Development of a cellular assay as a personalized model for testing chronic wound therapeutics.

Exudates of non-healing wounds contain drivers of pathogenicity. We utilized >800 exudates from non-healing and healing wounds of diverse etiologies, collected by three different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to a) to differentiate between healing and non-healing wounds, b) follow the healing process of individual patients, and c) assess the effects of therapeutics for chronic wounds ex vivo. We observed a strong correlation between wound chronicity and inhibitory effects of individual exudates on fibroblast proliferation, with good diagnostic sensitivity (76-90%, depending on the sample collection method). Transition of a clinically non-healing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo non-healing wound exudates revealed an induction of inflammatory cytokine- and chemokine pathways and the unfolded protein response, indicating that these changes may contribute to the pathology of non-healing wounds. Testing the wound therapeutics platelet derived growth factor and silver sulfadiazine yielded responses in line with clinical experience and indicate the usefulness of the assay to search for and profile new therapeutics.

Improved Interpretation of Pulmonary Artery Wedge Pressures through Left Atrial Volumetry-A Cardiac Magnetic Resonance Imaging Study.

BACKGROUND: The pulmonary artery wedge pressure (PAWP) is regarded as a reliable indicator of left ventricular end-diastolic pressure (LVEDP), but this association is weaker in patients with left-sided heart disease (LHD). We compared morphological differences in cardiac magnetic resonance imaging (CMR) in patients with heart failure (HF) and a reduced left ventricular ejection fraction (LVEF), with or without elevation of PAWP or LVEDP. METHODS: We retrospectively identified 121 patients with LVEF < 50% who had undergone right heart catheterization (RHC) and CMR. LVEDP data were available for 75 patients. RESULTS: The mean age of the study sample was 63 ± 14 years, the mean LVEF was 32 ± 10%, and 72% were men. About 53% of the patients had an elevated PAWP (>15 mmHg). In multivariable logistic regression analysis, NT-proBNP, left atrial ejection fraction (LAEF), and LV end-systolic volume index independently predicted an elevated PAWP. Of the 75 patients with available LVEDP data, 79% had an elevated LVEDP, and 70% had concomitant PAWP elevation. By contrast, all but one patient with elevated PAWP and half of the patients with normal PAWP had concomitant LVEDP elevation. The Bland-Altman plot revealed a systematic bias of +5.0 mmHg between LVEDP and PAWP. Notably, LAEF was the only CMR variable that differed significantly between patients with elevated LVEDP and a PAWP ≤ or >15 mmHg. CONCLUSIONS: In patients with LVEF < 50%, a normal PAWP did not reliably exclude LHD, and an elevated LVEDP was more frequent than an elevated PAWP. LAEF was the most relevant determinant of an increased PAWP, suggesting that a preserved LAEF in LHD may protect against backward failure into the lungs and the subsequent increase in pulmonary pressure.

Genotypic cluster analysis of Neisseria gonorrhoeae reveals a spectrum of sexual mixing including among HIV-serodiscordant men who have sex with men.

BACKGROUND: Men who have sex with men (MSM) are more vulnerable to acquiring sexually transmitted infections (STIs). In 2019, for instance, 74% of European Neisseria gonorrhoeae (Ng) cases among males affected MSM. A recent report by the World Health Organization showed that most of the 2020' interim targets to end STIs by 2030 had not been met. A broadened understanding of STI transmission networks could guide future elimination strategies and reduce the STI burden. Therefore, we used whole-genome sequencing (WGS) to determine Ng-clusters and assess sexual mixing. METHODS: WGS was performed on Ng-isolates collected at the Medical University of Vienna, Austria and was used for core genome multi-locus sequencing typing cluster analysis. Epidemiologic and infection-specific details were extracted from medical records. RESULTS: Genomic analysis and demographic data were available for 415 isolates, and 43.9% (182/415) were allocated to 31 Ng-clusters. Nine clusters comprised samples from heterosexual individuals only (women N = 4, human immunodeficiency virus (HIV)-negative men N = 49, HIV-positive man N = 1), nine clusters included MSM only (HIV-negative N = 22, HIV-positive N = 13) and 13 clusters included both heterosexuals and MSM (HIV-negative N = 75, HIV-positive N = 18). Current use of HIV pre-exposure prophylaxis (PrEP) was reported by 22.8% of MSM. In multivariate analysis, only 'MSM' predicted clustering with isolates from HIV-positive individuals (adjusted odds ratio 10.24 (95% CI 5.02-20.90)). CONCLUSIONS: Sexual mixing of HIV-positive, HIV-negative MSM and non-MSM was frequently observed. Furthermore, HIV-serodiscordant clustering highlights the importance of PrEP rollout to avert HIV transmission. Our findings can inform future STI prevention strategies and continuous surveillance efforts are required to keep up with transmission dynamics.

