Comments and Illustrations of Ultrasound Findings in Extrapulmonary Tuberculosis Manifestations.

This review describes the appearance of extrapulmonary tuberculosis manifestations in comprehensive and multiparametric ultrasound imaging. The aim is to increase awareness of typical ultrasound findings regarding extrapulmonary tuberculosis, correlate those with pathological features, and facilitate differential diagnosis. Point of care ultrasound protocols can be used as a screening method in high-risk populations, although the negative findings do not exclude tuberculosis. Conversely, the diagnosis of extrapulmonary tuberculosis can never be made using ultrasound alone, as many ultrasound findings in extrapulmonary tuberculosis are non-specific. However, ultrasound-based sampling techniques can significantly facilitate the collection of samples for microbiological or molecular proof of tuberculosis, as well as facilitating the establishment of alternative diagnoses.

Student ultrasound education - current views and controversies.

As an extension of the clinical examination and as a diagnostic and problem-solving tool, ultrasound has become an established technique for clinicians. A prerequisite for high-quality clinical ultrasound practice is adequate student ultrasound training. In light of the considerable heterogeneity of ultrasound curricula in medical studies worldwide, this review presents basic principles of modern medical student ultrasound education and advocates for the establishment of an ultrasound core curriculum embedded both horizontally and vertically in medical studies.

Echoscopy in scanning cardiac diseases in critical care medicine.

BACKGROUND AND AIMS: Targeted ultrasound examinations with a portable ultrasound device ("handheld ultrasound system"; HHUS) have been defined as "echoscopy" by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). Cardiac scanning with HHUS is feasible. Echoscopy could play a major role in emergency and intensive care medicine, but adequate data on its effectiveness are still lacking. Sonographic examinations in the field of emergency and intensive care medicine can often not be carried out under standardized examination conditions. Thus, the aim of this study is to show that the use of HHUS for echocardiography in emergency medicine is possible and that for this setting HHUS is not inferior to a high-end ultrasound system (HEUS) for detecting cardiac pathologies. METHODS: The examinations were carried out with a Vscan™ (GE Medical Systems, Solingen, Germany) and a high-end ultrasound device (Acuson X­300 or X­700). The examinations were randomized and blinded to two examiners within 30 min. The examinations took place in the intensive care unit, the emergency room and the ambulance service. The results were recorded in an examination sheet. RESULTS: In all, 93 patients (61 men and 32 women, age 69 ± 14.76 [33-95] years). In 32.6% (30/93) of examinations with HEUS the examination conditions were optimal and in 29.03% (27/93) when the HHUS was used. Of the examinations, 50.08% (31/61) were carried out by both examiners in the same patient position. Using HHUS, the following sensitivity and specificities (respectively) were found: pericardial effusion (73.68%; 96.97%), hemodynamically relevant effusion (50%; 97.67%), right heart strain (90,91%; 96,72%), arrest of the right ventricle (100%; 87,5%), limitation of left ventricular pump function (91.49%; 86.11%), wall movement disorders (WMD, 97.29%; 78.95%), aortic valve sclerosis (42.86%; 86.67%), aortic regurgitation (60%; 95%), mitral valve sclerosis (60%; 100%), mitral reguritation (66.67%; 82.86%), tricuspid valve regurgitation (48%; 81,48%). Measurements of the dimensions of pericardial effusion, the left ventricle, the left atrium and the left ventricular posterior wall each had a positive correlation between the examination with HHUS and HEUS (Κ = 0.45 to 0.91). The diameters determined by HHUS and HEUS for the septum and aortic root, however, correlated negatively (κ = -0.61 to -0.86). CONCLUSIONS: The use of echoscopy in emergency and intensive care medicine is not inferior to HEUS for detecting defined cardiac pathologies.

Echoscopy in scanning abdominal diseases in a critical care setting.

