Postmortem Minimally Invasive Autopsy in Critically Ill COVID-19 Patients at the Bedside: A Proof-of-Concept Study at the ICU.

BACKGROUND: Economic restrictions and workforce cuts have continually challenged conventional autopsies. Recently, the COVID-19 pandemic has added tissue quality and safety requirements to the investigation of this disease, thereby launching efforts to upgrade autopsy strategies. METHODS: In this proof-of-concept study, we performed bedside ultrasound-guided minimally invasive autopsy (US-MIA) in the ICU of critically ill COVID-19 patients using a structured protocol to obtain non-autolyzed tissue. Biopsies were assessed for their quality (vitality) and length of biopsy (mm) and for diagnosis. The efficiency of the procedure was monitored in five cases by recording the time of each step and safety issues by swabbing personal protective equipment and devices for viral contamination. FINDINGS: Ultrasound examination and tissue procurement required a mean time period of 13 min and 54 min, respectively. A total of 318 multiorgan biopsies were obtained from five patients. Quality and vitality standards were fulfilled, which not only allowed for specific histopathological diagnosis but also the reliable detection of SARS-CoV-2 virions in unexpected organs using electronic microscopy and RNA-expressing techniques. INTERPRETATION: Bedside multidisciplinary US-MIA allows for the fast and efficient acquisition of autolytic-free tissue and offers unappreciated potential to overcome the limitations of research in postmortem studies.

[Multimodal ultrasound techniques for the differential diagnosis of splenic lesions - A diagnostic challenge]. / Multimodale Ultraschalltechniken zur Differenzialdiagnose von Milzherden ­ eine diagnostische Herausforderung.

BACKGROUND: Splenic tumors are rare and can pose a differential diagnostic challenge, especially as an incidental imaging finding. Due to a lack of large scale biopsy studies the available literature is limited with respect to clear imaging criteria for dignity. OBJECTIVE: The present work is intended to show the chances of a targeted elicitation of the medical history as well as the possibilities and limitations of multimodal sonography in order to achieve the correct diagnosis of a splenic lesion using simple and gentle methods. MATERIAL AND METHODS: Selective literature search and clinical case studies. RESULTS: In the differential diagnostics of focal splenic lesions, information about pre-existing hemato-oncological or inflammatory rheumatological diseases is essential in order to correctly classify incidental findings in particular. In addition to B­mode ultrasound (B-US) and color-coded Doppler ultrasound (CD-US), contrast-enhanced ultrasound (CEUS) in particular provides crucial differential diagnostic information. While hyperechoic foci in B­US or arterially hypervascularized splenic foci in CD-US/CEUS are usually benign, hypoechoic and arterially hypoperfused foci in CD-US/CEUS must be further clarified. Although the ultrasound-guided biopsy of the spleen has a higher risk of bleeding than a liver biopsy, it is still the gentlest and most effective method for achieving the histological clarification of splenic lesions when the indications are correct. CONCLUSION: Through the combination of the medical history and multimodal ultrasound methods, if necessary supplemented by an ultrasound-guided biopsy, focal splenic lesions can be successfully classified in most cases with a direct impact on further clinical procedures.

Pulmonary Findings in Hospitalized COVID-19 Patients Assessed by Lung Ultrasonography (LUS) - A Prospective Registry Study.

