017 and 11 May 2020, we randomized 90 patients with type 2 diabetes and established or high risk of cardiovascular disease to 25 mg empagliflozin or placebo for 13 weeks. The substudy focused on change in CAT evaluated by images acquired during 82 Rubidium-positron emissions tomography/computed tomography. The analysis included 78 patients who had at least one scan. Furthermore, we report on the relation to the concurrent effects on left ventricular mass, end-diastolic volume and end-systolic volume, body composition and glucometabolic status. RESULTS: Mean ± SD baseline CAT was 258.5 ± 117.9 ml. Empagliflozin reduced CAT after 13 weeks by 12.41 ml [95% CI (-23.83 to -0.99), p = .034] as compared with placebo. Similarly, left ventricular mass [-5.16 g, 95% CI (-8.80 to -1.52), p = .006], end-diastolic volume and end-systolic volume decreased with empagliflozin. In addition, significant improvements were observed in body composition, with reduced total fat mass, and in measures of glucose and lipid metabolism. However, no correlation was observed between changes in CAT and changes in cardiac parameters and change in CAT appeared mediated primarily by concurrent change in weight. CONCLUSIONS: Empagliflozin provides an early reduction of CAT; however, no association was observed with concurrent changes in cardiac volumetrics.

Immersive Virtual Reality in Basic Point-of-Care Ultrasound Training: A Randomized Controlled Trial.

This study was aimed at comparing the learning efficacy of a traditional instructor-led lesson with that of a completely virtual, self-directed lesson in immersive virtual reality (IVR) in teaching basic point-of-care ultrasound (PoCUS) skills. We conducted a blinded, non-inferiority, parallel-group, randomized controlled trial in which final-year medical students were randomized to an instructor-led (n = 53) or IVR (n = 51) lesson. Participants' learning efficacy was evaluated by blinded assessors, who rated each participant's performance using the Objective Structured Assessment of Ultrasound Skills (OSAUS) assessment tool.The mean total scores for participants were 11.0 points (95% confidence interval: 9.8-12.2) for the instructor-led lesson and 10.3 points (95% confidence interval: 9.0-11.5) for the IVR lesson. No significant differences were observed between the groups with respect to total score (p = 0.36) or subgroup objectives of the OSAUS score (p = 0.34 for familiarity, p = 0.45 for image optimization, p = 0.96 for systematic approach and p = 0.07 for interpretation). Maintenance costs for both courses were estimated at 400 euros each. Startup costs for the instructor-led course were estimated 16 times higher than those for the IVR course. The learning efficacy of an instructor-led lesson on basic US did not differ significantly from that of a self-directed lesson in IVR, as assessed using the OSAUS. The results suggest that IVR could be an equivalent alternative to instructor-led lessons in future basic US courses, but further research is warranted to clarify the role of IVR in PoCUS courses.

Higher recipient pre-transplant FOXP3 mRNA expression is associated with acute leukaemia relapse after HSCT.

The effect of higher FOXP3 mRNA expression by recipient pre-transplant CD4+ T cells on leukaemia relapse was analysed in a series of 106 patients who received allogeneic haematopoietic stem cell transplantation after myeloablative conditioning with or without antithymocyte globulin (ATG) due to acute leukaemia in 1st or 2nd complete remission. FOXP3 mRNA was measured by qPCR in purified CD4+ T cells from blood obtained before conditioning. Higher FOXP3 mRNA expression was associated with an increased relapse risk when conditioning included ATG (n = 43, hazard ratio [HR] 11.0 [2.50-48.4], p = 0.00001). No effect was observed in patients not receiving ATG (HR 0.95 [0.53-1.81]).

Does the Addition of Radial Endobronchial Ultrasound Improve the Diagnostic Yield of Electromagnetic Navigation Bronchoscopy? A Systematic Review.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Early diagnosis is crucial to increased survival rates. Radial endobronchial ultrasound (rEBUS) and electromagnetic navigation bronchoscopy (ENB) have been developed for the diagnosis of small lung lesions. The aim of this systematic review was to evaluate whether the combination of rEBUS and ENB is superior to ENB alone. METHOD: A systematic search was performed using MEDLINE, Embase, and Cochrane Library databases on "ENB," and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The project was registered with PROSPERO, number CRD42020214682. RESULTS: In total, 2,092 studies were identified through a literature search. Five studies were included in the final review. One study found that the addition of rEBUS increased diagnostic yield, while another concluded the converse. Three studies did not have significant results. Meta-analysis was not feasible due to heterogeneity and the small number of studies. CONCLUSION: As the current evidence on the topic is sparse and heterogeneous, it is not possible to conclude whether the addition of rEBUS to ENB has a significant impact on diagnostic yield. Further studies are needed to illuminate this question in order to ensure optimal choice of endoscopic technique as well as used time and resources. The project received funding from the Region of Southern Denmark's PhD fund.

Using Immersive Virtual Reality Simulation to Ensure Competence in Contrast-Enhanced Ultrasound.

Contrast-enhanced ultrasound (CEUS) is used in various medical specialties as a diagnostic imaging tool and for procedural guidance. Experience in the procedure is currently attained via supervised clinical practice that is challenged by patient availability and risks. Prior simulation-based training and subsequent assessment could improve and ensure competence before performance on patients, but no simulator currently exists. Immersive virtual reality (IVR) is a new promising simulation tool that can replicate complex interactions and environments that are unfeasible to achieve by traditional simulators. This study was aimed at developing an IVR simulation-based test for core CEUS competencies and gathering validity evidence for the test in accordance with Messick's framework. The test was developed by IVR software specialists and clinical experts in CEUS and medical education and imitated a CEUS examination of a patient with a focal liver lesion with emphasis on the pre-contrast preparations. Twenty-five medical doctors with varying CEUS experience were recruited as test participants, and their results were used to analyze test quality and to establish a pass/fail standard. The final test of 23 test items had good internal reliability (Cronbach's α = 0.85) and discriminatory abilities. The risks of false positives and negatives (9.1% and 23.6%, respectively) were acceptable for the test to be used as a certification tool prior to supervised clinical training in CEUS.

