Symptom severity reflected by NYHA grade is independently associated with pruritus in chronic heart failure patients.

BACKGROUND: Pruritus is a symptom profoundly impairing patients' quality of life (QoL). It is a common symptom in chronic heart failure (CHF) patients of yet unknown nature. The aim of this study was to evaluate the risk factors of pruritus in CHF patients. METHODS: For this monocentric, prospective cohort study, CHF patients were recruited and CHF symptoms, comorbidities and drug intake were assessed using a structured report. Additionally, a questionnaire evaluated pruritus symptoms. Detailed medical histories including laboratory test results were retrieved from patient files for all participants. RESULTS: We evaluated data from 550 CHF patients. Of those, 25.3% reported pruritus to occur frequently (3-5 times per week), often (1-2 times per week) or daily. Patients of higher NYHA classes (NYHA III + IV) experienced significantly more pruritus (31.2%) than lower NYHA classes (NYHA I + II) (21.1%, p = 0.024). Patients with pruritus reported disproportionately often concomitant stasis dermatitis (p = 0.026) and chronic lung disease (p = 0.014). Other parameters reflecting cardiac, liver, kidney and thyroid function, as well as medical therapies showed no significant differences between patients with and without pruritus. In the multivariate logistic regression analysis, only NYHA class (p = 0.016, OR 1.55, 95% confidence interval (CI): [1.09; 2.20]) and elevated leukocyte count (p = 0.007, OR 1.11, CI [1.03; 1.21]) remained significantly associated with pruritus in CHF patients. CONCLUSIONS: NYHA class is an independent predictor for pruritus in CHF patients. Besides NYHA class, leukocyte count was also associated with increased pruritus. Pruritus may impair QoL in CHF patients and should thus be included in the assessment of those patients. We suggest that providing best care for CHF patients can be achieved through an interdisciplinary approach of cardiologists and dermatologists and should include a pruritus assessment.

[Heart failure: update of the ESC 2023 guidelines]. / Herzinsuffizienz: Leitlinien-Update der ESC 2023.

The 2023 update of the European Society of Cardiology (ESC) guidelines recommends (class IA) the administration of sodium-glucose transporter 2 inhibitors (SGLT2i) also for patients with heart failure with preserved ejection fraction (HFpEF) and mildly reduced EF (HFmrEF). Thus, SGLT2i are the only medication that should be given to all heart failure patients for improvement of prognosis independent of left ventricular EF. The rapid administration of the fantastic four drugs and their prompt titration after a heart failure decompensation is now included in the guidelines with a class IB recommendation. For patients with reduced EF (HFrEF) or HFmrEF and iron deficiency there is now a class IIa recommendation for intravenous administration of ferric carboxymaltose or ferric derisomaltose.

[Guidelines of the ESC 2021 on heart failure]. / Herzinsuffizienzleitlinien 2021 der ESC.

The new 2021 guidelines of the European Society of Cardiology (ESC) for the diagnosis and treatment of acute and chronic heart failure include a new terminology for heart failure (HF) with a left ventricular ejection fraction (EF) of 41-49%. This group of patients is now defined as HF with mildly reduced EF (HFmrEF; formerly mid-range). For this form of HF there are now for the first time recommendations for treatment with the standard medications, which are also used for HFrEF. Also new is a class I recommendation for the treatment of HFrEF patients with or without diabetes mellitus with sodium-glucose cotransporter 2 inhibitors (SGLT2i). It must be emphasized that all HFrEF patients should be treated with a combination of four drugs consisting of an angiotensin receptor-neprilysin inhibitor (ARNI) or angiotensin-converting enzyme (ACE) inhibitor, beta blocker, mineralocorticoid receptor antagonist (MRA) and SGLT2i. The primary treatment with ARNI can also be considered without the previous use of an ACE inhibitor. Primary prophylactic implantation of an implantable cardioverter defibrillator (ICD) continues to be a class I indication for patients with an EF of 35% or less in cases of ischemic cardiomyopathy; however, in cases of a non-ischemic cause there is a class IIa indication. This article summarizes these and further important novelties of the 2021 ESC guidelines taking the underlying clinical studies into account.