PURPOSE: This prospective two-centre study investigated localisation-dependent lesion patterns in COVID-19 with standard lung ultrasonography (LUS) and their relationship with thoracic computed tomography (CT) and clinical parameters. MATERIALS AND METHODS: Between April 2020 and April 2021, 52 SARS-CoV-2-positive patients in two hospitals were examined by means of LUS for "B-lines", fragmented pleura, consolidation and air bronchogram in 12 lung regions and for pleural effusions. A newly developed LUS score based on the number of features present was correlated with clinical parameters (respiration, laboratory parameters) and the CT and analysed with respect to the 30- and 60-day outcome. All patients were offered an outpatient LUS follow-up. RESULTS: The LUS and CT showed a bilateral, partially posteriorly accentuated lesion distribution pattern. 294/323 (91%) of CT-detected lesions were pleural. The LUS score showed an association with respiratory status and C-reactive protein; the correlation with the CT score was weak (Spearman's rho = 0.339, p < 0.001). High LUS scores on admission were also observed in patients who were discharged within 30 days. LUS during follow-up showed predominantly declining LUS scores. CONCLUSION: The LUS score reflected the clinical condition of the patients. No conclusion could be made on the prognostic value of the LUS, because of the low event rate. The LUS and CT score showed no sufficient correlation. This is probably due to different physical principles, which is why LUS could be of complementary value.

Miniaturised ultrasound evaluation at the bedside.

PURPOSE: "Point-of-Care Ultrasound" (POCUS) is now a familiar term. Although the European Federation of Societies for Ultrasound in Medicine and Biology (ESFUMB) published a position paper about its usage (Nielsen et al. in Ultraschall Med 40(1):30-39. https://doi.org/10.1055/a-0783-2303 , 2019), there has not been much scientific focus on its utility in uro-nephrological clinical practice thus far. The aim of this study was to evaluate the present usage of pocket ultrasound devices at the bedside. METHODS: 27 investigators (all medical doctors with at least 6 months of experience in sonography) performed 280 bedside examinations using a pocket ultrasound device for common clinical issues. RESULTS: The most frequent indications included evaluation of hydronephrosis (147), volume management including assessment of dimension of the vena cava inferior (IVC) (195), detection of pleural, pericardial and abdominal effusions (113) as well as residual urine (52). In 90%, specific clinical questions were effectively answered by the pocket ultrasound device alone. CONCLUSIONS: POCUS can be useful in the uro-nephrological field. In the hands of an experienced investigator, it saves time and, when it is realised that departmental ultrasound is not cheap, there is also an economic benefit with applicability within both inpatient and outpatient clinic settings. While acknowledging its technical limits, pocket ultrasound devices may nevertheless be helpful in targeted situations for triage or for bedside follow-up exams after earlier high-end ultrasound-based diagnosis.

Ultrasound-based "CEUS-Bosniak"classification for cystic renal lesions: an 8-year clinical experience.

PURPOSE: Renal cysts comprise benign and malignant entities. Risk assessment profits from CT/MRI imaging using the Bosniak classification. While Bosniak-IIF, -III, and -IV cover complex cyst variants, Bosniak-IIF and -III stand out due to notorious overestimation. Contrast-enhanced ultrasound (CEUS) is promising to overcome this deficit but warrants standardization. This study addresses the benefits of a combined CEUS and CT/MRI evaluation of renal cysts. The study provides a realistic account of kidney tumor boards' intricacies in trying to validate renal cysts. METHODS: 247 patients were examined over 8 years. CEUS lesions were graded according to CEUS-Bosniak (IIF, III, IV). 55 lesions were resected, CEUS-Bosniak- and CT/MRI-Bosniak-classification were correlated with histopathological diagnosis. Interobserver agreement between the classifications was evaluated statistically. 105 lesions were followed by ultrasound, and change in CEUS-Bosniak-types and lesion size were documented. RESULTS: 146 patients (156 lesions) were included. CEUS classified 67 lesions as CEUS-Bosniak-IIF, 44 as CEUS-Bosniak-III, and 45 as CEUS-Bosniak-IV. Histopathology of 55 resected lesions revealed benign cysts in all CEUS-Bosniak-IIF lesions (2/2), 40% of CEUS-Bosniak-III and 8% of CEUS-Bosniak-IV, whereas malignancy was uncovered in 60% of CEUS-Bosniak-III and 92% of CEUS-Bosniak-IV. Overall, CEUS-Bosniak-types matched CT/MRI-Bosniak types in 58% (fair agreement, κ = 0.28). CEUS-Bosniak resulted in higher stages than CT/MRI-Bosniak (40%). Ultrasound follow-up of 105 lesions detected no relevant differences between CEUS-Bosniak-types concerning cysts size. 99% of lesions showed the same CEUS-Bosniak-type. CONCLUSION: The CEUS-Bosniak classification is an essential tool in clinical practice to differentiate and monitor renal cystic lesions and empowers diagnostic work-up and patient care.

