Peripheral Line Research Articles

Geogenic particles induce bronchial susceptibility to non-typeable Haemophilus influenzae

Exposure to geogenic (earth-derived) particulate matter (PM) is linked to an increased prevalence of bronchiectasis and other respiratory infections in Australian Indigenous communities. Experimental studies have shown that the concentration of iron in geogenic PM is associated with the magnitude of respiratory health effects, however, the mechanism is unclear. We investigated the effect of geogenic PM and iron oxide on the invasiveness of non-typeable Haemophilus influenzae (NTHi). Peripheral blood mononuclear cell-derived macrophages or epithelial cell lines (A549 & BEAS-2B) were exposed to whole geogenic PM, their primary constituents (haematite, magnetite or silica) or diesel exhaust particles (DEP). The uptake of bacteria was quantified by flow cytometry and whole genome sequencing (WGS) was performed on NTHi strains. Geogenic PM increased the invasiveness of NTHi in bronchial epithelial cells. Of the primary constituents, haematite also increased NTHi invasion with magnetite and silica having significantly less impact. Furthermore, we observed varying levels of invasiveness amongst NTHi isolates. WGS analysis suggested isolates with more genes associated with heme acquisition were more virulent in BEAS-2B cells. The present study suggests that geogenic particles can increase the susceptibility of bronchial epithelial cells to select bacterial pathogens in vitro, a response primarily driven by haematite content in the dust. This demonstrates a potential mechanism linking exposure to iron-laden geogenic PM and high rates of chronic respiratory infections in remote communities in arid environments.

Blocking Th2 Signaling Pathway Alleviates the Clinical Symptoms and Inflammation in Allergic Conjunctivitis.

To explore the role of Th2 signaling pathway in allergic conjunctivitis (AC). Serum Th2 cytokines IL-4 or IL-13 of patients with AC were detected using the Meso scale discovery assay to verify the correlation of Th2 immunity and AC pathogenesis. Wistar Han rats were intraperitoneally and subcutaneously injected with ovalbumin (OVA) to establish an experimental AC model and the Th2 signaling pathway was blocked by an investigational neutralizing antibody (CM310). Serum IgE and OVA-specific IgE were detected by ELISA. Conjunctivitis inflammation, infiltration of eosinophils, and mast cell degranulation were detected by histological examination. Immortalized human conjunctival epithelial cells, a conjunctival epithelial cell line, and peripheral blood mononuclear cells of patients with AC were used as the target cells to study the impact of IL-4 or IL-13 on AC progression. Finally, a STAT6 reporter gene system was constructed using immortalized human conjunctival epithelial cells to confirm whether the downstream signaling pathway activated by IL-4 or IL-13. Serum IL-4 or IL-13 were increased in patients with AC versus healthy individuals. In an OVA-induced rat experimental AC model, blocking the Th2 signaling pathway with CM310, an investigational neutralizing antibody, alleviated the conjunctival symptoms, and decreased serum IgE, suppressed infiltration of eosinophils and mast cell degranulation. Further, an in vitro model showed CM310 suppressed the secretion of inflammatory cytokine from both immune cells and epithelial cells in both patients peripheral blood mononuclear cells and cell line. Blocking Th2 signaling pathway alleviates the clinical symptoms and inflammation in AC.

The influence of middle-aged male driver profile on driving performance and the effects of three perceptual countermeasures: A simulator study