Quantification of the rotating frame relaxation time T2ρ: Comparison of balanced spin-lock and continuous-wave Malcolm-Levitt preparations.

For the quantification of rotating frame relaxation times, the T2ρ relaxation pathway plays an essential role. Nevertheless, T2ρ imaging has been studied only to a small extent compared with T1ρ, and preparation techniques for T2ρ have so far been adapted from T1ρ methods. In this work, two different preparation concepts are compared specifically for the use of T2ρ mapping. The first approach involves transferring the balanced spin-locking (B-SL) concept of T1ρ imaging. The second and newly proposed approach is a continuous-wave Malcolm-Levitt (CW-MLEV) pulse train with zero echo times and was motivated from T2 preparation strategies. The modules are tested in Bloch simulations for their intrinsic sensitivity to field inhomogeneities and validated in phantom experiments. In addition, myocardial T2ρ mapping was performed in mice as an exemplary application. Our results demonstrate that the CW-MLEV approach provides superior robustness and thus suggest that established methods of T1ρ imaging are not best suited for T2ρ experiments. In the presence of field inhomogeneities, the simulations indicated an increased banding compensation by a factor of 4.1 compared with B-SL. Quantification of left ventricular T2ρ time in mice yielded more consistent results, and values in the range of 59.2-61.1 ms (R2 = 0.986-0.992) were observed at 7 T.

Rotary excitation of non-sinusoidal pulsed magnetic fields: Towards non-invasive direct detection of cardiac conduction.

PURPOSE: There is a need for high resolution non-invasive imaging methods of physiologic magnetic fields. The purpose of this work is to develop a MRI detection approach for non-sinusoidal magnetic fields based on the rotary excitation (REX) mechanism which was previously successfully applied for the detection of oscillating magnetic fields in the sub-nT range. METHODS: The new detection concept was examined by means of Bloch simulations, evaluating the interaction effect of spin-locked magnetization and low-frequency pulsed magnetic fields. The REX detection approach was validated under controlled conditions in phantom experiments at 3 T. Gaussian and sinc-shaped stimuli were investigated. In addition, the detection of artificial fields resembling a cardiac QRS complex, which is the most prominent peak visible on a magnetocardiogram, was tested. RESULTS: Bloch simulations demonstrated that the REX method has a high sensitivity to pulsed fields in the resonance case, which is met when the spin-lock frequency coincides with a non-zero Fourier component of the stimulus field. In the experiments, we found that magnetic stimuli of different durations and waveforms can be distinguished by their characteristic REX response spectrum. The detected REX amplitude was proportional to the stimulus peak amplitude (R2 > 0.98) and the lowest field detection was 1 nT. Furthermore, the detection of QRS-like fields with varying QRS durations yielded significant results in a phantom setup (p < 0.001). CONCLUSION: REX detection can be transferred to non-sinusoidal pulsed magnetic fields and could provide a non-invasive, quantitative tool for spatially resolved assessment of cardiac biomagnetism. Potential applications include the direct detection and characterization of cardiac conduction.

