Complications related to short peripheral intravenous catheters in patients with acute stroke: a prospective, observational, single-cohort study.

Patients with acute stroke often require venous access to facilitate diagnostic investigations or intravenous therapy. The primary aim of this study was to describe the rate and type of complications associated with the placement of a short peripheral catheter (SPC) in patients with acute ischemic or hemorrhagic stroke. A prospective, observational, single-cohort study was conducted at Niguarda Hospital, Italy, with enrolment in the Emergency Department. Adult patients with an ischemic or hemorrhagic stroke requiring an SPC were enrolled. Complications, such as infiltration, occlusion, phlebitis and dislodgment, were recorded daily. Descriptive statistics were used, and the incidence rate ratio (IRR) was estimated to assess the difference in complications, considering catheter calibre, dominant side, exit site, limb, and limb mobility, ictus type (ischemic/haemorrhagic), impairment deficit (language, motor, visual) and EA-DIVA score. A total of 269 participants and 755 SPC were analysed. Removal of SPC due to at least one local complication occurred in 451 (60%). Dislodgment was the major cause of SPC removal (31%), followed by infiltration (18%), occlusion (6%), and phlebitis (5%). The SPC calibre (22G), exit-site other than antecubital and forearm, visual deficit and EA-DIVA ≥ 8 were associated with a higher rate of SPC complications: IRR, 1.71 [1.31; 2.31]; 1.27 [1.01; 1.60], 1.38 [1.06; 1.80], 1.30 [1.04; 1.64], respectively. No other differences in complication rates were observed according to the insertion site, i.e. dominant side, left side, plegic/hyposthenic limb, or exit site. This study provides novel insights into the frequency and types of complications associated with SPC in patients with acute stroke. Compared to the literature, a higher dislodgment rate was observed, being the first cause of SPC removal, whereas no differences in the number of infiltrations, occlusions, and phlebitis were recorded.

Evaluation of Sterify Gel as an Adjunctive Treatment to Scaling and Root Planing in Promoting Healing of Periodontal Pockets: A Split-Mouth Randomized Controlled Trial.

Background: Periodontal disease is a common infectious disease that leads to the destruction of tooth-supporting structures. Current treatments, such as scaling and root planing (SRP), have limitations in deep and complex pockets, and antibiotic use carries the risk of resistance. Sterify Gel, a medical device composed of polyvinyl polymers, hydroxytyrosol, nisin, and magnesium ascorbyl phosphate, offers a new approach to periodontal care. This study aims to evaluate the safety and efficacy of Sterify Gel as an adjunctive treatment to SRP in promoting the healing of periodontal pockets. Methods: The study includes 34 patients with moderate to advanced chronic periodontal disease. Randomization assigned one site for SRP alone (control) and the other site for SRP with Sterify Gel (treatment). Periodontal parameters were evaluated at baseline, 1, 2, and 3 months after treatment bacterial contamination was assessed through quantitative PCR at baseline and 3 months after treatment. Statistical analysis was conducted using ANOVA and Wilcoxon test. Results: Treatment with Sterify Gel and SRP demonstrated significant improvements in pocket depth, gingival recession, and clinical attachment level compared with SRP alone. Bleeding and plaque indexes, pain perception, tooth mobility, and furcations showed no significant differences between the two groups. The treatment group showed a reduction in bacterial contamination at 3 months. Conclusions: Sterify Gel in combination with SRP shows the potential for improving periodontal health by promoting healing and reducing periodontal pockets. It may offer benefits in preventing bacterial recolonization and reducing reliance on antibiotics.

Can the length of a catheter change the time to bubble at the tip performing the "Bubble Test"? A bench study.

INTRODUCTION: Intraprocedural tip control techniques are critical during central venous catheter placement. According to international guidelines (INS 2021), intracavitary electrocardiography is the first method of choice to verify it; when this technique is not feasible, it is considered acceptable to use a contrast-enhanced ultrasound-based tip location method, commonly known as "bubble-test" as an effective alternative. OBJECTIVE: To assess whether the length of the vascular catheter can alter the time between the injection of the contrast media and its appearance at the catheter tip and the injection duration. Differences between operators stratified according to experience were evaluated as secondary endpoints. METHODS: A bench study was conducted using an extracorporeal circuit. For each catheter length (60, 40, and 20 cm), three injections were obtained by each of the five operators with different levels of experience for a total of 45 measurements. Differences among operators were evaluated using ANOVA, and the impact of catheter length and operator expertise on times was assessed using repeated measurement models. RESULTS: Hub-to-tip times of 247.33 ms (SD 168.82), 166 ms (SD 95.46), 138 ms (SD 54.48), and injection duration of 1620 ms (SD 748.58), 1614 ms (SD 570.95), 1566 ms (SD 302.83) were observed for 60, 40, 20 cm catheter length, respectively. A significant time variability between operators was observed. Moreover, moving from 60 to 20 cm, hub-to-tip time was significantly longer for 60 cm devices (p = 0.0124), while little differences were observed for injection duration. CONCLUSIONS: Catheter length can change both the time between the injection of the contrast media and its appearance at the catheter tip and the injection duration. Hub-to-tip times obtained with 20 and 40 cm and overall injection duration did not differ significantly; skilled personnel could substantially reduce both values analyzed in this study.

Mitochondrial Ca2+ signaling and Alzheimer's disease: Too much or too little?

