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The placement of cardiovascular implantable electronic devices (CIED) comes with a risk of adverse events (AE). AE comprise complications associated with the procedure and the device. CIED infection is a severe AE. Reported CIED infection rates are regionally differing and publications of contemporary large cohort data regarding CIED infections for Germany are lacking. This investigation provides rates of CIED infection related hospital admission and CIED infection related mortality in Germany. Data from Germany's largest healthcare insurance fund was screened for CIED procedures during the period: January to December 2015. These data included placement, revision with aim to up- or downgrade, generator substitution, early revision and partial or complete extraction using specific procedure codes for reimbursement. Among the total population of beneficiaries undergoing CIED procedures, International Classification of Diseases codes (ICD 10 GM), operational and procedural codes for partial or complete hardware removal were used to identify CIED infections and lead related endocarditis. To report the corresponding mortality rates, the hospital discharge status was documented. In 2015, from a population of more than 27 million beneficiaries, we identified the cohort of 60,296 patients (57.3% male) who underwent any invasive CIED procedure. Within three months from the index procedure, 1,595 patients developed a major CIED infection. 1,129 (1.87%) were related to the generator pocket and 466 (0.8%) were related to the transvenous proportions of the leads, mortality after those infections was 8.4% and 15.24%, respectively. In summary, our data reveals a higher prevalence of acute CIED infection than previously noted. The elevated number of additional procedures in cases of CIED infection implies a deficiency in infection awareness., Competing Interests: Declarations. Competing interests: BB currently holds or held the following positions during the last three years - medical consultant/ part of the advisory board of: Abbott, BiolineSupply, Boston Scientific, CRM Microport, CrosstecGmbH, DrugsalesLtd., Implicity, Kappamed, KimalPLC, M3 Medical/EcclipseMedical, Medival SRL, Medtronic, Philips/Spectranetics, SintecSRL, Tauro-ImplantGmbH, Tauropharm GmbH, Transcutan The other authors declare no competing interests., (© 2024. The Author(s).)

Aim: To evaluate the predictive value of preoperative echocardiographic parameters for occurrence of VAs in patients with preexisting ICD undergoing LVAD implantation., Methods and Results: All consecutive patients (n = 264) with previous ICD who underwent LVAD surgery between May 2011 and December 2019 at our institution were included. The patients were predominantly male (89%) with NICM (59%) and a mean age of 59 ± 10 years. All LVADs were continuous flow device (154 HVAD, 21 HeartMate II, and 89 HeartMate 3). A total of 102 (39%) patients had VAs in the first year after LVAD implantation. We compared echocardiographic parameters in patients with and without VAs before LVAD, at 1 month and 1 year after LVAD implantation. Increased pre-LVEDD ≥ 72 mm predicted the occurrence of VAs after LVAD implantation for ICM patients (HR: 2.9, 95% confidence interval (CI): [1.3-6.6], p = 0.012), while a larger pre-RVEDD ≥ 46 mm was predictive in NICM patients (HR: 2.8, (CI): [1.4-5.9], p = 0.004). Moreover, a larger RVEDD at 1 year after LVAD was highly associated with VAs in the first year after LVAD implantation (50 ± 10 vs. 45 ± 8 mm, p = 0.001). All patients demonstrated a significant decrease in LVEDD as well as a reduction in severity of mitral and tricuspid regurgitation during 1 year after LVAD implantation, reflecting left ventricular unloading through the LVAD., Conclusions: Larger left and right ventricular diameters before LVAD predict the occurrence of VAs after LVAD implantation in ICM and NICM patients. Persistent RV remodeling post-LVAD is also associated with VAs., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Introduction: Infection is a significant complication of cardiac implantable electronic device (CIED) therapy. The European TauroPace™ Registry investigates the safety and efficacy of TauroPace™ (TP), an antimicrobial solution containing taurolidine, designed to prevent CIED infections., Methods: This multicenter study included patients undergoing CIED procedures at participating centers where TP was used as a disinfectant for external hardware surfaces and an antiseptic for irrigating surgical sites. All patients eligible for CIED placement with adjunctive TP as the standard of care were included. Other aspects of CIED procedures adhered to current guidelines. Data on CIED-related infective endocarditis, CIED pocket infection, device and procedure-related complications, adverse events, and all-cause mortality were prospectively collected for 12 months. In cases of revision, the previous procedure was censored, and a new procedure was created. Binomial and Kaplan-Meier statistics were employed to analyze event rates., Results: From January 2020 to November 2022, TP was used in 822 out of 1170 CIED procedures. Among patients who completed the 3-month follow-up, no CIED pocket infections were observed, and one case of CIED-related infective endocarditis was reported. In the 12-month follow-up cohort, two additional local pocket CIED infections were observed, resulting in a total of three major CIED infections within 1 year after the CIED placement procedure. The 3-month and 12-month major CIED infection rates were 0.125% and 0.51%, respectively. During the observation a complication rate of 4.4% was reported. No adverse events related to TP were observed., Conclusions: TP appears to be effective and safe in preventing CIED infections., Clinicaltrials: gov Identifier: NCT04735666., (© 2024. The Author(s).)