Resurgence of common respiratory viruses in patients with community-acquired pneumonia (CAP)-A prospective multicenter study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major global cause of death and hospitalization. Bacteria or community-acquired viruses (CARVs) cause CAP. COVID-19 associated restrictions effectively reduced the circulation of CARVs. OBJECTIVES: The aim of this study was to analyze the proportion of CARVs in adult patients with CAP from mid-2020 to mid-2023. Specifically, we aimed to compare the rate of influenza virus, SARS-CoV-2, and RSV detections in patients aged 18-59 years and ≥60 years. STUDY DESIGN: We analyze the proportion of 21 community-acquired respiratory viruses (CARVs) and three atypical bacteria (Bordetella pertussis, Legionella pneumophila, and Mycoplasma pneumoniae) in nasopharyngeal swab samples using molecular multiplex methods within the prospective, multicentre, multinational study of the German study Group CAPNETZ. We used stringent inclusion criteria throughout the study. RESULTS: We identified CARVs in 364/1,388 (26.2 %) patients. In detail, we detected SARS-CoV-2 in 210/1,388 (15.1 %), rhino-/enterovirus in 64/1,388 (4.6 %), influenza virus in 23/1,388 (1.6 %) and RSV in 17/1,388 (1.2 %) of all patients. We detected RSV and influenza more frequently in patients ≥60 years, especially in 22/23 compared to the previous season. None of the atypical bacteria were detected. CONCLUSIONS: Beginning in 2023, we demonstrate a re-emergence of CARVs in CAP patients. Effective vaccines or specific antiviral therapies for more than two thirds of the detected viral infections are currently available. High detection rates of vaccine-preventable viruses in older age groups support targeted vaccination campaigns.

Blood calprotectin as a biomarker for infection and sepsis - the prospective CASCADE trial.

BACKGROUND: Early in the host-response to infection, neutrophils release calprotectin, triggering several immune signalling cascades. In acute infection management, identifying infected patients and stratifying these by risk of deterioration into sepsis, are crucial tasks. Recruiting a heterogenous population of patients with suspected infections from the emergency department, early in the care-path, the CASCADE trial aimed to evaluate the accuracy of blood calprotectin for detecting bacterial infections, estimating disease severity, and predicting clinical deterioration. METHODS: In a prospective, observational trial from February 2021 to August 2022, 395 patients (n = 194 clinically suspected infection; n = 201 controls) were enrolled. Blood samples were collected at enrolment. The accuracy of calprotectin to identify bacterial infections, and to predict and identify sepsis and mortality was analysed. These endpoints were determined by a panel of experts. RESULTS: The Area Under the Receiver Operating Characteristic (AUROC) of calprotectin for detecting bacterial infections was 0.90. For sepsis within 72 h, calprotectin's AUROC was 0.83. For 30-day mortality it was 0.78. In patients with diabetes, calprotectin had an AUROC of 0.94 for identifying bacterial infection. CONCLUSIONS: Calprotectin showed notable accuracy for all endpoints. Using calprotectin in the emergency department could improve diagnosis and management of severe infections, in combination with current biomarkers. CLINICAL TRIAL REGISTRATION NUMBER: DRKS00020521.

Cardiac function in a large animal model of myocardial infarction at 7 T: deep learning based automatic segmentation increases reproducibility.

Cardiac magnetic resonance (CMR) imaging allows precise non-invasive quantification of cardiac function. It requires reliable image segmentation for myocardial tissue. Clinically used software usually offers automatic approaches for this step. These are, however, designed for segmentation of human images obtained at clinical field strengths. They reach their limits when applied to preclinical data and ultrahigh field strength (such as CMR of pigs at 7 T). In our study, eleven animals (seven with myocardial infarction) underwent four CMR scans each. Short-axis cine stacks were acquired and used for functional cardiac analysis. End-systolic and end-diastolic images were labelled manually by two observers and inter- and intra-observer variability were assessed. Aiming to make the functional analysis faster and more reproducible, an established deep learning (DL) model for myocardial segmentation in humans was re-trained using our preclinical 7 T data (n = 772 images and labels). We then tested the model on n = 288 images. Excellent agreement in parameters of cardiac function was found between manual and DL segmentation: For ejection fraction (EF) we achieved a Pearson's r of 0.95, an Intraclass correlation coefficient (ICC) of 0.97, and a Coefficient of variability (CoV) of 6.6%. Dice scores were 0.88 for the left ventricle and 0.84 for the myocardium.

Three-dimensional assessment of image distortion induced by active cardiac implants in 3.0T CMR.

