[«Diabetes Drugs¼ without Diabetes: SGLT-2 Inhibitors].

INTRODUCTION: No other class of drugs has caused as much of a stir in the last decade as sodium-glucose linked transporter 2 inhibitors (SGLT-2i) or gliflozines. At the latest since the SGLT-2i originally developed as a diabetes mellitus drug unexpectedly also showed protective effects for heart and kidney in pivotal studies, they are now the talk of the town. Although the cellular and molecular mechanisms have not yet been clarified in all details, they have revolutionized therapeutic approaches for diabetes mellitus, heart failure independent of left ventricular ejection fraction, and nephropathies based on positive data available. The purpose of this article is to review the effects and postulated mechanisms of action of SGLT-2 inhibitors, particularly in heart failure and renal failure, and to outline their potential risks and side effects.

The role of daily adjustment disorder, depression and anxiety symptoms for the physical activity of cardiac patients.

BACKGROUND: Physical activity (PA) is crucial in the treatment of cardiac disease. There is a high prevalence of stress-response and affective disorders among cardiac patients, which might be negatively associated with their PA. This study aimed at investigating daily differential associations of International Classification of Diseases (ICD)-11 adjustment disorder, depression and anxiety symptoms with PA and sedentary behaviour (SB) during and right after inpatient cardiac rehabilitation. METHODS: The sample included N = 129 inpatients in cardiac rehabilitation, Mage = 62.2, s.d.age = 11.3, 84.5% male, n = 2845 days. Adjustment disorder, depression and anxiety symptoms were measured daily during the last 7 days of rehabilitation and for 3 weeks after discharge. Moderate-to-vigorous PA (MVPA), light PA (LPA) and SB were measured with an accelerometer. Bayesian lagged multilevel regressions including all three symptoms to obtain their unique effects were conducted. RESULTS: On days with higher adjustment disorder symptoms than usual, patients engaged in less MVPA, and more SB. Patients with overall higher depression symptoms engaged in less MVPA, less LPA and more SB. On days with higher depression symptoms than usual, there was less MVPA and LPA, and more SB. Patients with higher anxiety symptoms engaged in more LPA and less SB. CONCLUSIONS: Results highlight the necessity to screen for and treat adjustment disorder and depression symptoms during cardiac rehabilitation.

Case report: Central venous catheter thrombosis complicated by chronic thromboembolic disease/pulmonary hypertension in two children requiring parenteral nutrition.

Chronic thromboembolic pulmonary hypertension is a rare but life-threatening complication of long-term central venous catheters (CVC) in children. However, evidence in terms of potential treatment strategies and outcome data remains scarce. We describe two cases of CVC-related thrombosis (Hickman-catheter) complicated by recurrent pulmonary emboli. One patient experienced a complete thromboembolic obstruction of the right pulmonary artery with normal pulmonary pressures and the second patient suffered from a central thromboembolic obstruction of both pulmonary arteries associated with severe pulmonary hypertension. Both patients successfully underwent surgical thromboendarterectomy with deep hypothermic circulatory arrest.

Pulmonary Rehabilitation Outcomes of Post-Acute COVID-19 Patients during Different Waves of the Pandemic.

(1) Background: Between the beginning of the coronavirus pandemic and summer 2022, we distinguished four pandemic waves, with different characteristics of the affected patients. This study investigated the impact of patient characteristics on the outcome of inpatient pulmonary rehabilitation (PR). (2) Methods: Using a prospective approach, the characteristics of post-acute COVID-19 patients of the different waves who participated in inpatient PR were compared based on their assessments and results collected as part of PR (Cumulative Illness Rating Scale (CIRS), six-minute walk test (6-MWT), Pulmonary Function Testing (PFT), and Functional Independent Measurement (FIM). (3) Results: A total of 483 patients were included in the analysis (Wave 1 n = 51, Wave 2 n = 202, Wave 3 n = 84, Wave 4 n = 146). Compared to Wave 3 + 4, patients of Wave 1 + 2 were older (69 vs. 63 years; p < 0.001), had a significantly lower CIRS (13.0 vs. 14.7 points; p = 0.004), had significant better PFT (FVC: 73 vs. 68%pred; p = 0.009; DLCOSB: 58 ± 18 vs. 50 ± 17%pred; p = 0.001), and showed significantly more comorbidities (2.0 vs. 1.6 n/pers.; p = 0.009). Wave 3 + 4 showed significantly greater improvements according to the 6-MWT (147 vs. 188 m; p < 0.001) and the FIM (5.6 vs. 21.1 points; p < 0.001). (4) Conclusions: Patients of the COVID-19 infection waves differed significantly according to their anthropometric data, incidence of comorbidities, and impact of the infection. All cohorts achieved clinically relevant and significant functional improvements during PR, with significant higher improvements in Wave 3 + 4.

