Immunotherapy with an antibody against CD1d modulates neuroinflammation in an α-synuclein transgenic model of Lewy body like disease.

The neuroinflammatory process in synucleinopathies of the aging population such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB) involves microglial activation as well as infiltration of the CNS by T cells and natural killer T cells (NKTs). To evaluate the potential of targeting NKT cells to modulate neuroinflammation, we treated α-syn transgenic (tg) mice (e.g.: Thy1 promoter line 61) with an antibody against CD1d, which is a glycoprotein expressed in antigen presenting cells (APCs). CD1d-presented lipid antigens activate NKT cells through the interaction with T cell receptor in NKTs, resulting in the production of cytokines. Thus, we hypothesized that blocking the APC-NKT interaction with an anti-CD1d antibody might reduce neuroinflammation and neurodegeneration in models of DLB/PD. Treatment with the anti-CD1d antibody did not have effects on CD3 (T cells), slightly decreased CD4 and increased CD8 lymphocytes in the mice. Moreover, double labeling studies showed that compared to control (IgG) treated α-syn tg mice, treatment with anti-CD1d decreased numbers of CD3/interferon γ (IFN γ)-positive cells, consistent with NKTs. Further double labeling studies showed that CD1d-positive cells co-localized with the astrocytes marker GFAP and that anti-CD1d antibody reduced this effect. While in control α-syn tg mice CD3 positive cells were near astrocytes, this was modified by the treatment with the CD1d antibody. By qPCR, levels of IFN γ, CCL4, and interleukin-6 were increased in the IgG treated α-syn tg mice. Treatment with CD1d antibody blunted this cytokine response that was associated with reduced astrocytosis and microgliosis in the CNS of the α-syn tg mice treated with CD1d antibody. Flow cytometric analysis of immune cells in α-syn tg mice revealed that CD1d-tet + T cells were also increased in the spleen of α-syn tg mice, which treatment with the CD1d antibody reduced. Reduced neuroinflammation in the anti-CD1d-treated α-syn tg mice was associated with amelioration of neurodegenerative pathology. These results suggest that reducing infiltration of NKT cells with an antibody against CD1d might be a potential therapeutical approach for DLB/PD.

[Use of thoracic and lung ultrasound in general anesthesia]. / A mellkas és a tüdo ultrahangvizsgálatának szerepe az általános érzéstelenítés során.

The use of ultrasound became an essential tool in the everyday practice of anesthesiology and intensive care as an indispensable prerequisite for the precise guidance of invasive procedures and also as a point-of-care diagnostic method. Despite the limitations of imaging the lung and thoracic structures, the COVID-19 pandemic and recent advances made this technology an evolving field. The intensive therapy applies these methods with important experience for differential diagnosis and assessment of disease severity or prognosis. Minor modifications of these results make the method beneficial for anesthesia and perioperative medicine. In the present review, the authors accentuate the most important imaging artefacts of lung ultrasonography and the principles of lung ultrasound diagnostic steps. Methods and artefacts of high importance supported by evidence for the assessment of airway management, attuning of intraoperative mechanical ventilation, respiratory disorders during surgery, and postoperative prognosis are articulated. This review intends to focus on evolving subfields in which technological or scientific novelties are expected. Orv Hetil. 2023; 164(22): 864-870.

A preoperative ultrasound-based protocol for optimisation of fluid therapy to prevent early intraoperative hypotension: a randomised controlled study.