[Clinical ultrasound in nephrology]. / Klinischer Ultraschall in der Nephrologie.

When used correctly, modern ultrasound diagnostics are helpful for the nephrologist especially in emergency situations on the ward, in dialysis and in the emergency admission to quickly make the correct diagnosis or as a diagnostic gatekeeper to initiate the correct next diagnostic and therapeutic steps in a time-saving manner. In addition to conventional B­mode/gray scale sonography and Doppler sonography, new ultrasound transducers with higher spatial resolution and above all contrast agent sonography have significantly expanded the technical possibilities and help nephrologists and internists to answer diagnostic and clinical questions. This particularly applies to the kidneys, which up to now could only be clarified by means of contrast-enhanced computed tomography or magnetic resonance imaging. This will allow the nephrologist in 2021 to amalgamate the clinical symptoms, imaging results and pathophysiological knowledge in an ideal, time-saving manner for the benefit of the patient.

EFSUMB 2020 Proposal for a Contrast-Enhanced Ultrasound-Adapted Bosniak Cyst Categorization - Position Statement.

The well-established Bosniak renal cyst classification is based on contrast-enhanced computed tomography determining the malignant potential of cystic renal lesions. Ultrasound has not been incorporated into this pathway. However, the development of ultrasound contrast agents coupled with the superior resolution of ultrasound makes it possible to redefine the imaging of cystic renal lesions. In this position statement, an EFSUMB Expert Task Force reviews, analyzes, and describes the accumulated knowledge and limitations and presents the current position on the use of ultrasound contrast agents in the evaluation of cystic renal lesions.

Sonography of the renal allograft: Correlation between doppler sonographic resistance index (RI) and histopathology.

INTRODUCTION: Allograft rejection (AR), chronic allograft injury (CAI) and acute tubular necrosis (ATN) can lead to renal allograft dysfunction after kidney transplantation. Interstitial fibrosis/tubular atrophy (Banff classification 2005) describes chronic allograft injury with no specific etiology, thus explaining the common final endpoint of various (immunologic and non immunologic) etiologies. The aim of this study was to evaluate correlations between the Doppler sonographic RI-values and histopathological changes of renal allografts biopsies during rejection, acute tubular necrosis and chronic allograft injury as well as the influence of donor and recipient features on the intrarenal RI-values. METHODS: 102 allograft biopsies and ultrasound reports of 69 patients with kidney transplantation performed at the hospital Klinikum rechts der Isar (Technische Universität München, Germany) between 2009 and 2013 were analyzed retrospectively (41 biopsies of living donors, 61 biopsies of deceased donors). Chronic allograft injury was described using the IFTA (interstitial fibrosis and tubular atrophy) or the ECAI score (extended chronic allograft injury score). The ECAI score was built out of the chronic histological lesions glomerulopathy, interstitial fibrosis, tubular atrophy and fibrous intimal thickening (cg + ci + ct + cv) of the BANFF scoring. RESULTS: Intrarenal RI-values were significantly higher in patients with allograft rejection than without rejection (median 0,79 vs. 0,73; inter quartile range: 0,20 vs. 0,13; p = 0,018). The same was found for T-and non-T cell mediated rejection (median 0,78 vs. 0,73; inter quartile range 0,20 vs. 0,13; p = 0,039). There were no significant differences in the RI-values between the subtypes of T-cell mediated rejection (type IA-IIB). Furthermore, there were no significant differences of RI-values regarding antibody-mediated rejection (present vs. not present) or type of rejection (T-cell- vs. antibody mediated rejection). Patients with rejection and simultaneously chronic allograft injury showed significantly higher RI-values than patients with only chronic allograft injury. Analyses using the IFTA or the ECAI score showed comparable results (IFTA p = 0,043; Score p = 0,021). The intrarenal RI-value was neither able to detect chronic allograft injury nor to distinguish between acute tubular necrosis and rejection. The intrarenal RI-value showed a significant correlation with recipient age (p < 0,001) but not with donor features. CONCLUSION: In summary, the intrarenal RI-value can indicate a rejection but gives no clear hint to acute tubular necrosis and cannot differentiate from it. Since patients with rejection can have normal RI-values, a biopsy should always be performed in case of suspected rejection. The intrarenal RI-value has no unambiguous validity to determine intrinsic values of the renal allograft, but should rather be understood and interpreted as a systemic parameter influenced by multiple factors.