CMR at 3.0T in the presence of active cardiac implants remains a challenge due to susceptibility artifacts. Beyond a signal void that cancels image information, magnetic field inhomogeneities may cause distorted appearances of anatomical structures. Understanding influencing factors and the extent of distortion are a first step towards optimizing the image quality of CMR with active implants at 3.0T. All measurements were obtained at a clinical 3.0T scanner. An in-house designed phantom with a 3D cartesian grid of water filled spheres was used to analyze the distortion caused by four representative active cardiac devices (cardiac loop recorder, pacemaker, 2 ICDs). For imaging a gradient echo (3D-TFE) sequence and a turbo spin echo (2D-TSE) sequence were used. The work defines metrics to quantify the different features of distortion such as changes in size, location and signal intensity. It introduces a specialized segmentation technique based on a reaction-diffusion-equation. The distortion features are dependent on the amount of magnetic material in the active implants and showed a significant increase when measured with the 3D TFE compared to the 2D TSE. This work presents a quantitative approach for the evaluation of image distortion at 3.0T caused by active cardiac implants and serves as foundation for both further optimization of sequences and devices but also for planning of imaging procedures.

Fusion of cellulose microspheres with pulp fibers: Creating an unconventional type of paper.

Cellulose microspheres (CMS) are a type of spherical regenerated cellulose particles with versatile properties which have been used as carrier materials in medical and technical applications. The integration of CMS into paper products opens up novel application scenarios for paper products in a wide range of fields. However, the incorporation of CMS carriers into paper products is challenging and hitherto no reports do exist in literature. Here, we present a feasibility study to incorporate up to 50 w.% CMS in paper hand sheets using retention aids. Our primary observations highlight the successful formation of uniform paper hand sheets retaining its tensile strengths at elevated CMS concentrations. Sheets with high CMS contents exhibit an increase in density and display enhanced surface smoothness - an outcome of a CMS layer forming atop the fiber base - which effectively bridges voids and rectifies surface irregularities as supported by Gurley testing, infinite focus microscopy and scanning electron microscopy. While our primary objective centered on the general feasibility to manufacture CMS-containing papers, the resulting composite scaffold carries significant potential as a platform for innovative, functional paper-based materials.

Scars are frequently found as late sequelae in individuals affected by the 2022 mpox outbreak.

BACKGROUND: The 2022 mpox outbreak continues, and while progress has been made in prevention strategies and potential treatment options, data on late sequelae following mpox are scarce. OBJECTIVE: This analysis aimed to assess the incidence of scar formation in individuals affected by the 2022 mpox outbreak. METHODS: All individuals diagnosed with mpox at the Department of Dermatology at the Medical University of Vienna in 2022 were included in this analysis. Follow-up data were collected throughout November 2023. 'Scar formation' was defined as having at least one scar at the former active mpox lesions. RESULTS: At our clinic, 28 cases of mpox presented between June 2022 and October 2022 and exclusively occurred in men who have sex with men (100%, 28/28), of whom 46% (13/28) were living with HIV, and 32% (9/28) were using pre-exposure prophylaxis (PrEP). Secondary bacterial infection of mpox lesions was suspected in six individuals, and all received systemic antibiotics. Overall, 26 were followed up in November 2023 after a median time of 15 months, and scar formations were found in 43% of cases. CONCLUSIONS: Our data provide insights into the late yet cumulating disease burden caused by the 2022 mpox outbreak. Highly effective prevention strategies are warranted to overcome the mpox epidemic and its potential late sequelae.

Advance directives in the emergency department-a systematic review of the status quo.