BACKGROUND AND AIMS: Targeted ultrasound examinations with portable ultrasound device (handheld ultrasound system [HHUS]) have been defined as "echoscopy" by the European Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB). For abdominal diseases it has been shown that echoscopy is sensitive and specific. The aim of this study is to show that the use of HHUS for abdominal ultrasonography is possible under the conditions prevailing in emergency and intensive care medicine and that it is not inferior to high-end devices (high-end ultrasound systems [HEUS]). METHODS: Examinations were carried out with a first-generation Vscan™ (GE Medical Systems, Solingen, Germany) and HEUS device (Siemens Acuson X­300 or X­700, Siemens Healthcare, Erlangen, Germany). The HEUS device was seen as standard. The examinations were randomized and blinded and carried out by two examiners within 30 min in order to avoid falsifications due to time delay. They took place in the intensive care unit, the emergency room and the emergency medical service. The results had to be recorded in an examination sheet. RESULTS: In all, 86 patients (54 men and 32 women, aged 73 ± 14.58 [28-95] years) were included. In 45.35% (39/86) of the ultrasound examinations using HEUS and in 41.86% (36/89) of the cases using HHUS the examination conditions were optimal. Furthermore, 76.19% of the examinations were carried out by both examiners in the same scanning position. For the detection of liver tumours, HHUS shows a sensitivity of 70% and specificity of 100%. With regard to identifying signs of cholecystitis, i.e., evidence of surrounding inflammation (a) or hydrops (b), HHUS shows a sensitivity of 66.67% (a) and 60% (b) and a specificity of 97.06% (a) and 96.86% (b). The diagnosis of an ileus is successful with a sensitivity of 87.5% and a specificity of 60%. The respiratory variability of the inferior vena cava has a sensitivity of 100% and a specificity of 40% using HHUS. Ascites and pleural effusions can be diagnosed with a sensitivity of 89% and a specificity of 93.1%. When using the FAST (Focused Assessment with Sonography for Trauma) protocol, HHUS has a sensitivity of 80% and a specificity of 90.9%. With the exception of kidney cysts and inferior vena cava, the measurement of the diameter has a positive correlation. CONCLUSION: Echoscopy of the abdomen in emergency and intensive care medicine is possible despite restrictive circumstances. The inferior vena cava can only be assessed to a limited extent with the first generation of Vscan™. In order to use sonography in emergency and intensive care medicine, a standardized procedure is to be aimed for and training in emergency sonography is necessary.

Early detection of pancreatic tumors by advanced EUS imaging.

The early detection of pancreatic ductal adenocarcinoma (PDAC) dramatically improves outcome. All available state-of-the-art imaging methods allow early detection with EUS being the best technique for exclusion of PDAC and detection of very early PDAC. Etiological differentiation of small SPL is important to guide individually tailored patients' management including radical surgery in resectable PDAC, medical (neoadjuvant or palliative intended) treatment in patients with non-resectable malignancy, pancreatic parenchyma saving strategies in some non-PDAC, and follow-up in particular in low-grade PanNEN or other small benign lesions. Multimodality EUS imaging including B-Mode assessment, elastography, contrast-enhancement and EUS-guided sampling is the most appropriate technique for diagnosis and risk assessment of small SPL. We present a review discussing modern (endoscopic) ultrasound imaging techniques including contrast enhanced ultrasound and elastography for the early detection and characterization of solid pancreatic lesions.

Conventional ultrasound for diagnosis of hepatic steatosis is better than believed.

BACKGROUND: Hepatic steatosis is a condition frequently encountered in clinical practice, with potential progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. Detection and staging of hepatic steatosis are of most importance in nonalcoholic fatty liver disease (NAFLD), a disease with a high prevalence of more than 1 billion individuals affected. Ultrasound (US) is one of the most used noninvasive imaging techniques used in the diagnosis of hepatic steatosis. Detection of hepatic steatosis with US relies on several conventional US parameters, which will be described. US is the first-choice imaging in adults at risk for hepatic steatosis. The use of some scoring systems may add additional accuracy especially in assessing the severity of hepatic steatosis. SUMMARY: In the presented paper, we discuss screening and risk stratification, ultrasound features for diagnosing hepatic steatosis, B-mode criteria, focal fatty patterns and Doppler features of the hepatic vessels, and the value of the different US signs for the diagnosis of liver steatosis including classifying the severity of steatosis using different US scores. Limitations of conventional B-mode and Doppler features in the evaluation of hepatic steatosis are also discussed, including those in grading and assessing the complications of steatosis, namely fibrosis and nonalcoholic steatohepatitis. KEY MESSAGES: Ultrasound is the first-line imaging examination for the screening and follow-up of patients with liver steatosis. The use of some scoring systems may add additional accuracy in assessing the severity of steatosis. Conventional B-mode and Doppler ultrasound have limitations in grading and assessing the complications of steatosis.