Does standoff material affect acoustic radiation force impulse elastography? A preclinical study of a modified elastography phantom.

PURPOSE: This study was conducted to determine the influence of standoff material on acoustic radiation force impulse (ARFI) measurements in an elasticity phantom by using two different probes. METHODS: Using ARFI elastography, 10 observers measured the shear wave velocity (SWV, m/sec) in different lesions of an elasticity phantom with a convex 4C1 probe and a linear 9L4 probe. The experimental setup was expanded by the use of an interposed piece of porcine muscle as standoff material. The probe pressure on the phantom was registered. RESULTS: Faulty ARFI measurements occurred more often when quantifying the hardest lesion (74.0 kPa 4.97 m/sec) by the 9L4 probe with the porcine muscle as a standoff material interposed between the probe and the phantom. The success rate for ARFI measurements in these series was 52.4%, compared with 99.5% in the other series. The SWV values measured with the 9L4 probe were significantly higher (3.33±1.39 m/sec vs. 2.60±0.74 m/sec, P<0.001 in the group without muscle) and were closer to the reference value than those measured with the 4C1 probe (0.25±0.23 m/sec vs. 0.85±1.21 m/sec, P<0.001 in the same group). The SWV values measured when using the muscle as a standoff material were lower than those without the muscle (significant for 9L4, P=0.040). The deviation from the reference value and the variance increased significantly with the 9L4 probe if the muscle was in situ (B=0.27, P=0.004 and B=0.32, P<0.001). In our study, the pressure exerted by the operator had no effect on the SWV values. CONCLUSION: The presence of porcine muscle acting as a standoff material influenced the occurrence of failed measurements as well as the variance and the accuracy of the measured values. The linear high-frequency probe was particularly affected.

Multimodal Ultrasonographic Pathway of Parotid Gland Lesions.

Purpose To evaluate a multimodal pathway in solitary circumscribed parotid gland lesions (PL) to predict tumor dignity and to avoid repeat surgery. Materials and Methods 202 patients with PL underwent medical history, clinical examination, high-resolution B-mode ultrasound (US), real-time sonoelastography (RTE), color-coded duplex sonography (CDS), and contrast-enhanced ultrasound (CEUS). Malignancy was suspected when: 1. patients reported on previous cutaneous head and neck (H&N) malignancy; 2. patients presented synchronous cutaneous H&N malignancy and/or facial palsy; 3. US visualized poorly defined tumor borders and/or pathological cervical lymph nodes; 4. PL showed poor vascularization in CDS with enhanced perfusion kinetics in CEUS; 5. PL showed moderate/strong vascularization with delayed perfusion kinetics. Intraoperative frozen section was performed in PLs suspicious for malignancy, and surgery was extended when malignancy was confirmed. The sensitivity, specificity, negative, and positive predictive values (NPV/PPV) were calculated. Results Histology revealed 170 benign and 32 malignant PLs. Medical history, clinical examination, and B-mode US identified malignancy with a sensitivity/specificity of 77 %/98 %. After application of CDS and CEUS in the multimodal pathway, the sensitivity of malignant tumors increased to 91 %. The decreased specificity (81 %) was equalized by intraoperative frozen section (PPV 48 %, NPV 98 %). After application of the multimodal pathway, only 1 patient underwent repeat surgery. Conclusion The multimodal pathway is a useful method to predict dignity in PLs and reduces the number of repeat surgeries.