The human-environment-vehicle triad and how it relates to crashes has long been a topic of discussion, in which the human factor is consistently seen as the leading cause. Recently, more sophisticated approaches to Road Safety have advocated for a road-driver interaction view, in which human characteristics influence road perception and road environment affects driver behavior. This study focuses on road-driver interaction by using a driving simulator. The objective is to investigate how the driver profile influences driving performance and the effects of three countermeasures (peripheral transverse lines before and after the beginning of the curves and roadside poles in the curves). Fifty-six middle-aged male participants drove a non-challenging rural highway simulated scenario based on a real road where many single-vehicle crashes occurred. The drivers' profiles were assessed through their behavioral history measured by a validated version of the Driver Behavior Questionnaire (DBQ) comprising three dimensions: Errors (E), Ordinary Violations (OV), and Aggressive Violations (AV). The relationship between speed and trajectory measures and drivers' profiles was investigated using random-parameter models with heterogeneity in the means. The models' results showed that the DBQ subscale scores in OV explained a considerable part of the heterogeneity found in drivers' performance. Furthermore, the heterogeneity in the means caused by the DBQ subscale scores in OV and E in the presence of peripheral transverse lines indicates a difference in how drivers react to the countermeasures. The peripheral lines were more efficient than roadside poles to moderate speed but did not positively influence all drivers' trajectories. Although the peripheral lines could be seen as an alternative to change driver behavior in a non-challenging or monotonous road environment, the design used in this study should be reviewed.

Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: the Fondazione Italiana Linfomi MCL0208 trial.

In the Fondazione Italiana Linfomi MCL0208 phase 3 trial, lenalidomide maintenance (LEN) after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL) improved progression-free survival (PFS) vs observation (OBS). The host pharmacogenetic background was analyzed to decipher whether single-nucleotide polymorphisms (SNPs) of genes encoding transmembrane transporters, metabolic enzymes, or cell-surface receptors might predict drug efficacy. Genotypes were obtained via real-time polymerase chain reaction of the peripheral blood germ line DNA. Polymorphisms of ABCB1 and VEGF were found in 69% and 79% of 278 patients, respectively, and predicted favorable PFS vs homozygous wild-type (WT) in the LEN arm was 3-year PFS of 85% vs 70% (P< .05) and 85% vs 60% (P< .01), respectively. Patients carrying both ABCB1 and VEGF WT had the poorest 3-year PFS (46%) and overall survival (76%); in fact, in these patients, LEN did not improve PFS vs OBS (3-year PFS, 44% vs 60%; P= .62). Moreover, the CRBN polymorphism (n= 28) was associated with lenalidomide dose reduction or discontinuation. Finally, ABCB1, NCF4, and GSTP1 polymorphisms predicted lower hematological toxicity during induction, whereas ABCB1 and CRBN polymorphisms predicted lower risk of grade ≥3 infections. This study demonstrates that specific SNPs represent candidate predictive biomarkers of immunochemotherapy toxicity and LEN efficacy after ASCT in MCL.

An engineered T-cell engager with selectivity for high mesothelin-expressing cells and activity in the presence of soluble mesothelin

ABSTRACT Mesothelin (MSLN) is an attractive immuno-oncology target, but the development of MSLN-targeting therapies has been impeded by tumor shedding of soluble MSLN (sMSLN), on-target off-tumor activity, and an immunosuppressive tumor microenvironment. We sought to engineer an antibody-based, MSLN-targeted T-cell engager (αMSLN/αCD3) with enhanced ability to discriminate high MSLN-expressing tumors from normal tissue, and activity in the presence of sMSLN. We also studied the in vivo antitumor efficacy of this molecule (NM28-2746) alone and in combination with the multifunctional checkpoint inhibitor/T-cell co-activator NM21-1480 (αPD-L1/α4-1BB). Cytotoxicity and T-cell activation induced by NM28-2746 were studied in co-cultures of peripheral blood mononuclear cells and cell lines exhibiting different levels of MSLN expression, including in the presence of soluble MSLN. Xenotransplant models of human pancreatic cancer were used to study the inhibition of tumor growth and stimulation of T-cell infiltration into tumors induced by NM28-2746 alone and in combination with NM21-1480. The bivalent αMSLN T-cell engager NM28-2746 potently induced T-cell activation and T-cell mediated cytotoxicity of high MSLN-expressing cells but had much lower potency against low MSLN-expressing cells. A monovalent counterpart of NM28-2746 had much lower ability to discriminate high MSLN-expressing from low MSLN-expressing cells. The bivalent molecule retained this discriminant ability in the presence of high concentrations of sMSLN. In xenograft models, NM28-2746 exhibited significant tumor suppressing activity, which was significantly enhanced by combination therapy with NM21-1480. NM28-2746, alone or in combination with NM21-1480, may overcome shortcomings of previous MSLN-targeted immuno-oncology drugs, exhibiting enhanced discrimination of high MSLN-expressing cell activity in the presence of sMSLN.