Purpose of Review: Cardiovascular magnetic resonance (CMR) imaging excels in providing detailed three-dimensional anatomical information together with excellent soft tissue contrast and has already become a valuable tool for diagnostic evaluation, electrophysiological procedure (EP) planning, and therapeutical stratification of atrial or ventricular rhythm disorders. CMR-based identification of ablation targets may significantly impact existing concepts of interventional electrophysiology. In order to exploit the inherent advantages of CMR imaging to the fullest, CMR-guided ablation procedures (EP-CMR) are justly considered the ultimate goal., Recent Findings: Electrophysiological cardiovascular magnetic resonance (EP-CMR) interventional procedures have more recently been introduced to the CMR armamentarium: in a single-center series of 30 patients, an EP-CMR guided ablation success of 93% has been reported, which is comparable to conventional ablation outcomes for typical atrial flutter and procedure and ablation time were also reported to be comparable. However, moving on from already established workflows for the ablation of typical atrial flutter in the interventional CMR environment to treatment of more complex ventricular arrhythmias calls for technical advances regarding development of catheters, sheaths and CMR-compatible defibrillator equipment. CMR imaging has already become an important diagnostic tool in the standard clinical assessment of cardiac arrhythmias. Previous studies have demonstrated the feasibility and safety of performing electrophysiological interventional procedures within the CMR environment and fully CMR-guided ablation of typical atrial flutter can be implemented as a routine procedure in experienced centers. Building upon established workflows, the market release of new, CMR-compatible interventional devices may finally enable targeting ventricular arrhythmias., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Type 1 diabetes (T1D) arises from autoimmune-mediated destruction of insulin-producing pancreatic beta cells. Recent advancements in the technology of generating pancreatic beta cells from human pluripotent stem cells (SC-beta cells) have facilitated the exploration of cell replacement therapies for treating T1D. However, the persistent threat of autoimmunity poses a significant challenge to the survival of transplanted SC-beta cells. Genetic engineering is a promising approach to enhance immune resistance of beta cells as we previously showed by inactivating the Renalase ( Rnls ) gene. Here, we demonstrate that Rnls loss of function in beta cells shapes autoimmunity by mediating a regulatory natural killer (NK) cell phenotype important for the induction of tolerogenic antigen-presenting cells. Rnls -deficient beta cells mediate cell - cell contact-independent induction of hallmark anti-inflammatory cytokine Tgfβ1 in NK cells. In addition, surface expression of regulatory NK immune checkpoints CD47 and Ceacam1 is markedly elevated on beta cells deficient for Rnls . Altered glucose metabolism in Rnls mutant beta cells is involved in the upregulation of CD47 surface expression. These findings are crucial to better understand how genetically engineered beta cells shape autoimmunity, giving valuable insights for future therapeutic advancements to treat and cure T1D., Competing Interests: PY and SK are inventors on a patent application filed by the Joslin Diabetes Center that relates to the targeting of RNLS for the protection of transplanted SC-islets. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bode, Wei, Gruber, Li, Kissler and Yi.)