VueBox® for quantitative analysis of contrast-enhanced ultrasound in liver tumors1.

Dynamic contrast-enhanced ultrasound (DCE-US) enables quantification of tumor perfusion. VueBox is a platform independent external software using DICOM cine loops which objectively provides various DCE-US parameters of tumor vascularity. This review summaries its use for diagnosis and treatment monitoring of liver tumors. The existing literature provides evidence on the successful application of Vuebox based DCE-US for characterization and differential diagnosis of focal liver lesions, as well as on its use for monitoring of local ablative therapies and of modern systemic treatment in oncology.

"Knobology" in Doppler Ultrasound.

Ultrasonography is a ubiquitous and indispensable diagnostic and therapeutic tool in medicine. Due to modern equipment and automatic image optimization, nowadays the introduction of ultrasound imaging requires only little technical and physical knowledge. However, profound knowledge of the device function repertoire and underlying mechanisms are essential foroptimal image adjustment and documentation. From a medical as well as an aesthetic point of view, the goal should always be to achieve the best possible image quality. This article provides an overview of handling of ultrasound systems, fundamental adjustments and their optimization in Doppler ultrasound.

An International Consensus List of Potentially Clinically Significant Drug-Drug Interactions in Older People.

OBJECTIVES: We aimed to establish an explicit list of potentially clinically significant drug-drug interactions (DDIs) in people aged ≥65 years. DESIGN: A preliminary list of potentially clinically significant DDIs was compiled, based on 154 DDIs identified from literature review. Subsequently, a 2-round online Delphi survey was undertaken with a multidisciplinary expert panel. A consensus meeting and a final round were conducted to validate the final DDI list and the scope of information provided. SETTING AND PARTICIPANTS: Twenty nine experts, including geriatricians and clinical pharmacists from 8 European countries. MEASURES: For each DDI, in the first 2 rounds, experts were asked to score the severity of potential harm on a 5-point Likert-type scale. DDIs were directly included on the final list if the median score was 4 (major) or 5 (catastrophic). DDIs with a median score of 3 (moderate) were discussed at a consensus meeting and included if ≥75% of participants voted for inclusion in the final round. RESULTS: Consensus was achieved on 66 potentially clinically significant DDIs (28 had a median score of 4/5 and 48 of 3 in the Delphi survey). Most concerned cardiovascular, antithrombotic, and central nervous system drugs. The final list includes information on the mechanism of interaction, harm, and management. Treatment modification is recommended for three-quarters of DDIs. CONCLUSION AND IMPLICATIONS: We validated a list of potentially clinically significant DDIs in older people, which can be used in clinical practice and education to support identification and management of DDIs or to assess prevalence in epidemiologic and intervention studies.

General principles of image optimization in EUS.

With the development of modern EUS, multiple imaging functions, transducer settings, and examination modes have become available for clinical settings. While the major determinants of the ultrasound beam are still comprised of the signal wavelength, its frequency range, and its amplitude, other modifications and calculations have gained more interest for advanced users, such as tissue harmonic imaging (THI), spatial and frequency compounding, certain versions of speckle reduction, and various Doppler/duplex settings. The goal of such techniques is a better, perhaps more realistic image, with reduced artifacts (such as speckle), better image contrast, and an improved signal-to-noise ratio. In addition, "add-ons" such as THI, which is based on the phenomenon of nonlinear distortion of acoustic signals as they travel through tissues, provide greater contrast and an enhanced spatial resolution than conventional EUS. Finally, optimization of spectral and color Doppler imaging in EUS requires experience and knowledge about the basic principles of Doppler/duplex phenomena. For these purposes, factors such as adjustment of Doppler controls, Doppler angle, color gain, spectral wall filters, and others require special attention during EUS examinations. Incorporating these advanced techniques in EUS examinations may be time-consuming and cumbersome. Hence, practical guidelines enabling endosonographers to steer safely through the large quantity of technological properties and settings (knobology) are appreciated. This review provides an overview of the role of important imaging features to be adjusted before, during, and after EUS procedures.