Evaluation of Upper Extremity Venous Thrombosis with Doppler Ultrasonography in Peripheral Venous Line Applied Patients

Objectives: Peripherally inserted venous lines (PVL) may increase the risk of venous thrombosis due to vessel wall disarrangement. Aim of this study is to identify the cases of upper extremity venous thrombosis (UEVT) related to PVL since most of the PVLs applied to upper extremities.&#x0D; Methods: Sixty-nine hospitalized patients with previous or present PVL insertions were included in this prospective study. Upper extremity Doppler compression ultrasonography (USG) examination were performed to on all patients. The cases with detected UEVTs were evaluated as group 1 and the remaining cases were evaluated as group 2. Demographic parameters, PVL applications, intravenous treatments were compared between the groups.&#x0D; Results: UEVT was diagnosed by Doppler USG in 26 (37.7%) patients out of 69 patients. Lower extremity thrombosis was found in 10 (14.49%) patients. UEVT was observed in cephalic vein in 14 (53.8%) and in basilic vein in four (15.4%) out of 26 (37.7%) patients. Axillary and brachial deep UEVT was located in two (2.9%) cases. Superficial UEVT was found in 24 (34.8%) cases. Ceftriaxone, cefoperazone/sulbactam and esomeprazole were the mostly associated treatments with UEVT. UEVT was detected in five patients with PVL that were inserted only for drawing blood.&#x0D; Conclusion: PVL is a risk factor for UEVT since almost 1/3 of the patients revealed UEVT. When PVL is no longer needed or the need for intravenous therapy decreases, oral therapy should be planned and PVL should be removed. Removal of PVL appears to be necessary to avoid UEVT.

Comparison of extravasation events related to the peripheral administration of vasopressors prior to and following implementation of an institutional protocol

AbstractIntroductionFollowing adequate fluid resuscitation, vasopressors are often utilized to maintain perfusion in shock states. Traditionally, vasopressors are administered via a central venous catheter (CVC) to attempt to minimize extravasation events. New literature advocates for peripheral vasopressor administration when CVC placement could lead to a delay in care. The purpose of this study was to compare extravasation events during vasopressor administration via a peripheral intravenous line (PIV) prior to and following the implementation of an institutional peripheral vasopressor protocol.MethodsThis was a single‐center, retrospective, observational study conducted at a large academic medical center. Adult patients admitted to an intensive care unit (ICU) from September 2018 to 2020 who received continuous infusion vasopressors were included. Vasopressors evaluated were norepinephrine, epinephrine, phenylephrine, dopamine, and vasopressin. The primary outcome evaluated extravasation events prior to and following the implementation of an institutional peripheral vasopressor protocol.ResultsOf the 3430 patients included, 1532 and 1898 patients were in the pre‐ and post‐protocol implementation groups. Following protocol implementation, there was an increase in PIV utilization, improvement in ultrasound‐guided PIV placement (17% vs. 26%, p &lt; 0.001), and line assessment every 2 h (74% vs. 90%, p &lt; 0.001). Less non‐compliance in vasopressor infusion rates (40% vs. 24%, p &lt; 0.001) and PIV location (18% vs. 10%, p &lt; 0.001) were also observed following protocol implementation. A total of 58 extravasation events occurred in both groups, 15 confirmed events and 43 suspected events. Following protocol implementation, there were less extravasation events (2.4% [n = 37] pre‐ vs. 1.1% [n = 21] post‐protocol p = 0.003).ConclusionFollowing the implementation of an institutional protocol, there was a reduction in extravasation events, an improvement in ultrasound‐guided PIV placement, and the use of peripheral infusion practices associated with increased safety. Additional studies are needed to determine the optimal peripheral vasopressor protocol to reduce CVC use and maintain reduced extravasation events.