BACKGROUND: Intraoperative hypotension is a risk factor for postoperative complications. Preoperative dehydration is a major contributor, although it is difficult to estimate its severity. Point-of-care ultrasound offers several potential methods, including measurements of the inferior vena cava. The addition of lung ultrasound may offer a safety limit. We aimed to evaluate whether the implication of an ultrasound-based preoperative fluid therapy protocol can decrease the incidence of early intraoperative hypotension. METHODS: Randomised controlled study in a tertiary university department involves elective surgical patients of ASA 2-3 class, scheduled for elective major abdominal surgery under general anaesthesia with intubation. We randomised 40-40 patients; 38-38 were available for analysis. Conventional fluid therapy was ordered on routine preoperative visits. Ultrasound-based protocol evaluated the collapsibility index of inferior vena cava and lung ultrasound profiles. Scans were performed twice: 2 h and 30 min before surgery. A high collapsibility index (≥ 40%) indicated a standardised fluid bolus, while the anterior B-profile of the lung ultrasound contraindicated further fluid. The primary outcome was the incidence of postinduction and early intraoperative (0-10 min) hypotension (MAP < 65 mmHg and/or ≥ 30% of decrease from baseline). Secondary endpoints were postoperative lactate level, urine output and lung ultrasound score at 24 h. RESULTS: The absolute criterion of postinduction hypotension was fulfilled in 12 patients in the conventional group (31.6%) and 3 in the ultrasound-based group (7.9%) (p = 0.0246). Based on composite criteria of absolute and/or relative hypotension, we observed 17 (44.7%) and 7 (18.4%) cases, respectively (p = 0.0136). The incidence of early intraoperative hypotension was also lower: HR for absolute hypotension was 2.10 (95% CI 1.00-4.42) in the conventional group (p = 0.0387). Secondary outcome measures were similar in the study groups. CONCLUSION: We implemented a safe and effective point-of-care ultrasound-based preoperative fluid replacement protocol into perioperative care. TRIAL REGISTRATION: The study was registered to ClinicalTrials.gov on 10/12/2021, registration number: NCT05171608 (registered prospectively on 10/12/2021).

Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD.

Alterations in the p38 mitogen-activated protein kinases (MAPKs) play an important role in the pathogenesis of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). Activation of the p38α MAPK isoform and mislocalization of the p38γ MAPK isoform are associated with neuroinflammation and synaptic degeneration in DLB and PD. Therefore, we hypothesized that p38α might be associated with neuronal p38γ distribution and synaptic dysfunction in these diseases. To test this hypothesis, we treated in vitro cellular and in vivo mouse models of DLB/PD with SKF-86002, a compound that attenuates inflammation by inhibiting p38α/ß, and then investigated the effects of this compound on p38γ and neurodegenerative pathology. We found that inhibition of p38α reduced neuroinflammation and ameliorated synaptic, neurodegenerative, and motor behavioral deficits in transgenic mice overexpressing human α-synuclein. Moreover, treatment with SKF-86002 promoted the redistribution of p38γ to synapses and reduced the accumulation of α-synuclein in mice overexpressing human α-synuclein. Supporting the potential value of targeting p38 in DLB/PD, we found that SKF-86002 promoted the redistribution of p38γ in neurons differentiated from iPS cells derived from patients with familial PD (carrying the A53T α-synuclein mutation) and healthy controls. Treatment with SKF-86002 ameliorated α-synuclein-induced neurodegeneration in these neurons only when microglia were pretreated with this compound. However, direct treatment of neurons with SKF-86002 did not affect α-synuclein-induced neurotoxicity, suggesting that SKF-86002 treatment inhibits α-synuclein-induced neurotoxicity mediated by microglia. These findings provide a mechanistic connection between p38α and p38γ as well as a rationale for targeting this pathway in DLB/PD.

Percutaneous tracheostomy: Comparison of three different methods with respect to tracheal cartilage injury in cadavers-Randomized controlled study.

Background: Performing tracheostomy improves patient comfort and success rate of weaning from prolonged invasive mechanical ventilation. Data suggest that patients have more benefit of percutaneous technique than the surgical procedure, however, there is no consensus on the percutaneous method of choice regarding severe complications such as late tracheal stenosis. Aim of this study was comparing incidences of cartilage injury caused by different percutaneous dilatation techniques (PDT), including Single Dilator, Griggs' and modified (bidirectional) Griggs' method. Materials and methods: Randomized observational study was conducted on 150 cadavers underwent post-mortem percutaneous tracheostomy. Data of cadavers including age, gender and time elapsed from death until the intervention (more or less than 72 h) were collected and recorded. Primary and secondary outcomes were: rate of cartilage injury and cannula malposition respectively. Results: Statistical analysis revealed that method of intervention was significantly associated with occurrence of cartilage injury, as comparing either standard Griggs' with Single Dilator (p = 0.002; OR: 4.903; 95% CI: 1.834-13.105) or modified Griggs' with Single Dilator (p < 0.001; OR: 6.559; 95% CI: 2.472-17.404), however, no statistical difference was observed between standard and modified Griggs' techniques (p = 0.583; OR: 0.748; 95% CI: 0.347-1.610). We found no statistical difference in the occurrence of cartilage injury between the early- and late post-mortem group (p = 0.630). Neither gender (p = 0.913), nor age (p = 0.529) influenced the rate of cartilage fracture. There was no statistical difference between the applied PDT techniques regarding the cannula misplacement/malposition. Conclusion: In this cadaver study both standard and modified Griggs' forceps dilatational methods were safer than Single dilator in respect of cartilage injury.