Cavitating pulmonary lung lesions with more than one microbiological aetiology.

Non-tuberculous mycobacteria (NTM) are one of the predominant microbes observed in immunocompromised patients with structural lung disease. Especially in immunocompromised patients, the treating physician needs to be aware of concurrent lung infections with opportunistic pathogens. In this case report we present a man in his 60s with severe chronic obstructive pulmonary disease (COPD) and bullous emphysema, who was diagnosed with Mycobacterium europaeum but with persistent clinical deterioration despite relevant treatment for NTM. A subsequent bronchoalveolar lavage (BAL) revealed elevated Aspergillus galactomannan antigen which, when seen in relation to imaging-findings of cavitating opacities with aggravating surrounding consolidation, raised suspicion of concurrent subacute invasive aspergillosis. Antifungal treatment was initiated but due to intolerable side effects was discontinued after only a few weeks. This case highlights the importance of concurrent testing for pulmonary aspergillosis in NTM patients and vice versa before treatment initiation and if the disease and symptoms are progressing despite relevant treatment.

WFUMB Technological Review: How to Perform Contrast-Enhanced Ultrasound of the Lung.

The use of ultrasound has revolutionized the evaluation of pulmonary complaints and pathology. Historically, most lung ultrasound uses described are limited to B-mode, M-mode and occasionally color Doppler. However, the use of contrast can significantly expand the diagnostic capabilities of lung ultrasound. Ultrasound contrast enables significant expansion of therapeutic and intervention capabilities. We provide a detailed description of contrast administration, phases and uses in lung ultrasound. Additionally provided are example contrast use cases and illustrative examples of contrast use in a wide range of lung ultrasound applications including pneumonia, atelectasis, pulmonary embolism and neoplasms. Clinical practice examples will help providers incorporate contrast use into their lung ultrasound practice.

Monitoring patients with acute dyspnea with serial point-of-care ultrasound of the inferior vena cava (IVC) and the lungs (LUS): a systematic review.

PURPOSE: The primary aim was to investigate if treatment guided by serial ultrasound of the inferior vena cava-collapsibility index (IVC-CI) and B-lines on lung ultrasound (LUS) could reduce mortality, readmissions, and length of stay (LOS) in acutely dyspneic patients admitted to a hospital, compared to standard monitoring. The secondary aim was to determine how the changes of B-lines and IVC-CI are correlated to vitals and symptoms. METHODS: A systematic search was conducted on PubMed, Embase, Cochrane, Google Scholar, Web of Science, Scopus, OpenGrey, ProQuest, and databases for ongoing trials. The risk of bias was assessed according to study design. RESULTS: Of the 8258 studies identified, 50 were selected for full-text screening, and 24 studies were chosen for data extraction (19 pre-post-, two non-randomized controlled-, two randomized controlled-, and one retrospective cohort study), covering 2040 patients. Most studies were single-center and had small study populations with only heart failure patients. The risk of bias was high. No studies evaluated how the difference between two ultrasound measurements correlated with the primary outcomes. Seven studies reported that a decline in either B-lines or IVC size, or an increased IVC-CI reduced mortality, readmissions, and LOS when correlated to a single ultrasound measurement. All studies showed changes in the IVC-CI and B-lines, but these were not related to vitals or symptoms. CONCLUSION: B-lines and IVC-CI are dynamic variables that change over time and with treatment. A single ultrasound measurement can influence prognostic outcomes, but it remains uncertain if repeated scans can have the same impact.

Clinical Applications of Contrast-Enhanced Thoracic Ultrasound (CETUS) Compared to Standard Reference Tests: A Systematic Review.

INTRODUCTION: Contrast-enhanced ultrasound is utilized in an increasing array of medical fields, including thoracic medicine. However, the technique is still relatively new and only sporadically mentioned in current guidelines and recommendations. The aim of this systematic review is to provide a literature overview and to critically appraise the current clinical applications of contrast-enhanced thoracic ultrasound (CETUS). MATERIALS AND METHODS: A systematic literature search using major electronic databases and in accordance with PRISMA guidelines was performed. Studies with a primary focus on CETUS of thoracic disorders compared to a standard reference test were included. The QUADAS-2 tool was used for quality assessment of the studies. RESULTS: The search identified 43 articles: 1 randomized controlled study, 6 non-randomized controlled studies, 16 non-randomized non-controlled studies, 5 case series, 10 single case reports, and 5 animal studies. The overall risk of bias was judged to be high. Diagnostic accuracy measurements of noninvasive applications of CETUS were only reported in a few studies and they were too dissimilar for meta-analysis. Six studies compared CETUS-guided versus ultrasound-guided transthoracic needle biopsy of thoracic masses. They individually reported a significant increase in diagnostic accuracy in favor of CETUS guidance but were too heterogeneous for meta-analysis. CONCLUSION: The current literature on CETUS is overall heterogeneous with a few high evidence level studies, small study populations and a high risk of bias. CETUS-guided biopsy is the most frequent clinical application and increases diagnostic accuracy compared to ultrasound guidance by an average of 14.6 percentage points.