What does liver elastography measure? Technical aspects and methodology.

Elastography can be thought as an extension of the ancient technique of palpation. After giving a short introduction to the history of elastography, the different technologies that are nowadays available and the physics behind them, the article focuses on the assessment of liver stiffness in patients with diffuse liver disease using shear wave elastography (SWE). Practical advices on how to perform the SWE techniques and on the factors that should be considered for a correct interpretation of the results are given. This paper aimed to provide a practical guide for beginners and advanced clinical users to better understand technical aspects, methodologies and terminology.

Ultrasound Image Optimization ("Knobology"): B-Mode.

Ultrasound is a ubiquitous and indispensable diagnostic and therapeutic tool in medicine. Due to modern equipment and automatic image optimization, the introduction of ultrasound imaging currently requires only little technical and physical knowledge. However, in-depth knowledge of the device functions and underlying mechanisms is essential for optimal image adjustment and documentation. From a medical as well as an aesthetic point of view, the goal should always be to achieve the best possible image quality. The first part of this article provides an overview of the handling of ultrasound systems, fundamental adjustments, and their optimization in B-mode ultrasound.

Intervention protocol: OPtimising thERapy to prevent avoidable hospital Admission in the Multi-morbid elderly (OPERAM): a structured medication review with support of a computerised decision support system.

BACKGROUND: Several approaches to medication optimisation by identifying drug-related problems in older people have been described. Although some interventions have shown reductions in drug-related problems (DRPs), evidence supporting the effectiveness of medication reviews on clinical and economic outcomes is lacking. Application of the STOPP/START (version 2) explicit screening tool for inappropriate prescribing has decreased inappropriate prescribing and significantly reduced adverse drug reactions (ADRs) and associated healthcare costs in older patients with multi-morbidity and polypharmacy. Therefore, application of STOPP/START criteria during a medication review is likely to be beneficial. Incorporation of explicit screening tools into clinical decision support systems (CDSS) has gained traction as a means to improve both quality and efficiency in the rather time-consuming medication review process. Although CDSS can generate more potential inappropriate medication recommendations, some of these have been shown to be less clinically relevant, resulting in alert fatigue. Moreover, explicit tools such as STOPP/START do not cover all relevant DRPs on an individual patient level. The OPERAM study aims to assess the impact of a structured drug review on the quality of pharmacotherapy in older people with multi-morbidity and polypharmacy. The aim of this paper is to describe the structured, multi-component intervention of the OPERAM trial and compare it with the approach in the comparator arm. METHOD: This paper describes a multi-component intervention, integrating interventions that have demonstrated effectiveness in defining DRPs. The intervention involves a structured history-taking of medication (SHiM), a medication review according to the systemic tool to reduce inappropriate prescribing (STRIP) method, assisted by a clinical decision support system (STRIP Assistant, STRIPA) with integrated STOPP/START criteria (version 2), followed by shared decision-making with both patient and attending physician. The developed method integrates patient input, patient data, involvement from other healthcare professionals and CDSS-assistance into one structured intervention. DISCUSSION: The clinical and economical effectiveness of this experimental intervention will be evaluated in a cohort of hospitalised, older patients with multi-morbidity and polypharmacy in the multicentre, randomized controlled OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multi-morbid elderly), which will be completed in the last quarter of 2019. TRIAL REGISTRATION: Universal Trial Number: U1111-1181-9400 Clinicaltrials.gov: NCT02986425, Registered 08 December 2016. FOPH (Swiss national portal): SNCTP000002183. Netherlands Trial Register: NTR6012 (07-10-2016).