[Role of anthropometric parameters in percutaneous tracheostomies performed on cadavers]. / Az antropometriai paraméterek szerepe a cadaveren végzett percutan tracheostomás módszerekben.

INTRODUCTION AND OBJECTIVE: For patients requiring prolonged mechanical ventilation, tracheostomy becomes necessary, which may be performed through surgical or percutaneous methods. In this study, we used three different methods of percutaneous dilatational tracheostomy. Our goal was to identify anthropometric parameters relevant for the correct position of the tracheostomy tube. MATERIAL AND METHODS: Randomized, controlled observational study was performed on 118 cadavers. Three different tracheostomy methods were used: the Griggs (n = 37), the Griggs modified by Élo (n = 45), and the Ciaglia's Blue Rhino (n = 36). The neck circumference, jugulomental distance, and mid-upper arm circumference were measured on each cadaver. We assessed whether the aforementioned parameters related with the appropriate positioning of the tracheostomy tube Results: Significant correlation was found (p = 0.0287) between mid-upper arm circumference and incorrect tracheostomy tube position (below the fourth tracheal cartilage ring). We identified the value of 30 cm of mid-upper arm circumference as the ideal cut-off for predicting tube malposition (sensitivity: 63.63%, specificity: 60.22%). CONCLUSION: When planning percutaneous tracheostomy, it is important to measure the anthropometric parameters. If mid-upper arm circumference is 30 cm or higher we recommend other tests and/or ENT (ear, nose, and throat) consultation. Orv Hetil. 2023; 164(16): 630-635.

Reliability and clinical correlations of semi-quantitative lung ultrasound on BLUE points in COVID-19 mechanically ventilated patients: The 'BLUE-LUSS'-A feasibility clinical study.

INTRODUCTION: Bedside lung ultrasound has gained a key role in each segment of the treatment chain during the COVID-19 pandemic. During the diagnostic assessment of the critically ill patients in ICUs, it is highly important to maximize the amount and quality of gathered information while minimizing unnecessary interventions (e.g. moving/rotating the patient). Another major factor is to reduce the risk of infection and the workload of the staff. OBJECTIVES: To serve these significant issues we constructed a feasibility study, in which we used a single-operator technique without moving the patient, only assessing the easily achievable lung regions at conventional BLUE points. We hypothesized that calculating this 'BLUE lung ultrasound score' (BLUE-LUSS) is a reasonable clinical tool. Furthermore, we used both longitudinal and transverse scans to measure their reliability and assessed the interobserver variability as well. METHODS: University Intensive Care Unit based, single-center, prospective, observational study was performed on 24 consecutive SARS-CoV2 RT-PCR positive, mechanically ventilated critically ill patients. Altogether 400 loops were recorded, rated and assessed off-line by 4 independent intensive care specialists (each 7+ years of LUS experience). RESULTS: Intraclass correlation values indicated good reliability for transversal and longitudinal qLUSS scores, while we detected excellent interrater agreement of both cLUSS calculation methods. All of our LUS scores correlated inversely and significantly to the P/F values. Best correlation was achieved in the case of longitudinal qLUSS (r = -0.55, p = 0.0119). CONCLUSION: Summarized score of BLUE-LUSS can be an important, easy-to-perform adjunct tool for assessing and quantifying lung pathology in critically ill ventilated patients at bedside, especially for the P/F ratio. The best agreement for the P/F ratio can be achieved with the longitudinal scans. Regarding these findings, assessing BLUE-points can be extended with the BLUE-LUSS for daily routine using both transverse and longitudinal views.

Does SARS-CoV-2 affect neurodegenerative disorders? TLR2, a potential receptor for SARS-CoV-2 in the CNS.