Predicting physical activity following cardiac rehabilitation: A longitudinal observational study.

PURPOSE: The adoption of a healthy lifestyle is crucial for patients with established cardiac diseases. However, many patients do not engage in regular physical activity in their everyday life. RESEARCH METHOD: The present study applied the health action process approach (HAPA) in an intensive longitudinal research design (n = 3,354 daily surveys) investigating intention towards physical activity and objectively measured physical activity in 137 cardiac patients (Mage = 62.1 years) during and after inpatient rehabilitation across 28 days. Self-reported HAPA variables were measured daily in online questionnaires at the end of each day. Theory-driven hypotheses were tested using linear multilevel models. RESULTS: One-third of the sample did not reach the recommended physical activity levels in the first weeks after discharge from rehabilitation. Results are mostly in line with the motivational HAPA phase at both levels of analysis; outcome expectations and self-efficacy were positively associated with intentions. Results for the volitional phase were partly in line with the HAPA. Daily deviations in previous-day planning and concurrent action control were positively associated with physical activity during and after cardiac rehabilitation. CONCLUSION: The results of this study partly speak towards the HAPA in predicting physical activity in cardiac patients, thereby replicating prior research. The HAPA framework offers guidance for motivating and empowering cardiac patients to be more active in their everyday life. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

3D printer platform and conductance feedback loop for automated imaging of uneven surfaces by liquid microjunction-surface sampling probe mass spectrometry.

RATIONALE: Molecular imaging of samples using mass spectrometric techniques, such as matrix-assisted laser desorption ionization or desorption electrospray ionization, requires the sample surface to be even/flat and sliced into thin sections (c. 10 µm). Furthermore, sample preparation steps can alter the analyte composition of the sample. The liquid microjunction-surface sampling probe (LMJ-SSP) is a robust sampling interface that enables surface profiling with minimal sample preparation. In conjunction with a conductance feedback system, the LMJ-SSP can be used to automatically sample uneven specimens. METHODS: A sampling stage was built with a modified 3D printer where the LMJ-SSP is attached to the printing head. This setup can scan across flat and even surfaces in a predefined pattern ("static sampling mode"). Uneven samples are automatically probed in "conductance sampling mode" where an electric potential is applied and measured at the probe. When the probe contacts the electrically grounded sample, the potential at the probe drops, which is used as a feedback signal to determine the optimal position of the probe for sampling each location. RESULTS: The applicability of the probe/sensing system was demonstrated by first examining the strawberry tissue using the "static sampling mode." Second, porcine tissue samples were profiled using the "conductance sampling mode." With minimal sample preparation, an area of 11 × 15 mm was profiled in less than 2 h. From the obtained results, adipose areas could be distinguished from non-adipose parts. The versatility of the approach was further demonstrated by directly sampling the bacteria colonies on agar and resected human kidney (intratumoral hemorrhage) specimens with thicknesses ranging from 1 to 4 mm. CONCLUSION: The LMJ-SSP in conjunction with a conductive feedback system is a powerful tool that allows for fast, reproducible, and automated assessment of uneven surfaces with minimal sample preparation. This setup could be used for perioperative assessment of tissue samples, food screening, and natural product discovery, among others.

Hyperspectral Visualization-Based Mass Spectrometry Imaging by LMJ-SSP: A Novel Strategy for Rapid Natural Product Profiling in Bacteria.