Evaluating the Effect of Nursing-Performed Point-of-Care Ultrasound on Septic Emergency Department Patients.

Introduction Nursing-performed point-of-care ultrasound (NP-POCUS) studies have been performed on applications such as ultrasound-guided peripheral intravenous line placement and assessing bladder volume. However, research on the use of NP-POCUS in the management of septic patients remains limited. The purpose of this quality improvement study was to investigate how NP-POCUS could impact fluid treatment decisions affecting septic patients in the emergency department (ED)using a focused IVC and lung ultrasound protocol. Methods Nurses received standardized training in POCUS and performed inferior vena cava (IVC) and lung ultrasound scans on septic patients in the ED at predetermined intervals (hours: zero, three, and six). Based on their findings, they were asked to make recommendations on fluid management. Emergency physicians (EPs), both residents and attendings, are providing recommendations for fluid management without the use of ultrasound, which is being compared to the nurse-driven POCUS assessment of fluid management. EPs reviewed the NP-POCUS assessments of patient fluid status to determine nursing accuracy. Results A total of 104 patients were scanned, with a mean age of 60.7 years. EPs agreed with nursing ultrasound assessments in 99.1% of cases. Nursing ultrasound images changed management or increased physician confidence in current treatment plans83.7% and 96.6% of the time, respectively. Before reviewing saved nursing ultrasound images, EPs underestimated fluid tolerance in 37.5% of cases, overestimated fluid tolerance in 26% of cases, and correctly estimated fluid tolerance (within 500 ml) in 36.5% of cases. Throughout resuscitation, IVCs became less collapsible, the number of cases with B-lines was essentially unchanged, and less fluid was recommended. Conclusion This study demonstrated that nurse-performed POCUS is feasible and may have a meaningful impact on how physicians manage septic patients in the emergency department.

The Persistence of COVID-19-Related Pancytopenia as A Possible Sign of Hairy Cell Leukemia: A Case Report

COVID-19 is known to cause many hematological abnormalities, such as thrombocytopenia, leucopenia, and lymphopenia. Pancytopenia, a decrease in all peripheral blood cell lines, is a rare complication not commonly seen in patients with COVID-19. We report a case of a patient who experienced COVID-19 infection with mild clinical symptoms like fever, fatigue, and muscle and bone aches. The laboratory examinations revealed pancytopenia, mainly neutropenia, thrombocytopenia, mild anemia, and relative lymphocytosis, which persisted after infection resolution. The splenomegaly in abdominal echography and the characteristics of lymphocyte elements in peripheral blood smear examination raised suspicion of the presence of hairy cell leukemia (HCL); therefore, the patient was further examined with a bone marrow biopsy, which confirmed the diagnosis. The persistence of pancytopenia after recovery from COVID-19 infection, especially in patients with splenomegaly, should raise suspicion of another hematological coexistence diagnosis like HCL.

Use of Routine Emergency Department Care Practices with Deaf American Sign Language Users

BackgroundDeaf individuals who communicate using American Sign Language (ASL) seem to experience a range of disparities in health care, but there are few empirical data. ObjectiveTo examine the provision of common care practices in the emergency department (ED) to this population. MethodsED visits in 2018 at a U.S. academic medical center were assessed retrospectively in Deaf adults who primarily use ASL (n = 257) and hearing individuals who primarily use English, selected at random (n = 429). Logistic regression analyses adjusted for confounders compared the groups on the provision or nonprovision of four routine ED care practices (i.e., laboratories ordered, medications ordered, images ordered, placement of peripheral intravenous line [PIV]) and on ED disposition (admitted to hospital or not admitted). ResultsThe ED encounters with Deaf ASL users were less likely to include laboratory tests being ordered: adjusted odds ratio 0.68 and 95% confidence interval 0.47–0.97. ED encounters with Deaf individuals were also less likely to include PIV placement, less likely to result in images being ordered in the ED care of ASL users of high acuity compared with English users of high acuity (but not low acuity), and less likely to result in hospital admission. ConclusionResults suggest disparate provision of several types of routine ED care for adult Deaf ASL users. Limitations include the observational study design at a single site and reliance on the medical record, underscoring the need for further research and potential reasons for disparate ED care with Deaf individuals.