Phenomic and genomic approaches to studying the inhibition of multiresistant Salmonella enterica by microcin J25.

In livestock production, antibiotics are used to promote animal growth, control infections and thereby increase profitability. This practice has led to the emergence of multiresistant bacteria such as Salmonella, of which some serovars are disseminated in the environment. The objective of this study is to evaluate microcin J25 as an inhibitor of Salmonella enterica serovars of various origins including human, livestock and food. Among the 116 isolates tested, 37 (31.8%) were found resistant to at least one antibiotic, and 28 were multiresistant with 19 expressing the penta-resistant phenotype ACSSuT. Microcin J25 inhibited all isolates, with minimal inhibitory concentration values ranging from 0.06 µg/ml (28.4 nM) to 400 µg/ml (189 µM). Interestingly, no cross-resistance was found between microcin J25 and antibiotics. Multiple sequence alignments of genes encoding for the different proteins involved in the recognition and transport of microcin J25 showed that only ferric-hydroxamate uptake is an essential determinant for susceptibility of S. enterica to microcin J25. Examination of Salmonella strains exposed to microcin J25 by transmission electronic microscopy showed for the first-time involvement of a pore formation mechanism. Microcin J25 was a strong inhibitor of several multiresistant isolates of Salmonella and may have a great potential as an alternative to antibiotics.

The effect of Si/Al ratio of ZSM-12 zeolite on its morphology, acidity and crystal size for the catalytic performance in the HTO process.

In this research, ZSM-12 zeolite with six Si/Al ratios (20 to 320) was synthesized by a hydrothermal method and systematically investigated. The physicochemical properties of the synthesized nano zeolites were evaluated and compared by XRD, FE-SEM,ICP-AES, NH3-TPD, BET, FT-IR, and TGA analyses. The results show that when the Si/Al ratio increases, the amount of microcrystals increases with the dominant competitive phase of cristobalite by decreasing the MTW phase. The catalytic assessment of synthesized zeolites in the (n-hexane to olefins) HTO process in a fixed bed reactor under atmospheric pressure and WHSV equal to 4 h-1 at 550 °C was evaluated and various parameters such as selectivity towards light olefins, P/E ratio, production of light alkanes, and aromatic compounds (BTX) were investigated. The result of the n-hexane to olefins process indicated that the presence of cristobalite as an impurity phase strongly affects the activity of the catalysts. The Z80 zeolite, with a Si/Al ratio of 80, corresponds to the pure form of ZSM-12 and exhibits the highest light olefin yield at 52.5%. This zeolite demonstrates superior propylene selectivity (P/E = 1.75) owing to its well-suited pore structure, wide channels, and optimal acidity derived from the MTW zeolite. On the other hand, zeolite Z320 has a lower light olefin yield (19.4%) and a lower P/E (1.1) ratio. In addition, according to the results of the TGA analysis, the content of coke on the Z80 catalyst after the catalytic reaction is much less than other catalysts after the catalytic reactor test.

A practical approach to the guideline-directed pharmacological treatment of heart failure with reduced ejection fraction.

Over the last 15-20 years, remarkable developments of heart failure (HF) pharmacotherapies have been achieved. However, HF remains a global healthcare challenge with more than 64 million patients worldwide. Optimization of guideline-directed chronic HF medical therapy is highly recommended with every patient visit to improve outcomes in patients with HF with reduced ejection fraction. However, the majority of patients in real-world settings are treated with doses that are lower than those with proven efficacy in clinical trials, which might be due to concerns of adverse effects and inertia of physicians. Likewise, a significant proportion of patients still do not receive all drug classes that could improve their prognosis. The recent European Society of Cardiology guidelines do not provide detailed recommendations on how these drug classes should be implemented in the treatment of inpatients to allow for both safety and a high likelihood of efficacy. We therefore propose a practical approach algorithm to support physicians to treat HF patients in their daily practice.

Targeting Enterococci with Antimicrobial Activity against Clostridium perfringens from Poultry.