The coronavirus (COVID-19) pandemic, caused by severe acute respiratory system coronavirus 2 (SARS-CoV-2), has created significant challenges for scientists seeking to understand the pathogenic mechanisms of SARS-CoV-2 infection and to identify the best therapies for infected patients. Although ACE2 is a known receptor for the virus and has been shown to mediate viral entry into the lungs, accumulating reports highlight the presence of neurological symptoms resulting from infection. As ACE2 expression is low in the central nervous system (CNS), these neurological symptoms are unlikely to be caused by ACE2-virus binding. In this review, we will discuss a proposed interaction between SARS-CoV-2 and Toll-like receptor 2 (TLR2) in the CNS. TLR2 is an innate immune receptor that recognizes exogenous microbial components but has also been shown to interact with multiple viral components, including the envelope (E) protein of SARS-CoV-2. In addition, TLR2 plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Based on these observations, we hypothesize that TLR2 may play a critical role in the response to SARS-CoV-2 infiltration in the CNS, thereby resulting in the induction or acceleration of AD and PD pathologies in patients.

The Alzheimer's gene SORL1 is a regulator of endosomal traffic and recycling in human neurons.

BACKGROUND: Loss of the Sortilin-related receptor 1 (SORL1) gene seems to act as a causal event for Alzheimer's disease (AD). Recent studies have established that loss of SORL1, as well as mutations in autosomal dominant AD genes APP and PSEN1/2, pathogenically converge by swelling early endosomes, AD's cytopathological hallmark. Acting together with the retromer trafficking complex, SORL1 has been shown to regulate the recycling of the amyloid precursor protein (APP) out of the endosome, contributing to endosomal swelling and to APP misprocessing. We hypothesized that SORL1 plays a broader role in neuronal endosomal recycling and used human induced pluripotent stem cell-derived neurons (hiPSC-Ns) to test this hypothesis. We examined endosomal recycling of three transmembrane proteins linked to AD pathophysiology: APP, the BDNF receptor Tropomyosin-related kinase B (TRKB), and the glutamate receptor subunit AMPA1 (GLUA1). METHODS: We used isogenic hiPSCs engineered to have SORL1 depleted or to have enhanced SORL1 expression. We differentiated neurons from these cell lines and mapped the trafficking of APP, TRKB and GLUA1 within the endosomal network using confocal microscopy. We also performed cell surface recycling and lysosomal degradation assays to assess the functionality of the endosomal network in both SORL1-depleted and -overexpressing neurons. The functional impact of GLUA1 recycling was determined by measuring synaptic activity. Finally, we analyzed alterations in gene expression in SORL1-depleted neurons using RNA sequencing. RESULTS: We find that as with APP, endosomal trafficking of GLUA1 and TRKB is impaired by loss of SORL1. We show that trafficking of all three cargoes to late endosomes and lysosomes is affected by manipulating SORL1 expression. We also show that depletion of SORL1 significantly impacts the endosomal recycling pathway for APP and GLUA1 at the level of the recycling endosome and trafficking to the cell surface. This has a functional effect on neuronal activity as shown by multi-electrode array (MEA). Conversely, increased SORL1 expression enhances endosomal recycling for APP and GLUA1. Our unbiased transcriptomic data further support SORL1's role in endosomal recycling. We observe altered expression networks that regulate cell surface trafficking and neurotrophic signaling in SORL1-depleted neurons. CONCLUSION: Collectively, and together with other recent observations, these findings suggest that one role for SORL1 is to contribute to endosomal degradation and recycling pathways in neurons, a conclusion that has both pathogenic and therapeutic implications for Alzheimer's disease.

Overproduction of hydrogen sulfide, generated by cystathionine ß-synthase, disrupts brain wave patterns and contributes to neurobehavioral dysfunction in a rat model of down syndrome.