Mass spectrometry imaging (MSI) has been widely used to discover natural products (NPs) from underexplored microbiological sources. However, the technique is limited by incompatibility with complicated/uneven surface topography and labor-intensive sample preparation, as well as lengthy compound profiling procedures. Here, liquid micro-junction surface sampling probe (LMJ-SSP)-based MSI is used for rapid profiling of natural products from Gram-negative marine bacteria Pseudoalteromonas on nutrient agar media without any sample preparation. A conductance-based autosampling platform with 1 mm spatial resolution and an innovative multivariant analysis-driven method was used to create one hyperspectral image for the sampling area. NP discovery requires general spatial correlation between m/z and colony location but not highly precise spatial resolution. The hyperspectral image was used to annotate different m/z by straightforward color differences without the need to directly interrogate the spectra. To demonstrate the utility of our approach, the rapid analysis of Pseudoalteromonas rubra DSM6842, Pseudoalteromonas tunicata DSM14096, Pseudoalteromonas piscicida JCM20779, and Pseudoalteromonas elyakovii ATCC700519 cultures was directly performed on Agar. Various natural products, including prodiginine and tambjamine analogues, were quickly identified from the hyperspectral image, and the dynamic extracellular environment was shown with compound heatmaps. Hyperspectral visualization-based MSI is an efficient and sensitive strategy for direct and rapid natural product profiling from different Pseudoalteromonas strains.

Impact of first-line use of caplacizumab on treatment outcomes in immune thrombotic thrombocytopenic purpura.

BACKGROUND: The von Willebrand factor-directed nanobody caplacizumab has greatly changed the treatment of immune thrombotic thrombocytopenic purpura (iTTP) in recent years. Data from randomized controlled trials established efficacy and safety. OBJECTIVES: This study aims to address open questions regarding patient selection, tailoring of therapy duration, obstacles in prescribing caplacizumab in iTTP, effect on adjunct treatment, and outcomes in the real-world setting. METHODS: We report retrospective, observational cohorts of 113 iTTP episodes treated with caplacizumab and 119 historical control episodes treated without caplacizumab. We aggregated data from the caplacizumab phase II/III trials and real-world data from France, the United Kingdom, Germany, and Austria (846 episodes, 396 treated with caplacizumab, and 450 historical controls). RESULTS: Caplacizumab was efficacious in iTTP, independent of the timing of therapy initiation, but curtailed the time of active iTTP only when used in the first-line therapy within 72 hours after diagnosis and until at least partial ADAMTS13-activity remission. Aggregated data from multiple study populations showed that caplacizumab use resulted in significant absolute risk reduction of 2.87% for iTTP-related mortality (number needed to treat 35) and a relative risk reduction of 59%. CONCLUSION: Caplacizumab should be used in first line and until ADAMTS13-remission, lowers iTTP-related mortality and refractoriness, and decreases the number of daily plasma exchange and hospital stay. This trial is registered at www. CLINICALTRIALS: gov as #NCT04985318.

Differential associations of emotional and physical domains of the MacNew Heart with changes in 6-min walking test.

AIMS: Cardiac rehabilitation (CR), a key component of secondary prevention in cardiac patients, contributes fundamentally to improved cardiovascular health outcomes. Health-related quality of life (HRQOL) represents a widely employed outcome measure in CR, yet, its predictive properties on exercise capacity change during CR are poorly understood. Aim of this study was to examine the association between baseline HRQOL and its subdomains on improvement of exercise capacity during CR. METHODS: Study participants were 13,717 inpatients of six Swiss CR clinics from 2012 to 2018. We measured HRQOL at admission to CR with the MacNew Heart (MNH) questionnaire and exercise capacity at admission and discharge using the six minutes walking test (6MWT). Following factorial analyses, we performed univariate and multivariate analyses to test the predictive properties of baseline global HRQOL and its domains for improvement in exercise capacity, adjusting for demographic and clinical characteristics. RESULTS: Mean improvement in 6MWT was 114 m (SD = 90), achieved after 17.4 days (SD = 5.5). Lower emotional HRQOL (b = 7.85, p = < .001, 95% CI [- 5.67, 10.03]) and higher physical HRQOL (b = - 5.23, p < .001, 95% CI [- 6.56, - 3.90]) were associated with less improvement in the 6MWT. Global MNH and social HRQOL showed no association with exercise capacity improvement. CONCLUSION: Patients entering CR with low emotional and high physical HRQOL are at risk for a lower gain in exercise capacity during CR. Global MNH alone does not provide a reliable assessment of HRQOL; thus a focus on specific domains of HRQOL is needed.