Necrotic enteritis (NE), caused by Clostridium perfringens, is an emerging issue in poultry farming. New approaches, other than antibiotics, are necessary to prevent NE development and the emergence of multidrug-resistant bacteria. Enterococci are commensal microorganisms that can produce enterocins, antimicrobial peptides with activities against pathogens, and could be excellent candidates for protective cultures. This study aimed to screen and characterize Enterococcus strains of poultry origin for their inhibitory activity against C. perfringens. In total, 251 Enterococcus strains of poultry origin plus five bacteriocin-producing (BP+) E. durans strains of other origins were screened for antimicrobial activity against the indicator C. perfringens X2967 strain using the "spot on the lawn" method. We detected thirty-two BP+ strains (eleven Enterococcus faecium, nine E. gallinarum, eight E. faecalis, three E. durans, and one E. casseliflavus). We further studied the antimicrobial activity of the supernatants of these 32 BP+ strains using agar well diffusion and microtitration against a collection of 20 C. perfringens strains. Twelve BP+ enterococci that were found to exhibit antimicrobial activity against C. perfringens were characterized using whole genome sequencing. Among these, E. faecium X2893 and X2906 were the most promising candidates for further studies as protective cultures for poultry farming. Both strains belong to the sequence type ST722, harbor the genes encoding for enterocin A and enterocin B, do not possess acquired resistance genes, do not carry plasmids, and present the acm gene, which is implicated in host colonization. Further research is needed to determine the utility of these strains as protective cultures.

[Raw meat, lots of problems: rare infection in a patient after mechanical valve replacement and liver transplantation]. / Rohes Fleisch, viele Probleme: seltene Infektion bei einem Patienten nach mechanischem Klappenersatz und Lebertransplantation.

We report about a 43-year-old man who presented to the emergency department in septic shock with nonspecific gastrointestinal symptoms. Sonography and computed tomography (CT) could not identify the location of the infection in the patient who had undergone liver transplantation and has a mechanical mitral valve. Blood cultures were positive for Listeria monocytogenes. Transesophageal echocardiography showed prosthetic endocarditis. The findings regressed markedly under ampicillin.

Bacteriocin-Based Synergetic Consortia: a Promising Strategy to Enhance Antimicrobial Activity and Broaden the Spectrum of Inhibition.

Bacteria-derived natural antimicrobial compounds such as bacteriocins, reruterin, and organic acids have recently received substantial attention as food preservatives or therapeutic alternatives in human or animal sectors. This study aimed to evaluate the antimicrobial activity of different bacteria-derived antimicrobials, alone or in combination, against a large panel of Gram-negative and Gram-positive bacteria. Bacteriocins, including microcin J25, pediocin PA-1, nisin Z, and reuterin, were investigated alone or in combination with lactic acid and citric acid, using a checkerboard assay. Concentrations were selected based on predetermined MICs against Salmonella enterica subsp. enterica serovar Newport ATCC 6962 and Listeria ivanovii HPB28 as Gram-negative and Gram-positive indicator strains, respectively. The results demonstrated that the combination of microcin J25 + citric acid + lactic acid; microcin J25 + reuterin + citric acid; and microcin J25 + reuterin + lactic acid tested against S. Newport ATCC 6962 showed synergistic effects (FIC index = 0.5). Moreover, a combination of pediocin PA-1 + citric acid + lactic acid; and reuterin + citric acid + lactic acid against L. ivanovii HPB28 showed a partially synergistic interactions (FIC index = 0.75). Nisin Z exerted a partially synergistic effect in combination with acids (FIC index = 0.625 -0.75), whereas when it was combined with reuterin or pediocin PA-1, it showed additive effects (FIC index = 1) against L. ivanovii HPB28. The inhibitory activity of synergetic consortia were tested against a large panel of Gram-positive and Gram-negative bacteria. According to our results, combining different antimicrobials with different mechanisms of action led to higher potency and a broad spectrum of inhibition, including multidrug-resistance pathogens. IMPORTANCE Reuterin and bacteriocins, including microcin J25, pediocin PA-1, nisin were produced and purified with >90% purity. Using the broth-based checkerboard assay the interaction between these compounds (synergetic, additive, or antagonistic) was assessed. By combining different natural antimicrobials with different modes of action and structure (reuteirn, microcin J25, pediocin PA-1, and organic acids), we successfully developed five different synergetic consortia with improved antimicrobial activity and a broad spectrum of inhibition. These consortia were shown to be effective against a large panel of pathogenic and spoilage microorganisms as well as clinically important multidrug-resistance bacteria. Moreover, because the lower concentrations of bacteriocins and reuterin are used in the synergetic consortia, there is a limited risk of toxicity and resistance development for these compounds.