Lipid metabolism reprogramming roles in mantel cell lymphoma growth and survival

Introduction: Metabolic reprogramming is a hallmark of cancer progression. However, there are few studies in mantle cell lymphoma (MCL). Protein arginine methyltransferase 5 (PRMT5), catalyzes monomethylation and symmetric demethylation of arginine residues on histone and nonhistone proteins and participates in tumor progression. This study aimed to investigate the mechanism of PRMT5-induced lipid reprogramming in MCL. Method: Lymph node, bone marrow biopsy, peripheral blood specimens and MCL cell lines were utilized as models. Liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based analysis was performed to measure the steady-state level of metabolites. GSE93291 dataset and immunohistochemistry (IHC) staining were utilized to determine the relationship between expression levels of PRMT5 and patient outcome. CRISPR/Cas9 editing was employed to engineer the loss-of-function models of PRMT5 and other key genes involved in lipid metabolism. Result: Non-targeted LC-MS/MS analysis showed that lipid metabolites were rich in MCL cell lines (Figure 1A and 1B). Through systematic analysis of the relationship between lipid metabolism-related genes and MCL prognosis in GSE93291, PRMT5, SREBP1, SRENP2, FASN and MYC were found to be associated with the overall survival (OS) of MCL patients (Figure 1F–1J), which suggested that lipid metabolism reprogramming may be involved in the development of MCL. IHC staining of PRMT5 in 105 MCL tissues confirmed that elevated PRMT5 expression was significantly associated with poor progression free survival (PFS) (P = 0.039) and OS (P < 0.001) in MCL patients (Figure 1D and 1E). Multivariate Cox regression analysis showed that high PRMT5 expression was an independent prognostic indicator of OS (P = 0.003). Gene transcriptome sequencing showed downregulation of the PRMT5 caused the reduced expression of SREBP1/SREBP2 and FASN and change the expression of lipid metabolite (Figure 1K). PRMT5, SREBP1/SREBP2 and FASN depletion significantly impaired outgrowth and increased apoptosis of MCL cells. In primary tumor samples, MYC protein levels were significantly correlated with PRMT5 protein levels (P < 0.001). PRMT5 knockout blocked MYC mRNA and protein expression, suggesting a requisite role of PRMT5 in MYC transcription regulation. Further molecular biological methods were used to verify that PRMT5 could participate in lipid metabolism reprogramming through MYC by changing the expression levels of SREBP1/SREBP2 and FASN (Figure 1L). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers, Metabolism No conflicts of interests pertinent to the abstract.

CTPS1 acts as a prognostic biomarker and therapeutic target in mantle cell lymphoma