Using a novel rat model of Down syndrome (DS), the functional role of the cystathionine-ß-synthase (CBS)/hydrogen sulfide (H2S) pathway was investigated on the pathogenesis of brain wave pattern alterations and neurobehavioral dysfunction. Increased expression of CBS and subsequent overproduction of H2S was observed in the brain of DS rats, with CBS primarily localizing to astrocytes and the vasculature. DS rats exhibited neurobehavioral defects, accompanied by a loss of gamma brain wave activity and a suppression of the expression of multiple pre- and postsynaptic proteins. Aminooxyacetate, a prototypical pharmacological inhibitor of CBS, increased the ability of the DS brain tissue to generate ATP in vitro and reversed the electrophysiological and neurobehavioral alterations in vivo. Thus, the CBS/H2S pathway contributes to the pathogenesis of neurological dysfunction in DS, most likely through dysregulation of cellular bioenergetics and gene expression.

Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies.

Accumulation of misfolded proteins such as amyloid-ß (Aß), tau, and α-synuclein (α-Syn) in the brain leads to synaptic dysfunction, neuronal damage, and the onset of relevant neurodegenerative disorder/s. Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) are characterized by the aberrant accumulation of α-Syn intracytoplasmic Lewy body inclusions and dystrophic Lewy neurites resulting in neurodegeneration associated with inflammation. Cell to cell propagation of α-Syn aggregates is implicated in the progression of PD/DLB, and high concentrations of anti-α-Syn antibodies could inhibit/reduce the spreading of this pathological molecule in the brain. To ensure sufficient therapeutic concentrations of anti-α-Syn antibodies in the periphery and CNS, we developed four α-Syn DNA vaccines based on the universal MultiTEP platform technology designed especially for the elderly with immunosenescence. Here, we are reporting on the efficacy and immunogenicity of these vaccines targeting three B-cell epitopes of hα-Syn aa85-99 (PV-1947D), aa109-126 (PV-1948D), aa126-140 (PV-1949D) separately or simultaneously (PV-1950D) in a mouse model of synucleinopathies mimicking PD/DLB. All vaccines induced high titers of antibodies specific to hα-Syn that significantly reduced PD/DLB-like pathology in hα-Syn D line mice. The most significant reduction of the total and protein kinase resistant hα-Syn, as well as neurodegeneration, were observed in various brain regions of mice vaccinated with PV-1949D and PV-1950D in a sex-dependent manner. Based on these preclinical data, we selected the PV-1950D vaccine for future IND enabling preclinical studies and clinical development.

The role of Alzheimer's disease risk genes in endolysosomal pathways.

There is ample pathological and biological evidence for endo-lysosomal dysfunction in Alzheimer's disease (AD) and emerging genetic studies repeatedly implicate endo-lysosomal genes as associated with increased AD risk. The endo-lysosomal network (ELN) is essential for all cell types of the central nervous system (CNS), yet each unique cell type utilizes cellular trafficking differently (see Fig. 1). Challenges ahead involve defining the role of AD associated genes in the functionality of the endo-lysosomal network (ELN) and understanding how this impacts the cellular dysfunction that occurs in AD. This is critical to the development of new therapeutics that will impact, and potentially reverse, early disease phenotypes. Here we review some early evidence of ELN dysfunction in AD pathogenesis and discuss the role of selected AD-associated risk genes in this pathway. In particular, we review genes that have been replicated in multiple genome-wide association studies(Andrews et al., 2020; Jansen et al., 2019; Kunkle et al., 2019; Lambert et al., 2013; Marioni et al., 2018) and reviewed in(Andrews et al., 2020) that have defined roles in the endo-lysosomal network. These genes include SORL1, an AD risk gene harboring both rare and common variants associated with AD risk and a role in trafficking cargo, including APP, through the ELN; BIN1, a regulator of clathrin-mediated endocytosis whose expression correlates with Tau pathology; CD2AP, an AD risk gene with roles in endosome morphology and recycling; PICALM, a clathrin-binding protein that mediates trafficking between the trans-Golgi network and endosomes; and Ephrin Receptors, a family of receptor tyrosine kinases with AD associations and interactions with other AD risk genes. Finally, we will discuss how human cellular models can elucidate cell-type specific differences in ELN dysfunction in AD and aid in therapeutic development.

The role of ultrasonographic lung aeration score in the prediction of postoperative pulmonary complications: an observational study.