Aims: Simplified ablation technologies for pulmonary vein isolation (PVI) are increasingly performed worldwide. One of the most common complications following PVI are vascular access-related complications. Lately, venous closure systems (VCSs) were introduced into clinical practice, aiming to reduce the time of bed rest, to increase the patients' comfort, and to reduce vascular access-related complications. The aim of the present study is to compare the safety and efficacy of using a VCS to achieve haemostasis following single-shot PVI to the actual standard of care [figure-of-eight suture and manual compression (MC)]., Methods and Results: This is a prospective, multicentre, randomized, controlled, open-label trial performed at three German centres. Patients were randomized 1:1 to undergo haemostasis either by means of VCS (VCS group) or of a figure-of-eight suture and MC (F8 group). The primary efficacy endpoint was the time to ambulation, while the primary safety endpoint was the incidence of major periprocedural adverse events until hospital discharge. A total of 125 patients were randomized. The baseline characteristics were similar between the groups. The VCS group showed a shorter time to ambulation [109.0 (82.0, 160.0) vs. 269.0 (243.8, 340.5) min; P < 0.001], shorter time to haemostasis [1 (1, 2) vs. 5 (2, 10) min; P < 0.001], and shorter time to discharge eligibility [270 (270, 270) vs. 340 (300, 458) min; P < 0.001]. No major vascular access-related complication was reported in either group. A trend towards a lower incidence of minor vascular access-related complications on the day of procedure was observed in the VCS group [7 (11.1%) vs. 15 (24.2%); P = 0.063] as compared to the control group., Conclusion: Following AF ablation, the use of a VCS results in a significantly shorter time to ambulation, time to haemostasis, and time to discharge eligibility. No major vascular access-related complications were identified. The use of MC and a figure-of-eight suture showed a trend towards a higher incidence of minor vascular access-related complications., Competing Interests: Conflict of interest: R.R.T. is a consultant for Boston Scientific, Biotronik, Biosense Webster, and Abbott Medical, and he received speaker’s honoraria from Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and Lifetech and research grants from Abbott, Biosense Webster, and Lifetech. C.-H.H. received travel grants and research grants from Abbott Medical, Boston Scientific, Medtronic, Lifetech, Biosense Webster, and CardioFocus. He is a consultant for Boston Scientific, Biosense Webster, and Lifetech and received speaker honoraria from Abbott Medical, Boston Scientific, Medtronic, Biosense Webster, CardioFocus, Pfizer, BMS, C.T.I. GmbH, and Doctrina Med. K.-H.K. reports grants and personal fees from Abbott Vascular, Medtronic, and Biosense Webster outside the submitted work. C.E. received travel grants and research grants from Abbott, Boston Scientific, and Biosense Webster and speaker honoraria from Abbott, Boston Scientific, Biosense Webster, C.T.I. GmbH, and Doctrina Med. S.S.P. received travel grants and congress grants from Lifetech and an Educational Grant and speaker honoraria from Abbott Medical. J.V. received honoraria for lectures / talks: Abbott, Astra Zeneca, Pfizer, Boston Scientific, C.T.I., Doctrina Med, Medtronic and travel grants: Medtronic, Boston Scientific, Abbott, and is proctor for Boston Scientific. P.S. is Member of Advisory Board of Abbott, Biosense Webster, Boston Scientific and Medtronic. All other authors have no relevant disclosures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: High-power-short-duration (HPSD) ablation is an effective treatment for atrial fibrillation but poses risks of thermal injuries to the oesophagus and vagus nerve. This study aims to investigate incidence and predictors of thermal injuries, employing machine learning., Methods and Results: A prospective observational study was conducted at Leipzig Heart Centre, Germany, excluding patients with multiple prior ablations. All patients received Ablation Index-guided HPSD ablation and subsequent oesophagogastroduodenoscopy. A machine learning algorithm categorized ablation points by atrial location and analysed ablation data, including Ablation Index, focusing on the posterior wall. The study is registered in clinicaltrials.gov (NCT05709756). Between February 2021 and August 2023, 238 patients were enrolled, of whom 18 (7.6%; nine oesophagus, eight vagus nerve, one both) developed thermal injuries, including eight oesophageal erythemata, two ulcers, and no fistula. Higher mean force (15.8 ± 3.9 g vs. 13.6 ± 3.9 g, P = 0.022), ablation point quantity (61.50 ± 20.45 vs. 48.16 ± 19.60, P = 0.007), and total and maximum Ablation Index (24 114 ± 8765 vs. 18 894 ± 7863, P = 0.008; 499 ± 95 vs. 473 ± 44, P = 0.04, respectively) at the posterior wall, but not oesophagus location, correlated significantly with thermal injury occurrence. Patients with thermal injuries had significantly lower distances between left atrium and oesophagus (3.0 ± 1.5 mm vs. 4.4 ± 2.1 mm, P = 0.012) and smaller atrial surface areas (24.9 ± 6.5 cm2 vs. 