Introduction: Mantle cell lymphoma (MCL) represents 6 to 8% of non-Hodgkin’s lymphoma with generally poor prognosis. Cytidine triphosphate synthase 1 (CTPS1) is a critical regulatory enzyme in cytidine metabolism, catalyzing the rate-limiting step in de novo CTP synthesis. Herein, we aim to investigate the clinical significance and functional mechanisms of CTPS1 in MCL patients. Methods: Lymph node, bone marrow biopsy, peripheral blood specimens and MCL cell lines were utilized as models. Liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based analysis was performed to measure the steady-state level of metabolites. GSE93291 dataset and immunohistochemistry (IHC) staining were utilized to determine the relationship between expression levels of CTPS1 and patient outcome. CRISPR/Cas9 editing was employed to engineer the loss-of-function models of CTPS1 and other key enzymes involved in CTP synthesis. Results: Metabolic Profiling revealed dramatically aberrant cellular abundance of metabolic intermediates in the CTP synthesis pathway (Figure 1A). For GSE93291 analysis, a nucleotide metabolism related prognostic model was established by bioinformatic analysis and CTPS1 was screened out by highest regression coefficient (Figure 1B). IHC staining of CTPS1 in 105 MCL tissues confirmed that elevated CTPS1 expression was significantly associated with poor PFS (P = 0.038) and OS (P = 0.001) in MCL patients (Figure 1C-D). Multivariate Cox regression analysis showed that high CTPS1 expression was an independent prognostic indicator of both PFS and OS. CTPS1 depletion significantly impaired outgrowth and increased apoptosis of MCL cells, suggesting that CTPS1 is the major isozyme important for MCL survival (Figure 1E-F). In primary tumor samples, MYC protein levels were significantly correlated with CTPS1 protein levels (P < 0.001, R = 0.638). MYC knockout blocked CTPS1 mRNA and protein expression prior to induction of cell death, suggesting a requisite role of MYC in CTPS1 transcription regulation (Figure 1G). Remarkably, TP53 aberrant and ibrutinib-resistant MCL cells rely on cytidine metabolism (Figure 1H). Genetic or chemical inhibition (3-deazauridine) of CTPS1 reversed poor responsiveness of MCL cell lines to ibrutinib (Figure 1I). Cytidine level was significantly increased in TP53-deficient MCL cells and the effect of CTPS1 inhibition was independent of TP53 status (Figure 1K). Gene set enrichment analysis of RNA-sequencing revealed that CTPS1 inhibition induced DNA damage and apoptosis. Moreover, CTPS1 inhibition caused cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation, which triggered innate immune pathway, leading to cells growth inhibition (Figure 1L). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers, Metabolism No conflicts of interests pertinent to the abstract.

Management of adverse effects in hyperosmolar therapy of brain edema

Background: Mannitol and hypertonic saline are the most frequently used hyperosmolar agents to treat cerebral edema resulting from acute brain injury. However, there are several issues with using hyperosmolar therapies. Here, we focus on the potential adverse effects of hyperosmolar therapies and practical tips to overcome these issues in the neurointensive care unit.Current Concepts: Among the hyperosmolar agents used, mannitol may decrease intravascular volume and pose a potential risk of acute kidney injury for patients. Complications associated with using hypertonic saline include the risk of central pontine myelinolysis, coagulopathy, electrolyte imbalances, metabolic acidosis, and pulmonary edema. In addition, prolonged use of hypertonic saline increases the risk of hyperchloremic metabolic acidosis, which may be overcome with the concomitant use of sodium acetate.Discussion and Conclusion: Several laboratory variables were monitored in the neurointensive care unit to limit and possibly detect early complications related to hyperosmolar therapies. When using hyperosmolar agents, including mannitol and hypertonic saline, for therapeutic purposes in patients with cerebral edema, determining whether to use peripheral or central lines and determining the appropriate rate and infusion dose can minimize their adverse effects. Clinicians need to be aware of the potential adverse events of administering hyperosmolar agents.

Comparison Between Pulsed and Continuous Accelerated Corneal Cross-Linking Protocols.