Preclinical evaluation of acoustic radiation force impulse measurements in regions of heterogeneous elasticity.

PURPOSE: The purpose of this study was to compare the reliability of ultrasound-based shear wave elastography in regions of homogeneous versus heterogeneous elasticity by using two different probes. METHODS: Using acoustic radiation force impulse (ARFI) elastography, we measured the shear wave velocity (SWV) in different lesions of an elastography phantom with the convex 4C1 probe and the linear 9L4 probe. The region of interest (ROI) was positioned in such a way that it was partly filled by one of the lesions (0%, 25%, 50%, 75%, and 100%) and partly by the background of the phantom (100%, 75%, 50%, 25%, and 0%, respectively). RESULTS: The success rate was 98.5%. The measured value and the reference value of SWV correlated significantly (r=0.89, P<0.001). Further, a comparison of the two probes revealed that there was no statistical difference in either the mean or the variance values. However, the deviation of SWV from the reference was higher in the case of the 9L4 probe than in the case of the 4C1 probe, both overall and in measurements in which the ROI contained structures of different elasticity (P=0.021 and P=0.002). Taking into account all data, for both probes, we found that there was a greater spread and deviation of the SWV from the reference value when the ROI was positioned in structures having different elastic properties (standard deviation, 0.02±0.01 m/sec vs. 0.04±0.04 m/sec; P=0.010; deviation from the reference value, 0.21±0.12 m/sec vs. 0.38±0.27 m/sec; P=0.050). CONCLUSION: Quantitative ARFI elastography was achievable in structures of different elasticity; however, the validity and the reliability of the SWV measurements decreased in comparison to those of the measurements performed in structures of homogeneous elasticity. Therefore, a convex probe is preferred for examining heterogeneous structures.

Comparison of a pocket-size ultrasound device with a premium ultrasound machine: diagnostic value and time required in bedside ultrasound examination.

PURPOSE: Time savings and clinical accuracy of a new miniature ultrasound device was investigated utilizing comparison with conventional high-end ultrasound instruments. Our objective was to determine appropriate usage and limitations of this diagnostic tool in internal medicine. METHODS: We investigated 28 patients from the internal-medicine department. Patients were examined with the Acuson P10 portable device and a Sonoline Antares instrument in a cross-over design. All investigations were carried out at the bedside; the results were entered on a standardized report form. The time for the ultrasound examination (transfer time, setting up and disassembly, switching on and off, and complete investigation time) was recorded separately. RESULTS: Mean time for overall examination per patient with the portable ultrasound device was shorter (25.0 ± 4.5 min) than with the high-end machine (29.4 ± 4.4 min; p < 0.001). When measuring the size of liver, spleen, and kidneys, the values obtained differed significantly between portable device and the high-end instrument. In our study, we identified 113 pathological ultrasound findings with the high-end ultrasound machine, while 82 pathological findings (73%) were concordantly detected with the portable ultrasound device. The main diagnostic strengths of the portable device were in the detection of ascites (sensitivity 80%), diagnosis of fatty liver, and identification of severe parenchymal liver damage. CONCLUSIONS: The clinical utility of portable ultrasound machines is limited. There will be clinical roles for distinct clinical questions such as detection of ascites or pleural effusion when used by experienced examiners. However, sensitivity in detecting multiple pathologies is not comparable to high-end ultrasound machines.