29.5 ± 7.5 cm2, P = 0.032)., Conclusion: The low thermal lesion's rate (7.6%) during Ablation Index-guided HPSD ablation for atrial fibrillation is noteworthy. Machine learning based ablation data analysis identified several potential predictors of thermal injuries. The correlation between machine learning output and injury development suggests the potential for a clinical tool to enhance procedural safety., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Fully CMR-guided electrophysiological interventions (EP-CMR) have recently been introduced but data on the optimal CMR imaging protocol are scarce. This study determined the clinical utility of 3D non-selective whole heart steady-state free precession imaging using compressed SENSE (nsWHcs) for automatic segmentation of cardiac cavities as the basis for targeted catheter navigation during EP-CMR cavo-tricuspid isthmus ablation. Fourty-two consecutive patients with isthmus-dependent right atrial flutter underwent EP-CMR radiofrequency ablations. nsWHcs succeeded in all patients (nominal scan duration, 98 ± 10 s); automatic segmentation/generation of surface meshes of right-sided cavities exhibited short computation times (16 ± 3 s) with correct delineation of right atrium, right ventricle, tricuspid annulus and coronary sinus ostium in 100%, 100%, 100% and 95%, respectively. Point-by-point ablation adhered to the predefined isthmus line in 62% of patients (26/42); activation mapping confirmed complete bidirectional isthmus block (conduction time difference, 136 ± 28 ms). nsWHcs ensured automatic and reliable 3D segmentation of targeted endoluminal cavities, multiplanar reformatting and image fusion (e.g. activation time measurements) and represented the basis for precise real-time active catheter navigation during EP-CMR ablations of isthmus-dependent right atrial flutter. Hence, nsWHcs can be considered a key component in order to advance EP-CMR towards the ultimate goal of targeted substrate-based ablation procedures., (© 2024. The Author(s).)

In view of potential future changes of German food legislation with regard to cheese product quality parameters, this study aimed to evaluate the quality of whey protein-enriched semihard cheese (WPEC). Model WPEC was produced in a pilot plant and on an industrial scale by adding defined amounts of high-heat (HH) milk to the cheese milk and comprehensively analyzed during cheese processing. The dry matter, total protein, pure protein, fat, and sodium chloride content of six-week ripened cheese samples were not significantly different ( p < 0.05) when the technologically necessary heating of the curd was adapted to the amount of HH milk. However, the ripening, firmness, and melting behavior of WPEC was different compared to cheese without HH milk. During ripening, no formation of whey protein peptides was observed, but differences in the amount of some bitter peptides deriving from the casein fraction were found. Sensory data suggested a slightly more bitter taste perception by the panelists for the WPEC. Further technological adjustments are recommended to obtain marketable WPEC.

Background: Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described., Objective: To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission., Design: Retrospective matched cohort analysis., Setting: Academic medical center/pituitary center., Patients: Patients with CD with surgical remission and surgically treated NFPA., Measurements: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests., Results: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%)., Limitation: The small sample of patients with autoimmune disease limited identification of independent risk factors., Conclusion: Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger., Primary Funding Source: Recordati Rare Diseases Inc., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2024.

The quality of American diets, measured by the Healthy Eating Index (HEI), has remained stable and low since 2005. The Dietary Guidelines for Americans 2020-2025 call for research analyzing dietary patterns to determine how guidelines might be altered to increase healthy eating. The present paper seeks to determine the dietary quality of popular fad dietary patterns among Americans. A definition of "fad diet" was created, and Google Trends© was searched for popular diets to determine popular dietary patterns based on the fad diet definition. Finally, eight dietary patterns were identified for inclusion. One-week sample menus were created for each dietary pattern, maximizing alignment with the DGAs but staying within the dietary pattern parameters, and then scored according to the HEI 2015 to determine the dietary quality. Total HEI scores ranged from 26.7 (Carnivore) to 89.1 (Low-FODMAP); the six highest total HEI scores were in the range of 77.1-89.1 out of 100 points. This analytical approach showed that some of the included popular fad dietary patterns have the potential to attain a high dietary quality. Rather than suggesting one "best" diet or dietary pattern, there is opportunity to maximize dietary quality in the context of dietary patterns that are considered fad diets.