To compare between two accelerated corneal cross-linking (A-CXL) protocols in the management of keratoconus (KC) as regard to the extent of corneal treatment. This retrospective, comparative study included patients having mild to moderate, progressive KC. The study population was divided into two groups; group 1 enrolled 103 eyes of 62 patients who received pulsed light A-CXL (pl-CXL) at a power of 30 mW/cm2 with an irradiation time of 4 minutes, while group 2 comprised 87 eyes of 51 patients who received continuous light A-CXL (cl-CXL) at a power of 12 mW/cm2 with an irradiation time of 10 minutes. Recordings of the central and peripheral demarcation line depths (DD), and the maximum (DDmax) and minimum (DDmin) DD, using anterior segment optical coherence tomography, were compared between the two studied groups one month after the treatment protocol. Treatment stability was also evaluated pre and postoperatively (one year following surgery) by comparing the refractive and keratometric outcomes in both groups. The differences between the preoperative corneal thickness (minimum and central) and the epithelial thickness measurements between both groups were not statistically significant. Although group 1 had slightly larger central DD (223.4 ± 62.3 um), DDmax (240.4 ± 61.8 um), and DDmin (201 ± 54 um) than those of group 2 (221.8 ± 37 um, 229.1 ± 38.4 um, and 212 ± 37.2 um, respectively), the differences between both groups' measurements were not statistically significant. Also, the two groups showed statistically insignificant differences regarding the subjective refraction and the average and maximum keratometry pre and postoperatively, denoting visual, refractive, and keratometric stability in both groups. Longer duration cl-CXL seems to be as effective as pl-CXL regarding both postoperative stability and the extent of corneal tissue penetration by the ultraviolet treatment.

Sources of primary bloodstream infections in internal medicine patients – a cohort study

PurposeTo describe the sources of bloodstream infections (BSIs) in internal-medicine patients, on admission and during hospitalization, and to determine the proportion of BSIs in which no secondary cause could be defined (i.e., primary-BSI). MethodsWe analyzed all BSIs at the internal-medicine wards of the two campuses of the Hadassah Hebrew-University Medical Center, during 2017–2018. We defined the BSI source of each event (secondary, Central-line associated BSI (CLABSI) or primary non-CLABSI) and compared BSIs present on admission (POA) to hospital acquired (HA). ResultsThere were 595 patient-unique BSI events, 316 (53.1%) POA-BSI and 279 (46.9%) HA-BSI. Overall, 309 (51.9%) were secondary, 194 (32.6%) primary non-CLABSI and 92 (15.5%) CLABSI. Primary non-CLABSI in the POA-BSI group was 20.6% vs. 46.2% in the HA-BSI group (p = 0.001). The length of hospital stay (LOS) of the HA-BSI group was longer than in the POA-BSI group (mean LOS, 19 days vs. 13.6 days, p = 0.01) and mortality rate was higher (48.7% vs. 19%, p = 0.001). Staphylococcus aureus was more common in primary non-CLABSI than in CLABSI and secondary BSI (29.5%, 12.8% and 16.2%, respectively). ConclusionsThe proportion of primary non-CLABSI among HA-BSI events is very high (46.2%). The absence of any plausible source for these BSIs, and the fact that in our hospital more than 90% of patients in medicine wards have peripheral lines, suggests that these may be a possible source for primary non-CLABSIs. Measures to prevent peripheral-line associated BSI (PLABSI), like those implemented successfully for the prevention of CLABSI, should be considered.

Evaluation of hospital-onset bloodstream infections compared to central line...associated bloodstream infections at an acute, tertiary care hospital

CLABSI is the current benchmark used in HAI surveillance and effective interventions have greatly reduced the incidence in recent years. However, BSIs continue to be a major source of morbidity and mortality in hospitals. HOBSI, which includes central and peripheral line surveillance, may be a more sensitive indicator of preventable BSI. Our objective is to assess the impact of a change to HOBSI surveillance by comparing the incidence of BSIs using the NHSN LabID and BSI definitions compared to CLABSI. Utilizing electronic medical charts, we determined if each blood culture met the HOBSI criteria according to the NHSN LabID and BSI definitions. We calculated the incidence rates per 10,000 patient-days for both definitions and compared them to the CLABSI rate per 10,000 patient-days for the same period. The incidence rate (IR) of HOBSI using the LabID definition was 10.25. Using the BSI definition, we found an IR of 3.77. The IR of CLABSI for the same period was 1.84. After excluding secondary BSIs, the HOBSI rate is still double that of the CLABSI rate. HOBSI surveillance is a more sensitive indicator of BSI than CLABSI, and thus a better target for monitoring effectiveness of interventions.