Cardiac Rhythm Monitoring Using Wearables for Clinical Guidance before and after Catheter Ablation.

Mobile health technologies are gaining importance in clinical decision-making. With the capability to monitor the patient's heart rhythm, they have the potential to reduce the time to confirm a diagnosis and therefore are useful in patients eligible for screening of atrial fibrillation as well as in patients with symptoms without documented symptom rhythm correlation. Such is crucial to enable an adequate arrhythmia management including the possibility of a catheter ablation. After ablation, wearables can help to search for recurrences, in symptomatic as well as in asymptomatic patients. Furthermore, those devices can be used to search for concomitant arrhythmias and have the potential to help improving the short- and long-term patient management. The type of wearable as well as the adequate technology has to be chosen carefully for every situation and every individual patient, keeping different aspects in mind. This review aims to describe and to elaborate a potential workflow for the role of wearables for cardiac rhythm monitoring regarding detection and management of arrhythmias before and after cardiac electrophysiological procedures.

[A practical approach to guideline-directed pharmacological treatment for heart failure with reduced ejection fraction]. / Frühe Implementierung der "Fantastic four" bei Herzinsuffizienz mit reduzierter Ejektionsfraktion.

The 2021 guidelines of the European Society of Cardiology for the diagnosis and treatment of heart failure recommend the early implementation of all four mortality-lowering drug classes for heart failure with reduced ejection fraction (HFrEF), i. e. angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor II blocker-neprilysin inhibitor (ARNI), betablocker (BB), mineralocorticoid receptor-antagonists (MRA), and sodium-glucose linked transporter-2 inhibitors (SGLT2i). This article aims to give a practical compendium supporting physicians to enable safe and efficacious treatment for patients with HFrEF.

Malignant External Otitis in a Patient With Diabetes Mellitus: Comparison of Bone Scan SPECT/CT and 68Ga-Citrate PET/CT.

ABSTRACT: We reported a 66-year-old woman with malignant external otitis who was referred to our department for evaluation of disease extension. Both 99mTc-MDP bone SPECT/CT and 68Ga-citrate PET/CT were done for the patient. Both studies showed concordant areas of increased uptake in the petrous bone. In addition, 68Ga-citrate PET/CT showed soft tissue infection in the nasopharyngeal wall. Our case showed the potential of 68Ga-citrate PET/CT for evaluation of malignant external otitis.

In vitro assessment of skin sensitization, irritability and toxicity of bacteriocins and reuterin for possible topical applications.

Bacteriocins and reuterin are promising antimicrobials for application in food, veterinary, and medical sectors. In the light of their high potential for application in hand sanitizer, we investigated the skin toxicity of reuterin, microcin J25, pediocin PA-1, bactofencin A, and nisin Z in vitro using neutral red and LDH release assays on NHEK cells. We determined their skin sensitization potential using the human cell line activation test (h-CLAT). Their skin irritation potential was measured on human epidermal model EpiDerm™. We showed that the viability and membrane integrity of NHEK cells remained unaltered after exposure to bacteriocins and reuterin at concentrations up to 400 µg/mL and 80 mg/mL, respectively. Furthermore, microcin J25 and reuterin showed no skin sensitization at concentrations up to 100 µg/mL and 40 mg/mL, respectively, while pediocin PA-1, bactofencin A, and nisin Z caused sensitization at concentrations higher than 100 µg/mL. Tissue viability was unaffected in presence of bacteriocins and reuterin at concentrations up to 200 µg/mL and 40 mg/mL, respectively, which was confirmed by measuring cytokine IL-1α and IL-8 levels and by histological analysis. In conclusion, the current study provides scientific evidence that some bacteriocins and reuterin, could be safely applied topically as sanitizers at recommended concentrations.