Skeletal Effects of Levothyroxine for Subclinical Hypothyroidism in Older Adults: A TRUST Randomized Trial Nested Study.

CONTEXT: Both thyroid dysfunction and levothyroxine (LT4) therapy have been associated with bone loss, but studies on the effect of LT4 for subclinical hypothyroidism (SHypo) on bone yielded conflicting results. OBJECTIVE: To assess the effect of LT4 treatment on bone mineral density (BMD), Trabecular Bone Score (TBS), and bone turnover markers (BTMs) in older adults with SHypo. DESIGN AND INTERVENTION: Planned nested substudy of the double-blind placebo-controlled TRUST trial. Participants with SHypo were randomized to LT4 with dose titration versus placebo with computerized mock titration. SETTING AND PARTICIPANTS: 196 community-dwelling adults over 65 years enrolled at the Swiss TRUST sites had baseline and 1-year follow-up bone examinations; 4 participants withdrew due to adverse events not related to treatment. MAIN OUTCOME MEASURES: One-year percentage changes of BMD, TBS, and 2 serum BTMs (serum CTX-1 [sCTX] and procollagen type 1 N-terminal polypeptide [P1NP]). Student's t-test for unadjusted analyses and linear regression adjusted for clinical center and sex were performed. RESULTS: Mean age was 74.3 years ± 5.7, 45.4% were women, and 19.6% were osteoporotic. The unadjusted 1-year change in lumbar spine BMD was similar between LT4 (+0.8%) and placebo-treated groups (-0.6%; between-groups difference +1.4%: 95% confidence interval [CI] -0.1 to 2.9, P = .059). Likewise, there were no between-group differences in 1-year change in TBS (-1.3%: 95% CI -3.1 to 0.6, P = .19), total hip BMD (-0.2%: 95% CI -1.1 to 0.1, P = .61), or BTMs levels (sCTX +24.1%: 95% CI -7.9 to 56.2, P = .14), or after adjustment for clinical centers and sex. CONCLUSIONS: Over 1-year levothyroxine had no effect on bone health in older adults with SHypo. REGISTRATION: ClinicalTrial.gov NCT01660126 and NCT02491008.

'Optimising PharmacoTherapy In the multimorbid elderly in primary CAre' (OPTICA) to improve medication appropriateness: study protocol of a cluster randomised controlled trial.

INTRODUCTION: Multimorbidity and polypharmacy are major risk factors for potentially inappropriate prescribing (eg, overprescribing and underprescribing), and systematic medication reviews are complex and time consuming. In this trial, the investigators aim to determine if a systematic software-based medication review improves medication appropriateness more than standard care in older, multimorbid patients with polypharmacy. METHODS AND ANALYSIS: Optimising PharmacoTherapy In the multimorbid elderly in primary CAre is a cluster randomised controlled trial that will include outpatients from the Swiss primary care setting, aged ≥65 years with ≥three chronic medical conditions and concurrent use of ≥five chronic medications. Patients treated by the same general practitioner (GP) constitute a cluster, and clusters are randomised 1:1 to either a standard care sham intervention, in which the GP discusses with the patient if the medication list is complete, or a systematic medication review intervention based on the use of the 'Systematic Tool to Reduce Inappropriate Prescribing'-Assistant (STRIPA). STRIPA is a web-based clinical decision support system that helps customise medication reviews. It is based on the validated 'Screening Tool of Older Person's Prescriptions' (STOPP) and 'Screening Tool to Alert doctors to Right Treatment' (START) criteria to detect potentially inappropriate prescribing. The trial's follow-up period is 12 months. Outcomes will be assessed at baseline, 6 and 12 months. The primary endpoint is medication appropriateness, as measured jointly by the change in the Medication Appropriateness Index (MAI) and Assessment of Underutilisation (AOU). Secondary endpoints include the degree of polypharmacy, overprescribing and underprescribing, the number of falls and fractures, quality of life, the amount of formal and informal care received by patients, survival, patients' quality adjusted life years, patients' medical costs, cost-effectiveness of the intervention, percentage of recommendations accepted by GPs, percentage of recommendation rejected by GPs and patients' willingness to have medications deprescribed. ETHICS AND DISSEMINATION: The ethics committee of the canton of Bern in Switzerland approved the trial protocol. The results of this trial will be published in a peer-reviewed journal. MAIN FUNDING: Swiss National Science Foundation, National Research Programme (NRP 74) 'Smarter Healthcare'. TRIAL REGISTRATION NUMBERS: Clinicaltrials.gov (NCT03724539), KOFAM (Swiss national portal) (SNCTP000003060), Universal Trial Number (U1111-1226-8013).

