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ABSTRACT Third-generation cephalosporin-resistant Enterobacterales is a major threat for newborns in neonatal intensive care units (NICUs). The route of acquisition in a non-outbreak setting should be investigated to implement adequate infection prevention measures. To identify risk factors for colonization with and to investigate the transmission pattern of third-generation cephalosporin-resistant Enterobacterales in a NICU setting. This monocentric observational cohort study in a tertiary NICU in Heidelberg, Germany, enrolled all hospitalized neonates screened for cephalosporin-resistant Enterobacterales. Data were collected from 1 January 2018 to 31 December 2021. Weekly screening by rectal swabs for colonization with third-generation cephalosporin-resistant Enterobacterales was performed for all newborns until discharge. Whole-genome sequencing was performed for molecular characterization and transmission analysis. In total, 1,287 newborns were enrolled. The median length of stay was 20 (range 1–250) days. Eighy-eight infants (6.8%) were colonized with third-generation cephalosporin-resistant Enterobacterales. Low birth weight [

For almost nearly a century, memory functions have been attributed only to acquired immune cells. Lately, this paradigm has been challenged by an increasing number of studies revealing that innate immune cells are capable of exhibiting memory-like features resulting in increased responsiveness to subsequent challenges, a process known as trained immunity (known also as innate memory). In contrast, the refractory state of endotoxin tolerance has been defined as an immunosuppressive state of myeloid cells portrayed by a significant reduction in the inflammatory capacity. Both training as well tolerance as adaptive features are reported to be accompanied by epigenetic and metabolic alterations occurring in cells. While training conveys proper protection against secondary infections, the induction of endotoxin tolerance promotes repairing mechanisms in the cells. Consequently, the inappropriate induction of these adaptive cues may trigger maladaptive effects, promoting an increased susceptibility to secondary infections—tolerance, or contribute to the progression of the inflammatory disorder—trained immunity. This review aims at the discussion of these opposing manners of innate immune and non-immune cells, describing the molecular, metabolic and epigenetic mechanisms involved and interpreting the clinical implications in various inflammatory pathologies.

Neutrophils are classically characterized as merely reactive innate effector cells. However, the microbiome is known to shape the education and maturation process of neutrophils, improving their function and immune-plasticity. Recent reports demonstrate that murine neutrophils possess the ability to exert adaptive responses after exposure to bacterial components such as LPS (Gram-negative bacteria) or LTA (Gram-positive bacteria). We now ask whether small extracellular vesicles (EVs) from the gut may directly mediate adaptive responses in neutrophils in vitro. Murine bone marrow-derived neutrophils were primed in vitro by small EVs of high purity collected from colon stool samples, followed by a second hit with LPS. We found that low-dose priming with gut microbiota-derived small EVs enhanced pro-inflammatory sensitivity as indicated by elevated levels of TNF-α, IL-6, ROS and MCP-1 and increased migratory and phagocytic activity. In contrast, high-dose priming resulted in a tolerant phenotype, marked by increased IL-10 and decreased transmigration and phagocytosis. Alterations in TLR2/MyD88 as well as TLR4/MyD88 signaling were correlated with the induction of adaptive cues in neutrophils in vitro. Taken together, our study shows that small EVs from stools can drive adaptive responses in neutrophils in vitro and may represent a missing link in the gut–immune axis.

A growing body of evidence suggests that innate immune cells can respond in a memory-like (adaptive) fashion, which is referred to as trained immunity. Only few in vivo studies have shown training effects in neutrophils; however, no in vitro setup has been established to study the induction of trained immunity or tolerance in neutrophils by microbial agents. In light of their short lifespan (up to 48 h), we suggest to use the term trained sensitivity for neutrophils in an in vitro setting. Here, we firstly describe a feasible two-hit model, using different doses of lipopolysaccharide (LPS) in bone marrow neutrophils. We found that low doses (10 pg/mL) induce pro-inflammatory activation (trained sensitivity), whereas priming with high doses (100 ng/mL) leads to suppression of pro-inflammatory mediators such as TNF-α or IL-6 (tolerance) (p < 0.05). On a functional level, trained neutrophils displayed increased phagocytic activity and LFA-1 expression as well as migrational capacity and CD11a expression, whereas tolerant neutrophils show contrasting effects in vitro. Mechanistically, TLR4/MyD88/PI3Ks regulate the activation of p65, which controls memory-like responses in mouse bone marrow neutrophils (p < 0.05). Our results open a new window for further in vitro studies on memory-like inflammatory responses of short-lived innate immune cells such as neutrophils.