BACKGROUND: Providing individualised healthcare in line with patient wishes is a particular challenge for emergency healthcare professionals. Documentation of patient wishes (DPW), e.g. as advance directives, can guide clinicians in making end-of-life decisions that respect the patient's wishes and autonomy. However, patient centered decisions are hindered by limited availability of DPWs in emergency settings. OBJECTIVE: This systematic review aims to congregate present data on recorded rates for DPW existence and availability in the emergency department (ED) as well as contributing factors for these rates. METHODS: We searched MEDLINE, Google Scholar, Embase and Web of Science databases in September 2023. Publications providing primary quantitative data on DPW in the ED were assessed. Publications referring only to a subset of ED patients (other than geriatric) and investigating DPW issued after admission were excluded. RESULTS: A total of 22 studies from 1996 to 2021 were included in the analysis. Most were from the US (n = 12), followed by Australia (n = 4), Canada (n = 2), South Korea, Germany, the United Kingdom and Switzerland (n = 1 each). In the general adult population presenting to the ED, 19.9-27.8% of patients reported having some form of DPW, but only in 6.8% or less it was available on presentation. In the geriatric population, DPW rates (2.6-79%) as well as their availability (1.1-48.8%) varied widely. The following variables were identified as positive predictors of having DPW, among others: higher age, poorer overall health, as well as sociodemographic factors, such as female gender, having children, being in a relationship, higher level of education or a recent previous presentation to hospital. CONCLUSIONS: Existence and availability of a recorded DPW among ED patients was low in general and even in geriatric populations mostly well below 50%. While we were able to gather data on prevalence and predictors, this was limited by heterogeneous data. We believe further research is needed to explore the quality of DPW and measures to increase both rates of existence and availability of DPW in the ED.

High cure rates of Mycoplasma genitalium following empiric treatment with azithromycin alongside frequent detection of macrolide resistance in Austria.

BACKGROUND: Mycoplasma genitalium (MG) is an emerging sexually transmitted infection, often harboring resistance-associated mutations to azithromycin (AZM). Global surveillance has been mandated to tackle the burden caused by MG, yet no data are available for Austria. Thus, we aimed to investigate the prevalence of MG, disease characteristics, and treatment outcomes at the largest Austrian HIV-and STI clinic. METHODS: All MG test results at the Medical University of Vienna from 02/2019 to 03/2022 were evaluated. Azithromycin resistance testing was implemented in 03/2021. RESULTS: Among 2671 MG tests, 199 distinct and mostly asymptomatic (68%; 135/199) MG infections were identified, affecting 10% (178/1775) of all individuals. This study included 83% (1479/1775) men, 53% (940/1775) men who have sex with men (MSM), 31% (540/1754) HIV+, and 15% (267/1775) who were using HIV pre-exposure prophylaxis (PrEP). In logistic regression analysis, 'MSM' (aOR 2.55 (95% CI 1.65-3.92)), 'use of PrEP' (aOR 2.29 (95% CI 1.58-3.32)), and 'history of syphilis' (aOR 1.57 (95% CI 1.01-2.24) were independent predictors for MG infections. Eighty-nine percent (178/199) received treatment: 11% (21/178) doxycycline (2 weeks), 52% (92/178) AZM (5 days), and 37% ( 65/178) moxifloxacin (7-10 days) and 60% (106/178) had follow-up data available showing negative tests in 63% (5/8), 76% (44/58) and 85% (34/40), respectively. AZM resistance analysis was available for 57% (114/199)) and detected in 68% (78/114). Resistance-guided therapy achieved a cure in 87% (53/61), yet, empiric AZM-treatment (prior to 03/2021) cleared 68% (26/38). CONCLUSIONS: Mycoplasma genitalium was readily detected in this Austrian observational study, affected predominantly MSM and often presented as asymptomatic disease. We observed a worryingly high prevalence of AZM resistance mutations; however, empiric AZM treatment cleared twice as many MG infections as expected.

Sepsis incidence, suspicion, prediction and mortality in emergency medical services: a cohort study related to the current international sepsis guideline.