Background: Cardiac implantable electronic device (CIED) placement comes with certain complications. CIED infection is a severe adverse event related to CIED placement. In randomised controlled trials, the preoperative intravenous administration of antibiotics and the adjunctive use of an antibiotic mesh envelope resulted in significant reduction in infections related to cardiac implantable electronic devices. The adjunctive use of taurolidine for this purpose is relatively novel and not considered in the guidelines. The required evidence may consist of a set of clinical studies., Methods: The European TauroPace TM registry (ETPR) prospectively evaluates every consecutive invasive procedure involving any CIED with adjunct TauroPace™ use in the contributing centres. As the estimation of the infection rate needs to be defensible, only interventions registered prior to the procedure will be followed-up. The endpoint is a major cardiac implantable electronic device infection according to the novel CIED infection criteria (1). Secondary endpoints comprise all-cause mortality, complications, adverse events of all grades, and major CIED infections during all follow-up examinations. The follow-up times are three months, twelve months, and eventually 36 months, as acute, subacute, and long-term CIED infections are of interest., Results: As the rate of CIED infections is expected to be very low, this registry is a multicentre, international project that will run for several years. Several reports are planned. The analyses will be included in the case number calculations for future randomised controlled trials., Conclusions: The ETPR will accumulate large case numbers to estimate small event rates more precisely; we intend to follow up on participants for years to reveal possible late effects.

The proinflammatory cytokine interleukin-1β (IL-1β) is known to be upregulated in patients suffering from metabolic syndrome. IL-1β contributes to insulin resistance in obesity and type 2 diabetes, yet its influence on the intestinal microbiome is incompletely understood. The data presented here demonstrate that mice genetically deficient in IL-1β show a specific alteration of intestinal colonisation of a small group of bacteria. Especially Akkermansia muciniphila, a bacterium reported to be inversely associated with obesity, diabetes, cardiometabolic diseases and low-grade inflammation, showed increased colonisation in IL-1β knockout mice. In comparative microarray analysis from mucus scrapings of the colon mucosa of IL-1β knockout and wildtype mice, angiogenin 4 mRNA was strongly reduced in IL-1β knockout animals. Since the presence of angiogenin 4 in the culture medium showed a significant growth inhibition on A. muciniphila which was not detectable for other bacteria tested, IL-1β induced expression of angiogenin 4 is a strong candidate to be responsible for the IL-1β induced suppression of A. muciniphila colonisation. Thus, the data presented here indicate that IL-1β might be the lacking link between inflammation and suppression of A. muciniphila abundance as observed in a variety of chronic inflammatory disorders.