Alzheimer's disease (AD) is a neurodegenerative disease, caused by poorly known pathogenic mechanisms and aggravated by delayed therapeutic intervention, that still lacks an effective cure. However, it is clear that some important neurophysiological processes are altered years before the onset of clinical symptoms, offering the possibility of identifying biological targets useful for implementation of new therapies. Of note, evidence has been provided suggesting that mitochondria, pivotal organelles in sustaining neuronal energy demand and modulating synaptic activity, are dysfunctional in AD samples. In particular, alterations in mitochondrial Ca2+ signaling have been proposed as causal events for neurodegeneration, although the exact outcomes and molecular mechanisms of these defects, as well as their longitudinal progression, are not always clear. Here, we discuss the importance of a correct mitochondrial Ca2+ handling for neuronal physiology and summarize the latest findings on dysfunctional mitochondrial Ca2+ pathways in AD, analysing possible consequences contributing to the neurodegeneration that characterizes the disease.

Loosening ER-Mitochondria Coupling by the Expression of the Presenilin 2 Loop Domain.

Presenilin 2 (PS2), one of the three proteins in which mutations are linked to familial Alzheimer's disease (FAD), exerts different functions within the cell independently of being part of the γ-secretase complex, thus unrelated to toxic amyloid peptide formation. In particular, its enrichment in endoplasmic reticulum (ER) membrane domains close to mitochondria (i.e., mitochondria-associated membranes, MAM) enables PS2 to modulate multiple processes taking place on these signaling hubs, such as Ca2+ handling and lipid synthesis. Importantly, upregulated MAM function appears to be critical in AD pathogenesis. We previously showed that FAD-PS2 mutants reinforce ER-mitochondria tethering, by interfering with the activity of mitofusin 2, favoring their Ca2+ crosstalk. Here, we deepened the molecular mechanism underlying PS2 activity on ER-mitochondria tethering, identifying its protein loop as an essential domain to mediate the reinforced ER-mitochondria connection in FAD-PS2 models. Moreover, we introduced a novel tool, the PS2 loop domain targeted to the outer mitochondrial membrane, Mit-PS2-LOOP, that is able to counteract the activity of FAD-PS2 on organelle tethering, which possibly helps in recovering the FAD-PS2-associated cellular alterations linked to an increased organelle coupling.

Better to keep in touch: investigating inter-organelle cross-talk.

The strategic importance for cellular organelles of being in contact with each other, exchanging messenger molecules, is nowadays well established. Different inter-organelle cross-talk pathways finely regulate multiple physiological cellular mechanisms, and their dysregulation has been found to underlie different pathological conditions. In the last years, a great effort has been made to study such organelle interactions, to understand their functional roles within the cell and the molecules involved in their formation and/or modulation. In this contribution, some examples of organelle cross-talk and their contributions in regulating physiological processes are presented. Moreover, the pro and cons of the available methods for a proper, reliable investigation of membrane contact sites are described.

Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks.

Presenilin-2 (PS2) is one of the three proteins that are dominantly mutated in familial Alzheimer's disease (FAD). It forms the catalytic core of the γ-secretase complex-a function shared with its homolog presenilin-1 (PS1)-the enzyme ultimately responsible of amyloid-ß (Aß) formation. Besides its enzymatic activity, PS2 is a multifunctional protein, being specifically involved, independently of γ-secretase activity, in the modulation of several cellular processes, such as Ca2+ signalling, mitochondrial function, inter-organelle communication, and autophagy. As for the former, evidence has accumulated that supports the involvement of PS2 at different levels, ranging from organelle Ca2+ handling to Ca2+ entry through plasma membrane channels. Thus FAD-linked PS2 mutations impact on multiple aspects of cell and tissue physiology, including bioenergetics and brain network excitability. In this contribution, we summarize the main findings on PS2, primarily as a modulator of Ca2+ homeostasis, with particular emphasis on the role of its mutations in the pathogenesis of FAD. Identification of cell pathways and molecules that are specifically targeted by PS2 mutants, as well as of common targets shared with PS1 mutants, will be fundamental to disentangle the complexity of memory loss and brain degeneration that occurs in Alzheimer's disease (AD).

Sarcoplasmic Reticulum-Mitochondria Kissing in Cardiomyocytes: Ca2+, ATP, and Undisclosed Secrets.

In cardiomyocytes, to carry out cell contraction, the distribution, morphology, and dynamic interaction of different cellular organelles are tightly regulated. For instance, the repetitive close apposition between junctional sarcoplasmic reticulum (jSR) and specialized sarcolemma invaginations, called transverse-tubules (TTs), is essential for an efficient excitation-contraction coupling (ECC). Upon an action potential, Ca2+ microdomains, generated in synchrony at the interface between TTs and jSR, underlie the prompt increase in cytosolic Ca2+ concentration, ultimately responsible for cell contraction during systole. This process requires a considerable amount of energy and the active participation of mitochondria, which encompass ∼30% of the cell volume and represent the major source of ATP in the heart. Importantly, in adult cardiomyocytes, mitochondria are distributed in a highly orderly fashion and strategically juxtaposed with SR. By taking advantage of the vicinity to Ca2+ releasing sites, they take up Ca2+ and modulate ATP synthesis according to the specific cardiac workload. Interestingly, with respect to SR, a biased, polarized positioning of mitochondrial Ca2+ uptake/efflux machineries has been reported, hinting the importance of a strictly regulated mitochondrial Ca2+ handling for heart activity. This notion, however, has been questioned by the observation that, in some mouse models, the deficiency of specific molecules, modulating mitochondrial Ca2+ dynamics, triggers non-obvious cardiac phenotypes. This review will briefly summarize the physiological significance of SR-mitochondria apposition in cardiomyocytes, as well as the pathological consequences of an altered organelle communication, focusing on Ca2+ signaling. We will discuss ongoing debates and propose future research directions.