Prognostic Value of Electrocardiography in Elderly Patients with Acute Pulmonary Embolism.

BACKGROUND: Electrocardiographic (ECG) signs of right ventricular strain could be used as a simple tool to risk-stratify patients with acute pulmonary embolism. METHODS: We studied consecutive patients aged ≥65 years with acute pulmonary embolism in a prospective multicenter cohort study. Two readers independently analyzed 12 predefined ECG signs of right ventricular strain in all patients. The outcome was the occurrence of an adverse clinical event, defined as death from any cause within 90 days or a complicated in-hospital course. We determined the interrater reliability for each ECG sign and examined the association between right ventricular strain signs and adverse events using logistic regression, adjusting for the Pulmonary Embolism Severity Index and cardiac troponin. RESULTS: Overall, 320/390 patients (82%) showed at least one ECG sign of right ventricular strain. The interrater reliability for individual ECG signs was highly variable (ᴋ 0.40-0.95). Patients with ≥1 of the 3 classic signs of right ventricular strain (S1Q3T3, right bundle branch block, or T wave inversions in V1-V4) had a higher incidence of adverse events than those without (13% vs 6%; P = .026). After adjustment, the presence of ≥1 of the 3 classic signs of right ventricular strain (odds ratio 2.11; 95% confidence interval, 1.00-4.46) and the number of right ventricular strain signs present were significantly associated with adverse events (odds ratio 1.35 per sign; 95% confidence interval, 1.08-1.69). CONCLUSIONS: ECG signs of right ventricular strain are common in elderly patients with acute pulmonary embolism. Although such signs may have prognostic value, their variable reliability and the rather modest prognostic effect size may limit their usefulness in the risk stratification of pulmonary embolism.

Agents that activate the High Osmolarity Glycerol pathway as a means to combat pathogenic molds.

Treatment of invasive fungal infections often fails due to the limited number of therapeutic options. In this study, we have analyzed the impact of agents activating the High Osmolarity Glycerol (HOG) pathway on molds that cause infections in humans and livestock. We found that agents like fludioxonil and iprodione, have a clear anti-fungal activity against pathogenic Aspergillus, Lichtheimia, Rhizopus and Scedosporium species. Only A. terreus turned out to be resistant to fludioxonil, even though it is sensitive to iprodione and able to adapt to hyperosmotic conditions. Moreover, the A. terreus tcsC gene can fully complement an A. fumigatus ΔtcsC mutant, thereby also restoring its sensitivity to fludioxonil. The particular phenotype of A. terreus is therefore likely to be independent of its TcsC kinase. In a second part of this study, we further explored the impact of fludioxonil using A. fumigatus as a model organism. When applied in concentrations of 1-2µg/ml, fludioxonil causes an immediate growth arrest and, after longer exposure, a quantitative killing. Hyphae respond to fludioxonil by the formation of new septa and closure of nearly all septal pores. Mitosis occurs in all compartments and is accompanied by a re-localization of the NimA kinase to the cytoplasm. In the swollen compartments, the massive extension of the cell wall triggers a substantial reorganization resulting in an enhanced incorporation of chitin and, most strikingly, a massive loss of galactomannan. Hence, HOG-activating agents have dramatic cell biological consequences and may represent a valuable, future element in the armory that can be used to combat mold infections.