Control of tumour development and growth by the immune system critically defines patient fate and survival. What regulates the escape of colorectal tumours from destruction by the immune system remains currently unclear. Here, we investigated the role of intestinal synthesis of glucocorticoids in the tumour development during an inflammation-induced mouse model of colorectal cancer. We demonstrate that the local synthesis of immunoregulatory glucocorticoids has dual roles in the regulation of intestinal inflammation and tumour development. In the inflammation phase, LRH-1/Nr5A2-regulated and Cyp11b1-mediated intestinal glucocorticoid synthesis prevents tumour development and growth. In established tumours, however, tumour-autonomous Cyp11b1-mediated glucocorticoid synthesis suppresses anti-tumour immune responses and promotes immune escape. Transplantation of glucocorticoid synthesis-proficient colorectal tumour organoids into immunocompetent recipient mice resulted in rapid tumour growth, whereas transplantation of Cyp11b1-deleted and glucocorticoid synthesis-deficient tumour organoids was characterized by reduced tumour growth and increased immune cell infiltration. In human colorectal tumours, high expression of steroidogenic enzymes correlated with the expression of other immune checkpoints and suppressive cytokines, and negatively correlated with overall patients' survival. Thus, LRH-1-regulated tumour-specific glucocorticoid synthesis contributes to tumour immune escape and represents a novel potential therapeutic target., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Reactive oxygen species (ROS) are a family of highly reactive molecules with numerous, often pleiotropic functions within the cell and the organism. Due to their potential to destroy biological structures such as membranes, enzymes and organelles, ROS have long been recognized as harmful yet unavoidable by-products of cellular metabolism leading to "oxidative stress" unless counterbalanced by cellular anti-oxidative defense mechanisms. Phagocytes utilize this destructive potential of ROS released in high amounts to defend against invading pathogens. In contrast, a regulated and fine-tuned release of "signaling ROS" (sROS) provides essential intracellular second messengers to modulate central aspects of immunity, including antigen presentation, activation of antigen presenting cells (APC) as well as the APC:T cell interaction during T cell activation. This regulated release of sROS is foremost attributed to the specialized enzyme NADPH-oxidase (NOX) 2 expressed mainly in myeloid cells such as neutrophils, macrophages and dendritic cells (DC). NOX-2-derived sROS are primarily involved in immune regulation and mediate protection against autoimmunity as well as maintenance of self-tolerance. Consequently, deficiencies in NOX2 not only result in primary immune-deficiencies such as Chronic Granulomatous Disease (CGD) but also lead to auto-inflammatory diseases and autoimmunity. A comprehensive understanding of NOX2 activation and regulation will be key for successful pharmaceutical interventions of such ROS-related diseases in the future. In this review, we summarize recent progress regarding immune regulation by NOX2-derived ROS and the consequences of its deregulation on the development of immune disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vincent Jaquet reports a relationship with Hplus Therapeutics, Geneva that includes: board membership and equity or stocks. Heiko Weyd reports a relationship with Medraxa Therapeutics, Heidelberg that includes: board membership and equity or stocks. Heiko Weyd has patent issued to German Cancer Research Institute. Kevin Bode has patent pending to German Cancer Research Institute., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Type 1 diabetes (T1D) is caused by the immune-mediated loss of pancreatic β-cells that produce insulin. The latest advances in stem cell (SC) β-cell differentiation methods have made a cell replacement therapy for T1D feasible. However, recurring autoimmunity would rapidly destroy transplanted SC β-cells. A promising strategy to overcome immune rejection is to genetically engineer SC β-cells. We previously identified Renalase (Rnls) as a novel target for β-cell protection. Here we show that Rnls deletion endows β-cells with the capacity to modulate the metabolism and function of immune cells within the local graft microenvironment. We used flow cytometry and single-cell RNA sequencing to characterize β-cell graft-infiltrating immune cells in a mouse model for T1D. Loss of Rnls within transplanted β-cells affected both the composition and the transcriptional profile of infiltrating immune cells in favor of an anti-inflammatory profile with decreased antigen-presenting capacity. We propose that changes in β-cell metabolism mediate local immune regulation and that this feature could be exploited for therapeutic goals., Article Highlights: Protective Renalase (Rnls) deficiency impacts β-cell metabolism. Rnls-deficient β-cell grafts do not exclude immune infiltration. Rnls deficiency in transplanted β-cells broadly modifies local immune function. Immune cell in Rnls mutant β-cell grafts adopt a noninflammatory phenotype., (© 2023 by the American Diabetes Association.)