Sex and age as predictors of health-related quality of life change in Phase II cardiac rehabilitation.

AIMS: Cardiac rehabilitation (CR) not only improves cardiovascular outcomes, but also health-related quality of life (HRQOL). Unfortunately, CR is still underutilized, especially among women and older patients. Aim of this study was to highlight age- and sex-specific effects of inpatient CR on HRQOL. METHODS AND RESULTS: From 2012 to 2018, 18 459 patients were prospectively assessed in six Swiss CR clinics. Of these, we retrospectively analysed a final sample of 8286 patients with a mean (standard deviation) age of 67.8 (11.3) in men and 72.2 (11.3) in women. HRQOL was measured at CR entry and discharge. In multivariable analyses, sex- and age-specific changes in HRQOL throughout CR were estimated, adjusting for baseline HRQOL and clinical characteristics. Participants of both sexes improved significantly (P < 0.001) in all domains of HRQOL during CR. Women reported significantly lower social (P < 0.001) and emotional (P < 0.001) HRQOL than men at CR entry. Female sex predicted greater improvement in social (F = 19.63, P < 0.001), emotional (F = 27.814, P < 0.001), and physical HRQOL (F = 20.473, P < 0.001). In a subgroup of n = 2632 elderly patients (>75 years), female sex predicted greater changes in emotional (F = 15.738, P < 0.001) and physical (F = 6.295, P = 0.012), but not in social HRQOL. CONCLUSION: Women report poorer HRQOL at CR entry compared with men, but in turn particularly benefit from CR in this regard. Our results indicate that sex- and age-specific needs of patients should be considered.

Implementation of a Novel Medication Regimen Following Cardiac Rehabilitation: an Application of the Health Action Process Approach.

BACKGROUND: Medication adherence is an indispensable prerequisite for the long-term management of many chronic diseases. However, published literature suggests that non-adherence is widely prevalent. Health behavior change theories can help understand the underlying processes and allow the accumulation of knowledge in the field. The present study applied the health action process approach (HAPA) in an intensive longitudinal research design to investigate medication adherence in patients after discharge from inpatient cardiac rehabilitation. METHOD: In total, n = 139 patients (84.9% male, Mage = 62.2 years) completed n = 2,699 daily diaries in the 22 days following discharge from inpatient cardiac rehabilitation. Patients' intentions to take medication and predictors were assessed in daily end-of-day questionnaires. Adherence to medication was measured subjectively (self-report) and objectively. Multilevel modeling was applied to disentangle the between- and within-person level. RESULTS: Higher levels of risk awareness and self-efficacy were positively associated with intentions to take medication at both levels of analysis. Contrary to theoretical assumptions, positive outcome expectations were not associated with intention, neither between- nor within-person. In contrast to published literature, patients showed very high medication adherence (95.2% self-report, 92.2% objectively). CONCLUSION: In line with the theoretical assumptions, the results showed that risk awareness and self-efficacy are promising modifiable factors that could be targeted to motivate patients to take medication as prescribed. Daily measurements revealed that patients took their medication as prescribed; thus, future studies should make every effort to recruit patients vulnerable to non-adherence to avoid ceiling effects.

Fast and Efficient Image Novelty Detection Based on Mean-Shifts.

Image novelty detection is a repeating task in computer vision and describes the detection of anomalous images based on a training dataset consisting solely of normal reference data. It has been found that, in particular, neural networks are well-suited for the task. Our approach first transforms the training and test images into ensembles of patches, which enables the assessment of mean-shifts between normal data and outliers. As mean-shifts are only detectable when the outlier ensemble and inlier distribution are spatially separate from each other, a rich feature space, such as a pre-trained neural network, needs to be chosen to represent the extracted patches. For mean-shift estimation, the Hotelling T2 test is used. The size of the patches turned out to be a crucial hyperparameter that needs additional domain knowledge about the spatial size of the expected anomalies (local vs. global). This also affects model selection and the chosen feature space, as commonly used Convolutional Neural Networks or Vision Image Transformers have very different receptive field sizes. To showcase the state-of-the-art capabilities of our approach, we compare results with classical and deep learning methods on the popular dataset CIFAR-10, and demonstrate its real-world applicability in a large-scale industrial inspection scenario using the MVTec dataset. Because of the inexpensive design, our method can be implemented by a single additional 2D-convolution and pooling layer and allows particularly fast prediction times while being very data-efficient.