Multicomponent reactions of ammonium thiocyanate, acyl chlorides, alkyl bromides, and enaminones: a facile one-pot synthesis of thiophenes.

An efficient synthesis of thiophene derivatives is described via one-pot reaction between ammonium thiocyanate, acyl chlorides, α-halocarbonyls, and enaminones under solvent-free conditions at 65 °C. The mild reaction conditions and high yields of the products exhibit the good synthetic advantage of these methods.

Bacteriocins as a new generation of antimicrobials: toxicity aspects and regulations.

In recent decades, bacteriocins have received substantial attention as antimicrobial compounds. Although bacteriocins have been predominantly exploited as food preservatives, they are now receiving increased attention as potential clinical antimicrobials and as possible immune-modulating agents. Infections caused by antibiotic-resistant bacteria have been declared as a global threat to public health. Bacteriocins represent a potential solution to this worldwide threat due to their broad- or narrow-spectrum activity against antibiotic-resistant bacteria. Notably, despite their role in food safety as natural alternatives to chemical preservatives, nisin remains the only bacteriocin legally approved by regulatory agencies as a food preservative. Moreover, insufficient data on the safety and toxicity of bacteriocins represent a barrier against the more widespread use of bacteriocins by the food and medical industry. Here, we focus on the most recent trends relating to the application of bacteriocins, their toxicity and impacts.

Gastrointestinal Stability and Cytotoxicity of Bacteriocins From Gram-Positive and Gram-Negative Bacteria: A Comparative in vitro Study.

Bacteriocins are receiving increased attention as potent candidates in food preservation and medicine. Although the inhibitory activity of bacteriocins has been studied widely, little is known about their gastrointestinal stability and toxicity toward normal human cell lines. The aim of this study was to evaluate the gastrointestinal stability and activity of microcin J25, pediocin PA-1, bactofencin A and nisin using in vitro models. In addition cytotoxicity and hemolytic activity of these bacteriocins were investigated on human epithelial colorectal adenocarcinoma cells (Caco-2) and rat erythrocytes, respectively. Pediocin PA-1, bactofencin A, and nisin were observed to lose their stability while passing through the gastrointestinal tract, while microcin J25 is only partially degraded. Besides, selected bacteriocins were not toxic to Caco-2 cells, and integrity of cell membrane was observed to remain unaffected in presence of these bacteriocins at concentrations up to 400 µg/mL. In hemolysis study, pediocin PA-1, bactofencin A, and nisin were observed to lyse rat erythrocytes at concentrations higher than 50 µg/mL, while microcin J25 showed no effect on these cells. According to data indicating gastrointestinal degradation and the absence of toxicity of pediocin PA-1, bactofencin A, and microcin J25 they could potentially be used in food or clinical applications.

In vitro investigation of gastrointestinal stability and toxicity of 3-hyrdoxypropionaldehyde (reuterin) produced by Lactobacillus reuteri.

Reuterin (3-hyrdoxypropionaldehyde (3-HPA)) is a highly potent metabolite of L. reuteri, which has applications in food, health, and veterinary sectors. Similar to other natural antimicrobial compounds, the approval of reuterin as a bio-preservative or therapeutic agent by regulatory agencies relies on sufficient data on its cytotoxicity and behavior in the gastrointestinal environment. Although the antimicrobial activity of reuterin has been broadly studied, its safety and toxicity are yet to be explored in detail. In this study, the stability and activity of reuterin were investigated in the gastrointestinal tract using in vitro models simulating gastrointestinal conditions. In addition, hemolytic activity and in vitro cytotoxicity of reuterin were evaluated by neutral red assay and lactate dehydrogenase (LDH) colorimetric assay using the same cell line. Activity of reuterin was observed to be stable during gastrointestinal transit. Viability and membrane integrity of cells remained unaltered by reuterin up to 1080 mM concentration. Furthermore, no hemolysis was observed in blood cells exposed to 270 mM reuterin. This study provides unique and highly relevant in vitro data regarding gastrointestinal behavior and toxicity of reuterin. In conclusion, the current study indicates that within a certain concentration range, reuterin can be safely used in bio-preservation and therapeutics applications. However, further in vivo studies are required to confirm these findings.

Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.