Background: We recently described a novel pacemaker-mediated arrhythmia in Abbott cardiac implantable electronic devices (CIED), called pseudo-RNRVAS, that mimics repetitive non-reentrant ventriculoatrial synchrony (RNRVAS), but can appear in patients with ventriculoatrial (VA) block. It is caused by sinus-p-waves, trapped in the post-ventricular atrial refractory period (PVARP), which mimic VA conduction. The p-waves are followed by atrial pacing during the myocardial refractory time, which can trigger atrial fibrillation (AF). Pseudo-RNRVAS and RNRVAS are probably more common than appreciated, but the recognition and differentiation of the two can be challenging because most CIEDs do not recognize and store them., Objective: We illustrate practical challenges in the assessment of Pseudo-RNRVAS and provide programming options that proved safe and effective for preventing Pseudo-RNRVAS and reducing the risk for typical RNRVAS., Methods and Results: We illustrate in 10 patients the characteristics of Pseudo-RNRVAS and their treatment. The outcome regarding the recurrence of pseudo-RNRVAS after 6 months of follow-up was collected. Inappropriate atrial pacing during pseudo-RNRVAS resulted in AF in six patients. After shortening the PVARP in nine, inactivation/reduction of rate response in four, and reduction of the basic pacing rate in one patient, pseudo-RNRVAS was avoided in eight patients and reduced in one. In one patient AF became permanent., Conclusions: Pseudo-RNRVAS is a pacemaker-mediated arrhythmia that can appear in patients without VA conduction and may lead to AF. The suggested adjustments of pacing parameters were safe and effective in preventing the arrhythmia., (© 2023 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Several technologies are available for incorporating whey proteins into a cheese matrix. However, there is no valid analytical method available to determine the whey protein content in matured cheese, to date. Consequently, the aim of the present study was to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of individual whey proteins based on specific marker peptides ('bottom-up' proteomic approach). Therefore, the whey protein-enriched model of the Edam-type cheese was produced in a pilot plant and on an industrial scale. Tryptic hydrolysis experiments were performed to evaluate the suitability of identified potential marker peptides (PMPs) for α-lactalbumin (α-LA) and β-lactoglobulin (β-LG). Based on the findings, α-LA and β-LG appeared to be resistant to proteolytic degradation during six weeks of ripening and no influence on the PMP was observed. Good levels of linearity (R 2 > 0.9714), repeatability (CVs < 5%), and recovery rate (80% to 120%) were determined for most PMPs. However, absolute quantification with external peptide and protein standards revealed differences in model cheese depending on the PMP, e.g., 0.50% ± 0.02% to 5.31% ± 0.25% for β-LG. As protein spiking prior to hydrolysis revealed differing digestion behavior of whey proteins, further studies are required to enable valid quantification in various cheese types.

Type 1 diabetes is characterized by the autoimmune destruction of the insulin-producing beta cells of the pancreas. A promising treatment for this disease is the transplantation of stem cell-derived beta cells. Genetic modifications, however, may be necessary to protect the transplanted cells from persistent autoimmunity. Diabetic mouse models are a useful tool for the preliminary evaluation of strategies to protect transplanted cells from autoimmune attack. Described here is a minimally invasive method for transplanting and imaging cell grafts in an adoptive transfer model of diabetes in mice. In this protocol, cells from the murine pancreatic beta cell line NIT-1 expressing the firefly luciferase transgene luc2 are transplanted subcutaneously into immunodeficient non-obese diabetic (NOD)-severe combined immunodeficient (scid) mice. These mice are simultaneously injected intravenously with splenocytes from spontaneously diabetic NOD mice to transfer autoimmunity. The grafts are imaged at regular intervals via non-invasive bioluminescent imaging to monitor the cell survival. The survival of mutant cells is compared to that of control cells transplanted into the same mouse.

Aims: Data on safety and efficacy of a non-fasting strategy in minimal invasive cardiac procedures are lacking. We assessed a non-fasting strategy compared with a fasting strategy regarding patient's well-being and safety in elective cardiac implantable electronic device (CIED) procedures., Methods and Results: In this randomized, single-blinded clinical trial, 201 patients (non-fasting = 100, fasting = 101) with a mean age of 72.0 ± 11.6 years (66.7% male) were assigned to a non-fasting strategy (solids/fluids allowed up to 1 h) or a fasting strategy (at least 6 h no solids and 2 h no fluids) before the procedure and analysed on an intention-to-treat basis. The co-primary outcomes were patients' well-being scores (based on numeric rating scale, 0-10) and incidence of intra-procedural food-related adverse events, including vomiting, perioperative pulmonary aspiration, and emergency intubation. Renal, haematological, and metabolic blood parameters and 30-day follow-up data were gathered. The summed pre-procedural patients' well-being score was significantly lower in the non-fasting group [non-fasting: 13.1 ± 9.6 vs. fasting: 16.5 ± 11.4, 95% confidence interval (CI) of mean difference (MD) -6.35 to -0.46, P = 0.029], which was mainly driven by significantly lower scores for hunger and tiredness in the