BACKGROUND: Postoperative pulmonary complications (PPCs) are important contributors to mortality and morbidity after surgery. The available predicting models are useful in preoperative risk assessment, but there is a need for validated tools for the early postoperative period as well. Lung ultrasound is becoming popular in intensive and perioperative care and there is a growing interest to evaluate its role in the detection of postoperative pulmonary pathologies. OBJECTIVES: We aimed to identify characteristics with the potential of recognizing patients at risk by comparing the lung ultrasound scores (LUS) of patients with/without PPC in a 24-h postoperative timeframe. METHODS: Observational study at a university clinic. We recruited ASA 2-3 patients undergoing elective major abdominal surgery under general anaesthesia. LUS was assessed preoperatively, and also 1 and 24 h after surgery. Baseline and operative characteristics were also collected. A one-week follow up identified PPC+ and PPC- patients. Significantly differing LUS values underwent ROC analysis. A multi-variate logistic regression analysis with forward stepwise model building was performed to find independent predictors of PPCs. RESULTS: Out of the 77 recruited patients, 67 were included in the study. We evaluated 18 patients in the PPC+ and 49 in the PPC- group. Mean ages were 68.4 ± 10.2 and 66.4 ± 9.6 years, respectively (p = 0.4829). Patients conforming to ASA 3 class were significantly more represented in the PPC+ group (66.7 and 26.5%; p = 0.0026). LUS at baseline and in the postoperative hour were similar in both populations. The median LUS at 0 h was 1.5 (IQR 1-2) and 1 (IQR 0-2; p = 0.4625) in the PPC+ and PPC- groups, respectively. In the first postoperative hour, both groups had a marked increase, resulting in scores of 6.5 (IQR 3-9) and 5 (IQR 3-7; p = 0.1925). However, in the 24th hour, median LUS were significantly higher in the PPC+ group (6; IQR 6-10 vs 3; IQR 2-4; p < 0.0001) and it was an independent risk factor (OR = 2.6448 CI95% 1.5555-4.4971; p = 0.0003). ROC analysis identified the optimal cut-off at 5 points with high sensitivity (0.9444) and good specificity (0.7755). CONCLUSION: Postoperative LUS at 24 h can identify patients at risk of or in an early phase of PPCs.

Depletion of the AD Risk Gene SORL1 Selectively Impairs Neuronal Endosomal Traffic Independent of Amyloidogenic APP Processing.

SORL1/SORLA is a sorting receptor involved in retromer-related endosomal traffic and an Alzheimer's disease (AD) risk gene. Using CRISPR-Cas9, we deplete SORL1 in hiPSCs to ask if loss of SORL1 contributes to AD pathogenesis by endosome dysfunction. SORL1-deficient hiPSC neurons show early endosome enlargement, a hallmark cytopathology of AD. There is no effect of SORL1 depletion on endosome size in hiPSC microglia, suggesting a selective effect on neuronal endosomal trafficking. We validate defects in neuronal endosomal traffic by showing altered localization of amyloid precursor protein (APP) in early endosomes, a site of APP cleavage by the ß-secretase (BACE). Inhibition of BACE does not rescue endosome enlargement in SORL1-deficient neurons, suggesting that this phenotype is independent of amyloidogenic APP processing. Our data, together with recent findings, underscore how sporadic AD pathways regulating endosomal trafficking and autosomal-dominant AD pathways regulating APP cleavage independently converge on the defining cytopathology of AD.

[Implementation of immediate feedback system into hand hygiene practice in the intensive care unit]. / Azonnali visszajelzo rendszer bevezetése a kézhigiéné gyakorlatába intenzív osztályon.

Introduction: Infections affect about 30-50% of intensive care unit patients resulting in substantial morbidity and mortality. Multimodal interventions proved to be successful in the prevention of healthcare-associated infections. Appropriate hand hygiene including correct disinfection technique and timing is essential. Aim: The aim of our study was to investigate the hand hygiene practice among the intensive care unit healthcare workers by immediate feedback system implementation and compliance study. Method: A 3-week-long observational study was conducted at the Department of Anaesthesiology and Intensive Therapy, Semmelweis University, during November and December, 2018. Data regarding hand hygiene technique were collected by using the Semmelweis Scanner technology, while compliance data were recorded by direct observations. Statistical analysis was performed by Kruskal-Wallis test, Fisher's exact test and χ2-test. Results: 604 measurements were recorded by the electronic system. Hand disinfection was appropriate in 86.5% of cases. The median value of coverage was 99.87%. The trend of these indices showed persistently high values. A lower error rate was observed in the physiotherapy group compared to others (doctors: p<0.01, nurses: p = 0.03, assistant nurses: p = 0.03). 162 opportunities were recorded during direct observations. The mean compliance rate was 60.49%, with the lowest among doctors (53.97%). The difference was non-significant compared to nurses (62.92%, p = 0.26). Conclusions: Hand hygiene technique during the study period was found to be highly and permanently appropriate, while compliance was lower than expected. The immediate feedback system may be useful in achieving appropriate hand disinfection technique, although further interventions are needed for higher compliance rates. Orv Hetil. 2019; 160(49): 1957-1962.