PURPOSE: Sepsis suspicion by Emergency Medical Services (EMS) is associated with improved patient outcomes. This study assessed sepsis incidence and recognition by EMS and analyzed which of the screening tools recommended by the Surviving Sepsis Campaign best facilitates sepsis prediction. METHODS: Retrospective cohort study of claims data from health insurances (n = 221,429 EMS cases), and paramedics' and emergency physicians' EMS documentation (n = 110,419); analyzed outcomes were: sepsis incidence and case fatality compared to stroke and myocardial infarction, the extent of documentation for screening-relevant variables and sepsis suspicion, tools' intersections for screening positive in identical EMS cases and their predictive ability for an inpatient sepsis diagnosis. RESULTS: Incidence of sepsis (1.6%) was similar to myocardial infarction (2.6%) and stroke (2.7%); however, 30-day case fatality rate was almost threefold higher (31.7% vs. 13.4%; 11.8%). Complete vital sign documentation was achieved in 8.2% of all cases. Paramedics never, emergency physicians rarely (0.1%) documented a sepsis suspicion, respectively septic shock. NEWS2 had the highest sensitivity (73.1%; Specificity:81.6%) compared to qSOFA (23.1%; Sp:96.6%), SIRS (28.2%; Sp:94.3%) and MEWS (48.7%; Sp:88.1%). Depending on the tool, 3.7% to 19.4% of all cases screened positive; only 0.8% in all tools simultaneously. CONCLUSION: Incidence and mortality underline the need for better sepsis awareness, documentation of vital signs and use of screening tools. Guidelines may omit MEWS and SIRS as recommendations for prehospital providers since they were inferior in all accuracy measures. Though no tool performed ideally, NEWS2 qualifies as the best tool to predict the highest proportion of septic patients and to rule out cases that are likely non-septic.

Rescue From Permanent Kidney Injury in Acute Thrombosis of Both Renal Veins, the Inferior Vena Cava, and Both Iliofemoral Veins by Catheter-Based Thrombectomy.

CASE: A 33-year-old man with previously diagnosed lupus membranous nephropathy presented with painful swelling in both legs. Laboratory tests revealed acute kidney injury, and imaging studies by duplex ultrasound and computed tomography scan showed acute thrombosis of both renal veins, the infrahepatic inferior vena cava, and both iliofemoral venous segments. Initially, pharmacomechanical thrombolysis led to an insufficient morphological result. The therapeutic breakthrough was achieved by catheter-based mechanical thrombectomy of the infrarenal vena cava and both renal veins, which successfully cleared all affected venous segments from thrombus, paralleled by improvement of the patient's condition. However, after 1 week, the patient experienced recurrent thrombosis of the right renal vein with hemorrhagic infarction of the right kidney. After further optimization of immunomodulatory and antithrombotic therapy, a repeated catheter-based mechanical thrombectomy resulted in sustained clinical improvement and preservation of renal venous drainage and kidney function. CONCLUSION: Extensive acute thrombosis of both renal veins, the inferior vena cava, and both iliofemoral venous segments is a rare emergency potentially threatening kidney function. Immediate effective thrombus removal is essential to preserve kidney function and can be achieved by catheter-based mechanical thrombectomy embedded in a comprehensive immunomodulatory and antithrombotic therapeutic concept. CLINICAL IMPACT: This case demonstrated the efficacy of a catheter-based therapeutic approach in patients with extensive thrombosis of the venous system. A catheter-based approach must be embedded in a comprehensive medical therapeutic concept, which is essential to achieve a sustainable result.

Asymptomatic lymphogranuloma venereum is commonly found among men who have sex with men in Austria.

BACKGROUND AND OBJECTIVES: Serovar L1-L3 of Chlamydia trachomatis (CT) causes lymphogranuloma venereum (LGV). A surge in LGV-cases has been observed among HIV-positive men who have sex with men (MSM). Discrimination between LGV and non-LGV is pivotal since it has major treatment implications. Here, we aimed to determine the prevalence and characteristics of LGV among CT-infections. PATIENTS AND METHODS: All CT-positive results from 04/2014-12/2021 at the four largest Austrian HIV and STI clinics were evaluated. Disease characteristics and patient demographics were analyzed. RESULTS: Overall, n  =  2,083 infections of CT were documented in n  =  1,479 individual patients: median age was 31.4 years, 81% were male, 59% MSM, 44% HIV-positive, 13% on HIV pre-exposure-prophylaxis. Available serovar analyses (61% [1,258/2,083]) showed L1-L3 in 15% (192/1,258). Considering only MSM with rectal CT-infection, LGV accounted for 23% (101/439). Cases of LGV vs. other CT-infections were primarily MSM (92% [177/192] vs. 62% [1,179/1,891], p < 0.001), more often HIV-positive (64% [116/180] vs. 46% [631/1,376]; p < 0.001) and had frequently concomitant syphilis infection (18% [32/180] vs. 7% [52/749]; p < 0.001). LGV commonly manifested as proctitis (38% [72/192]) whereas 45% (87/192) were asymptomatic. CONCLUSIONS: Lymphogranuloma venereum accounted for 23% of rectal CT-infections in MSM. Furthermore, 45% of all LGV-cases were asymptomatic. In the absence of CT-serovar analysis, a high LGV prevalence should be considered in risk-populations and guide empiric treatment selection.