non-fasting group (non-fasting vs. fasting; hunger: 0.9 ± 1.9 vs. 3.1 ± 3.2, 95% CI of MD -2.86 to -1.42, P < 0.001; tiredness: 1.6 ± 2.3 vs. 2.6 ± 2.7, 95% CI of MD -1.68 to -0.29, P = 0.023). No intra-procedural food-related adverse events were observed. Relevant blood parameters and 30-day follow-up did not show significant differences., Conclusion: These results showed that a non-fasting strategy is beneficial to a fasting one regarding patient's well-being and comparable in terms of safety for CIED procedures (NCT04389697)., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In Germany, more than half of the population has low health literacy. These people have difficulties in finding and classifying health-related information and adapting it to their own situation. Among them are many young people, highlighting the importance of interventions early in life to promote health literacy.This is where the "Fit in Health" program of the Health Information Services of the Helmholtz Munich Research Center and the German Cancer Research Center starts. The objective is to contribute to the promotion of different dimensions of health literacy among children and adolescents. To this end, innovative training formats for teachers and teaching materials for students at secondary levels I and II are being designed and evaluated. The major diseases cancer and diabetes mellitus are used as models to provide basic knowledge on their pathogenesis, prevention, treatment, and research. In addition, information about the structures of the healthcare system and materials to strengthen health literacy are provided. An accompanying evaluation collects indicator data on coverage and acceptance of the measures.Since 2018, the program has published 46 teaching materials and three course readers with background knowledge for teachers. Furthermore, 50 training courses have been held, with approximately 1600 teachers and multipliers taking part in face-to-face and online events by the end of 2021. More than 90% of the participants gave the respective events very good or good evaluations. Around 80% of the participants said they would like to include the topics taught in their lessons. Further expansion of the offers is planned. Testing of a set of materials with respect to the gain of health literacy in a sample of students is currently being prepared., (© 2022. The Author(s).)

Quality improvement plays a major role in healthcare, and numerous approaches have been developed to implement changes. However, the reasons for success or failure of the methods applied often remains obscure. Normalization process theory, recently developed in sociology, provides a flexible framework upon which to construct quality improvement. We sought to determine if examination of a successful quality improvement project, using normalization process theory and social marketing, provided insight into implementation. We performed a retrospective analysis of the steps taken to implement a pain management program in an electrophysiology clinic. We mapped these steps, and the corresponding social marketing tools used, to elements of normalization process theory. The combination of mapping implementation steps and marketing approaches to the theory provided insight into the quality-improvement process. Specifically, examination of the steps in the context of normalization process theory highlighted barriers to implementation at individual, group, and organizational levels. Importantly, the mapping also highlighted how facilitators were able to overcome the barriers with marketing techniques. Furthermore, integration with social marketing revealed how promotion of tangibility of benefits aided communication and how process co-creation between stakeholders enhanced value. Our implementation of a pain-management program was successful in a challenging environment composed of several stakeholder groups with entrenched initial positions. Therefore, we propose that the behavior change elements of normalization process theory combined with social marketing provide a flexible framework to initiate quality improvement.

Calcium signaling is ubiquitous in nematode development from fertilization to cell specification to apoptosis. Calcium also regulates dauer entry in Caenorhabditis elegans, which corresponds to the infective stage of parasitic nematodes. In diverse parasites such as Trypanosoma cruzi and Toxoplasma gondii calcium has been shown to regulate host cell entry and egress, and perturbing calcium signaling represents a possible route to inhibit infection and parasitism in these species. Sodium calcium exchangers are considered the most important mechanism of calcium efflux, and our lab has previously characterized the sodium calcium exchanger gene family in C. elegans and studied the diversity of this family across a subset of specific nematode species. Here we build upon these data and explore sodium calcium exchangers across 108 species of nematodes. Our data reveal substantial differences in sodium calcium exchanger counts across the Phylum and detail expansions and contractions of specific exchanger subtypes within certain nematode clades. Finally, we also provide evidence for a role of sodium calcium exchangers in parasite activation by examining differentially expressed genes in non-activated versus activated infective stage larvae. Taken together our findings paint a heterogeneous picture of sodium calcium exchanger evolution across the Phylum Nematoda that may reflect unique adaptations to free-living and parasitic lifestyles., (Copyright © 2021 Elsevier B.V. All rights reserved.)