Role of inferior vena cava collapsibility index in the prediction of hypotension associated with general anesthesia: an observational study.

BACKGROUND: Intraoperative hypotension increases 30-day mortality and the risks of myocardial injury and acute renal failure. Patients with inadequate volume reserve before the induction of anesthesia are highly exposed. The identification of latent hypovolemia is therefore crucial. Ultrasonographic measurement of the inferior vena cava collapsibility index (IVCCI) is able to detect volume responsiveness in circulatory shock. No current evidence is available regarding whether preoperative measurement of the IVCCI could identify patients at high risk for hypotension associated with general anesthesia. METHODS: A total of 102 patients undergoing elective general surgery under general anesthesia with standardized propofol induction were recruited for this prospective observational study. The IVCCI was measured under spontaneous breathing. A collapsing (IVCCI≧50%) (CI+) and a noncollapsing (CI-) group were formed. Immediate postinduction changes in systolic and mean blood pressure were compared. The performance of the IVCCI as a diagnostic tool for predicting hypotension (systolic pressure < 90 mmHg or a ≥ 30% drop from the baseline) was evaluated by ROC curve analysis. RESULTS: A total of 83 patients were available for analysis, with 20 in the CI+ and 63 in the CI- group, we excluded 19 previously eligible patients due to inadequate visualization of the IVC (7 cases), lack of adherence to the protocol (8 cases), missing data (2 cases) or change in anesthesiologic management (2 cases). The mean decrease in systolic pressure in the CI+ group was 53.8 ± 15.3 compared to 35.8 ± 18.1 mmHg in CI- patients (P = 0.0001). The relative mean arterial pressure change medians were 34.1% (IQR 23.2-43.0%) and 24.2% (IQR 17.2-30.2%), respectively (P = 0.0029). The ROC curve analysis for IVCCI showed an AUC of 64.8% (95% CI 52.1-77.5%). The selected 50% level of the IVCCI had a sensitivity of only 45.5% (95% CI 28.1-63.7%), but the specificity was high at 90.0% (78.2-96.7%). The positive predictive value was 75.0% (95% CI 50.9-91.3%), and the negative predictive value was 71.4% (95% CI 58.7-82.1%). CONCLUSION: In spontaneously breathing preoperative noncardiac surgical patients, preoperatively detected IVCCI≧50% can predict postinduction hypotension with high specificity but low sensitivity. Despite moderate performance, IVCCI is an easy, noninvasive and attractive option to identify patients at risk and should be explored further.

Importance of Fc Receptor γ-Chain ITAM Tyrosines in Neutrophil Activation and in vivo Autoimmune Arthritis.

Activating Fcγ receptors associated with Fc receptor γ-chain (FcRγ) are critical for mediating neutrophil effector functions in immune complex-mediated autoimmune diseases. FcRγ contains ITAM tyrosines and the in vivo role of these tyrosines has not been defined in neutrophils and arthritis. In this study, the in vivo functions of FcRγ ITAM tyrosines were characterized using wild type and ITAM tyrosine mutant (Y65F/Y76F) transgenic mice crossed to an FcRγ-deficient genetic background. FcRγ-deficient neutrophils showed undetectable cell surface expression of the activating Fcγ receptor IV, defective immune complex-induced superoxide production, degranulation and spreading. Although the re-expression of both the wild type and the ITAM tyrosine mutant (Y65F/Y76F) FcRγ could restore activating Fcγ receptor expression of FcRγ-deficient neutrophils, only the wild type transgenic form could mediate Fcγ receptor-dependent effector functions. In contrast, neutrophils carrying ITAM tyrosine mutant FcRγ were unable to produce superoxide, mediate degranulation and perform active spreading. In addition, our results confirmed the protection of FcRγ-deficient mice from autoimmune arthritis. Importantly, the presence of the wild type FcRγ transgene, in contrast to the ITAM tyrosine mutant transgene, partially reversed autoimmune arthritis development. The reversing effect of the wild type transgene was even more robust when animals carried the wild type transgene in a homozygous form. Collectively, FcRγ ITAM tyrosines play a critical role in the induction of neutrophil effector responses, the initiation and progression of an autoantibody-induced experimental arthritis in vivo, indicating a signaling, rather than just a receptor stabilizing function of the molecule.