Catheter-directed intervention to treat atrial fibrillation (AF) is becoming widely accepted procedure in current clinical practice. For assessment of pulmonary vein (PV) anatomy, angiography of left atrium (LA) and/or PV is often performed. We present a new, simple angiographic method for PVs and LA opacification using SL1 sheath. Total of 100 patients in our clinic underwent this procedure. In all of the cases good angiographic results were achieved. No immediate or late complications related to this procedure were observed.

Normally, horse urine is light-dark yellow and can be thread-like due to its high mucin content. The physiological pH value is 7–9, the urine specific gravity is 1.020–1.050 g/ml. The macroscopic examination of the urine provides important information. Dependent on the amount of fluid intake the colour of urine can range from almost colourless to dark brown discoloration. Furthermore, the colour depends on the substances that are excreted with the urine. The presence of blood in the urine is pathological and called haematuria. In this case, the urine is so heavily contaminated with blood that even blood clots can be excreted. However, if the urine is only reddish in colour, haematuria must be distinguished from haemoglobinuria or myoglobinuria. To differentiate it macroscopically alone can be difficult so that horse owners may wrongly report that their horse has passed bloody urine. The occurrence of haematuria involves a wide range of differential diagnoses that must be systematically clarified. It is essential to differentiate between systemic diseases and those of the urinary system. In the first place a general examination should be carried out. Then it should be followed by a hematological examination and an analysis of the urine. If the urine is collected spontaneously, the midstream urine is most suitable for further investigations, as contaminations have been flushed out before collection. If these investigations result that there is a disease of the urinary tract, transrectal palpation and transrectal and transabdominal sonographic examination should also be performed. Further diagnostic procedures such as urethroscopy and cystoscopy are also indicated. In the following case report, a twenty-three-year-old Oldenburg gelding with macrohematuria was presented. Cystoscopy revealed a mass whose surface was uneven, rough and partly covered with fibrin and blood clots. A transendoscopic biopsy was requested. Depending on the consistency and location of the growth, sampling may be difficult. A temporary perineal urethrotomy facilitates biopsy collection while providing the opportunity for direct visualization of the urinary bladder contents. Perineal urethrotomy is a well-known method in male patients with obstructive urinary tract disease for temporary diversion of urine. In the following case report, this method was performed to obtain a sufficiently large biopsy specimen using uterine biopsy forceps. The results of the mentioned examinations resulted in the diagnosis of a transitional cell carcinoma (TCC) in the urinary bladder. Primary bladder tumors are very rare in horses and often produce a reactive inflammatory change. The urinary tract is lined with transitional cell epithelium, so transitional cell carcinoma can occur in any section, but most commonly in the bladder wall in horses. It must be clarified whether there are already metastases. Depending on the stage, spread and size of this malignant tumour, therapy can be considered. Surgical removal of a bladder tumour in horses is difficult due to the anatomical location of the urinary bladder in the abdominal cavity and the tendency of these tumors to invade the bladder wall. However, various therapeutic approaches have been described in the literature. Authors report chemotherapy, irradiation with a diode laser or surgical ablation of the cancerous tissue and oral application of piroxicam. Pronounced clinical symptoms are only seen at an advanced stage of the tumour, so that the disease is diagnosed mostly too late for a curative approach. However, early diagnosis is crucial for the prognosis and therefore a detailed diagnostic investigation is required in the case of microhaematuria. Because of the late stage of the disease and the poor prognosis the patient of the current report was euthanized. [ABSTRACT FROM AUTHOR]