Discontinuously Dewetting Solvent Arrays: Droplet Formation and Poly-Synchronous Surface Extraction for Mass Spectrometry Imaging Applications.

We describe a new liquid tissue stamping method called poly-synchronous surface extraction (PSSE) that utilizes an omniphobic substrate patterned with hydrophilic surface energy traps (SETs), which when wet with a solvent form a dense microdroplet array. When contacted with a tissue sample, each droplet locally extracts analytes from the tissue surface, which subsequentially can be analyzed by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-IMS) or ambient ionization-MS techniques. Optimization of the patterned surface with six different solvents was carried out to increase the droplet density, height, and reproducibility of volume deposition. Once optimized, sister slices of a strawberry (Fragaria × ananassa) were spatially extracted using the PSSE technique and the chemical distribution of selected compounds was analyzed with both MALDI-IMS and a lower resolution but faster ambient liquid microjunction surface sampling probe (LMJ-SSP) approach. Heat maps for target analytes for the PSSE approach are compared to those produced using traditional MALDI-IMS analysis. The PSSE method aligned well with direct analysis and demonstrated the potential to increase the speed of ambient MS tissue imaging techniques by decreasing the number of steps required for sample preparation.

[Child with a vascularized throat mass]. / Kind mit gefäßreichem "Kloß" im Hals.

We report the case of an 11-year-old girl with difficultly speaking and a history of singular, self-limiting oral bleeding. Clinical and radiological examination in the emergency room showed a vascularized tumor of the base of the tongue, which almost completely occluded the oropharynx. After complex anesthesiologic preparation and endoluminal embolization, the tumor was safely removed by transoral laser microsurgery. Histology revealed a rare benign schwannoma of the oropharynx. Further clinical examinations and genetic screening were recommended.

Rapid Mass Spectrometric Calibration and Standard Addition Using Hydrophobic/Hydrophilic Patterned Surfaces and Discontinuous Dewetting.

The rapid calibration chip (RCC) is a device that uses the fast and reproducible wetting behavior of hydrophilic/hydrophobic patterned surfaces to confine a series of differently sized droplets on a substrate to obtain a calibration curve. Multiple series of droplets can be formed within seconds by dipping an RCC into a calibration solution. No pipetting, sequential droplet deposition, or advanced equipment is required. The performance and reproducibility of RCCs were evaluated with an electrospray ionization triple-quadrupole mass spectrometer equipped with a liquid microjunction-surface sampling probe (LMJ-SSP) that allows for fast sampling of surfaces. Using circular hydrophilic areas with diameters ranging from 0.25 to 2.00 mm, liquid volumes of 4.6-70.6 nL could be deposited. Furthermore, the use of a second hydrophobic/hydrophilic patterned transfer chip can be used to add internal standard solutions to each calibration spot of the RCC, allowing to transfer a liquid volume of 22.5 nL.

MMP-2 knockdown blunts age-dependent carotid stiffness by decreasing elastin degradation and augmenting eNOS activation.