[Identification of risk factors of multiresistant infections on two intensive care units]. / A multirezisztens infekciók rizikófaktorainak vizsgálata két intenzív osztályon.

INTRODUCTION: Intensive care units are favourable environment for infections, many of them are caused by antibiotic resistant bacteria. AIM: Identifying risk factors of ICU-acquired multiresistant infections. METHOD: We performed observational study on two academic intensive care units (a multidisciplinary and a surgical ICU) between 01/09/2014 and 30/11/2015. Patients with a first infection caused by predefined organisms (P. aeruginosa, E. coli, K. pneumoniae, A. baumanni, S. aureus, S. epidermidis, E. faecium, E. faecalis or their multiresistant homologues) verified ≥48 h following admission were divided into two groups according to multiresistant (MRB) and non-multiresistant (n-MRB) bacteria. Prevalence of diabetes, COPD, smoking, alcoholism, acute surgery, malignancy were recorded. Their role was evaluated on pooled populations. Illness severity was marked by SAPS-II at admission and SOFA-score on day of positive culture. We also noted the length of stay, mechanical ventilation, antibiotic treatment. RESULTS: Multidisciplinary ICU had 627, the surgical 1096 admissions. On the formal unit MRB group had 41 (48.1%), the n-MRB had 38 (51.9%) patients. On the latter unit 31 (54.4%) and 26 (45.6%) patients were involved. Smoking favoured multiresistant bacteria (RR 1.44 CI95% 1.04-2.0; p = 0.048). In case of malignancies n-MRB were more prominent (RR of MRB 0.68 CI95% 0.47-0.97; p = 0.026), other comorbidities had no significant impact. Illness severity scores did not differ at any of the ICUs. Preceding length of stay, days on mechanical ventilation or on antibiotics were similar in each group on both ICUs. CONCLUSION: Smoking was revealed as a risk factor for MRB on our ICUs. We were not able to identify time-dependent risk factors. Orv Hetil. 2017; 158(32): 1259-1268.

[Outbreak of vancomycin-resistant enterococci in a surgical intensive care unit]. / Vancomycinrezisztens Enterococcusok megjelenése sebészeti intenzív osztályon.

INTRODUCTION: Enterococci have increasing importance in intensive care units, and vancomycin-resistant strains express a new challenge. AIM: The aim of the authors was to present their findings obtained from the first vancomycin-resistant enterococci outbreak occurred in 2013 at the Intensive Care Unit of the 1st Department of Surgery, Semmelweis University. METHOD: This was a case-control study of patients who had Enterococci species isolated from their microbiological samples between January 1 and June 30, 2013. Changes of Enterococcal incidence and consequences of vancomycin-resistance in patient outcome were analyzed. Demographic data, hospital length of stay and mortality data were also collected. RESULTS: Enterococci were isolated from 114 patients and 14 of them had vancomycin-resistant strains. The incidence of Enterococcal strains was not different in the periods before and after the outbreak of the first vancomycin-resistant Enterococci. Patients with vancomycin-resistant Enterococci had significantly higher mortality rate than those with vancomycin-sensitive Enterococcus (42.9% vs 30.0%, p = 0.005); however, length of stay was not significantly different. Co-morbidities and emergency surgery were significantly higher in patients who had vancomycin-resistant Enterococci. CONCLUSIONS: The higher mortality observed in patients with vancomycin-resistant Enterococcus infections highlights the importance of prevention and appropriate infection control, however, the direct relationship of vancomycin-resistance and increased mortality is questionable.