A new approach to characterize cardiac sodium storage by combining fluorescence photometry and magnetic resonance imaging in small animal research.

Cardiac myocyte sodium (Na+) homoeostasis is pivotal in cardiac diseases and heart failure. Intracellular Na+ ([Na+]i) is an important regulator of excitation-contraction coupling and mitochondrial energetics. In addition, extracellular Na+ ([Na+]e) and its water-free storage trigger collagen cross-linking, myocardial stiffening and impaired cardiac function. Therefore, understanding the allocation of tissue Na+ to intra- and extracellular compartments is crucial in comprehending the pathophysiological processes in cardiac diseases. We extrapolated [Na+]e using a three-compartment model, with tissue Na+ concentration (TSC) measured by in vivo 23Na-MRI, extracellular volume (ECV) data calculated from T1 maps, and [Na+]i measured by in vitro fluorescence microscopy using Na+ binding benzofuran isophthalate (SBFI). To investigate dynamic changes in Na+ compartments, we induced pressure overload (TAC) or myocardial infarction (MI) via LAD ligation in mice. Compared to SHAM mice, TSC was similar after TAC but increased after MI. Both TAC and MI showed significantly higher [Na+]i compared to SHAM (around 130% compared to SHAM). Calculated [Na+]e increased after MI, but not after TAC. Increased TSC after TAC was primarily driven by increased [Na+]i, but the increase after MI by elevations in both [Na+]i and [Na+]e.

Accuracy of VO2 estimation according to the widely used Krakau formula for the prediction of cardiac output.

BACKGROUND: Invasive cardiac output (CO) is measured with the thermodilution (TD) or the indirect Fick method (iFM) in right heart catheterization (RHC). The iFM estimates CO using approximation formulas for oxygen consumption ([Formula: see text]O2), but there are significant discrepancies (> 20%) between both methods. Although regularly applied, the formula proposed by Krakau has not been validated. We compared the CO discrepancies between the Krakau formula with the reference (TD) and three established formulas and investigated whether alterations assessed in cardiac magnetic resonance imaging (CMR) determined the extent of the deviations. METHODS: This retrospective study included 188 patients aged 63 ± 14 years (30% women) receiving both CMR and RHC. The CO was measured with TD or with the iFM using the formulas by Krakau, LaFarge, Dehmer, and Bergstra for [Formula: see text]O2 estimation (iFM-K/-L/-D/-B). Percentage errors were calculated as twice the standard deviation of the difference between two CO methods divided by their means; a cut-off of < 30% was regarded as acceptable. The iFM and TD-derived CO ratio was built, and deviations > 20% were counted. Logistic regression analyses were performed to identify determinants of a deviation of > 20%. RESULTS: The TD-derived CO (5.5 ± 1.7 L/min) was significantly different from all iFM (K: 4.8 ± 1.6, L: 4.3 ± 1.6; D: 4.8 ± 1.5 L/min; B: 5.4 ± 1.8 L/min all p < 0.05). The iFM-K-CO differed from all methods (p < 0.001) except iFM­D (p = 0.19). Percentage errors between TD-CO and iFM-K/-L/-D/-B were all beyond the acceptance limit (44/45/44/43%), while percentage errors between iFM­K and other iFM were all < 16%. None of the parameters measured in CMR was predictive of a discrepancy of > 20% between both methods. CONCLUSION: The Krakau formula was comparable to other iFM in estimating CO levels, but none showed satisfactory agreement with the TD method. Improved derivation cohorts for [Formula: see text]O2 estimation are needed that better reflect today's patients undergoing RHC.