AIMS: Arterial stiffness is a hallmark of vascular ageing that precedes and strongly predicts the development of cardiovascular diseases. Age-dependent stiffening of large elastic arteries is primarily attributed to increased levels of matrix metalloproteinase-2 (MMP-2). However, the mechanistic link between age-dependent arterial stiffness and MMP-2 remains unclear. Thus, we aimed to investigate the efficacy of MMP-2 knockdown using small-interfering RNA (siRNA) on age-dependent arterial stiffness. METHODS AND RESULTS: Pulse wave velocity (PWV) was assessed in right carotid artery of wild-type (WT) mice from different age groups. MMP-2 levels in the carotid artery and plasma of young (3 months) and old (20-25 months) WT mice were determined. Carotid PWV as well as vascular and circulating MMP-2 were elevated with increasing age in mice. Old WT mice (18- to 21-month old) were treated for 4 weeks with either MMP-2 or scrambled (Scr) siRNA via tail vein injection. Carotid PWV was assessed at baseline, 2 and 4 weeks after start of the treatment. MMP-2 knockdown reduced vascular MMP-2 levels and attenuated age-dependent carotid stiffness. siMMP-2-treated mice showed increased elastin-to-collagen ratio, lower plasma desmosine (DES), enhanced phosphorylation of endothelial nitric oxide synthase (eNOS), and higher levels of vascular cyclic guanosine monophosphate (cGMP). An age-dependent increase in direct protein-protein interaction between MMP-2 and eNOS was also observed. Lastly, DES, an elastin breakdown product, was measured in a patient cohort (n = 64, 23-86 years old), where carotid-femoral PWV was also assessed; here, plasma levels of DES directly correlated with age and arterial stiffness. CONCLUSION: MMP-2 knockdown attenuates age-dependent carotid stiffness by blunting elastin degradation and augmenting eNOS bioavailability. Given the increasing clinical use of siRNA technology, MMP2 knockdown should be investigated further as a possible strategy to mitigate age-dependent arterial stiffness and related CV diseases.

Depression and anxiety in cardiac rehabilitation: differential associations with changes in exercise capacity and quality of life.

BACKGROUND: Cardiac rehabilitation (CR) has been successful in improving exercise capacity (EC) and quality of life (QoL). However, depression and anxiety are highly prevalent among cardiac patients and might represent risk factors for rehabilitation outcomes. The aim of this study was to investigate the role of depression and anxiety as possible independent risk factors for CR outcomes. METHODS: The study applied a pre-post-design. The sample comprised N = 3'434 cardiac disease patients taking part in a Swiss inpatient CR center. Variables measured at the beginning (T1) and end of rehabilitation (T2) included depression and anxiety (HADS), EC, and QoL (MacNew). A path analysis was conducted. RESULTS: Depression at T1 had a significant negative relationship with improvements in EC and in all aspects of QoL during rehabilitation. Anxiety at T1 was positively related to improvements in EC and in emotional and physical QoL. Improvements in depression during CR were positively related with improvements in all outcomes. Improvements in anxiety showed no significant association with the outcomes. CONCLUSION: Depression and anxiety should be screened for during CR. Depression should be treated due to the negative association found with rehabilitation outcomes. Underlying mechanisms of the positive association of anxiety with rehabilitation outcomes need further investigation.

Cardiac Rehabilitation in Patients With Ventricular Assist Device.

PURPOSE: The aim of this study was to investigate changes in exercise capacity (EC) and quality of life (QoL) of patients with ventricular assist devices (VADs) during cardiac rehabilitation (CR). METHODS: Data from patients with VAD implantation and subsequent CR between 2007 and 2017 were analyzed retrospectively. Measures of the 6-min walk test [6MWT] distance, Functional Independence Measure [FIM], ergometry, MacNew Heart Disease Questionnaire [MNH], and Hospital Anxiety and Depression Scale [HADS] at entry and discharge were examined. RESULTS: Data from 110 patients (age 53 ± 12 yr; male 82%) were analyzed. Patients improved during CR significantly in the 6MWT (114 ± 85 m, P < .001), ergometry (20 ± 17 W, P = .002), FIM (8 ± 7 points, P < .001), and MNH (0.8 ± 0.7 points, P < .001). Initial HADS levels were high with a mean value of 9 and did not improve during CR (-0.4 ± 5 points, P = .637). Significant differences of improvements in the 6MWT were observed between left and biventricular VAD (129 ± 90 m vs 85 ± 67 m, P = .043) as well as destination therapy and bridge-to-transplant (184 ± 88 m vs 102 ± 82 m, P = .005). CONCLUSIONS: Patients with VAD implantation had statistically and clinically significant improvements in EC and QoL as assessed with the MNH during CR. Patients on destination therapy showed a larger benefit from CR than bridge-to-transplant patients and patients with left VAD improved more than biventricular VAD patients.