Comparative evaluation between external jugular and internal jugular venous catheterization through landmark technique.

Cannulation of a central vein is crucial in patients for hemodynamic management and when insertion of a peripheral line is not possible. The internal jugular vein is the preferred access site; however, in the case of not being accessible, the second cannulation site of choice is still unclear. The study aimed to access the feasibility of external jugular vein cannulation versus internal jugular vein cannulation in terms of success, cannulation time, number of attempts and complications. In this prospective, randomised double-blinded study, 100 patients received 7Fr size triple-lumen central vein catheter either in the internal jugular vein (n = 50) or external jugular vein (n = 50) through the landmark technique as a part of anaesthetic care in the operation theatre. The number of attempts, cannulation time and incidence of complications in both the techniques were observed and recorded. The success rate in internal jugular vein cannulation was 88%, while in the external jugular vein, it was 78% (p = 0.17). The external jugular vein cannulation was comparatively quicker in our study (p = 0.01). Similarly, elevated body mass index did not affect the success rate in the number of cannulations attempts in either group (p = 0.08). In terms of complications, the internal jugular vein group had a total of 20% and the external jugular vein group had 28% complications; however, the complications were more severe in the internal jugular vein group. Anaesthetists should rethink alternate routes for the insertion of central vein cannulation. The external jugular cannulation route is one of them.

Donkey whey proteins ameliorate dextran sulfate sodium-induced ulcerative colitis in mice by downregulating the S100A8-TRAF6-NF-κB axis-mediated inflammatory response

Donkey milk has a variety of physiological functions, including antibacterial and anti-inflammatory. Donkey whey proteins (DWPs), as the main functional component in donkey milk, its inhibitory effect on colitis is still unclear. In this study, the inhibitory effect and potential mechanism of DWPs on dextran sulfate sodium (DSS)-induced colitis were investigated. Firstly, the DWPs and bovine milk whey proteins (BWPs) were characterized using proteomics. Then, we administered DWPs and BWPs to mice with colitis via oral gavage. The results of immunohistochemistry and flow cytometry indicated that DWPs increased T regulatory cell accumulation and increased the abundance of the cluster of differentiation 205+ (CD205+) macrophages compared to those with BWPs and in model groups. In addition, DWPs exhibited a more remarkable ability to inhibit pro-inflammatory proteins (S100A8, TRAF6, and NF-κB) expression and inflammatory secretion than BWPs. In addition, DWPs significantly decreased NF-κB and CD86 levels more than BWPs or the negative control in both LPS-stimulated human peripheral blood mononuclear cells or cell lines. These findings indicate that DWPs comprise a promising anti-colitis functional food, and this work has established a foundation for future research on these compounds.

The Association Between Central Line-Associated Bloodstream Infection and Central Line Access.

Identifying modifiable risk factors associated with central line-associated bloodstream infections (CLABSIs) may lead to modifications to central line (CL) management. We hypothesize that the number of CL accesses per day is associated with an increased risk for CLABSI and that a significant fraction of CL access may be substituted with non-CL routes. We conducted a retrospective cohort study of patients with at least one CL device day from January 1, 2015, to December 31, 2019. A multivariate mixed-effects logistic regression model was used to estimate the association between the number of CL accesses in a given CL device day and prevalence of CLABSI within the following 3 days. A 395-bed pediatric academic medical center. Patients with at least one CL device day from January 1, 2015, to December 31, 2019. None. There were 138,411 eligible CL device days across 6,543 patients, with 639 device days within 3 days of a CLABSI (a total of 217 CLABSIs). The number of per-day CL accesses was independently associated with risk of CLABSI in the next 3 days (adjusted odds ratio, 1.007; 95% CI, 1.003-1.012; p = 0.002). Of medications administered through CLs, 88% were candidates for delivery through a peripheral line. On average, these accesses contributed a 6.3% increase in daily risk for CLABSI. The number of daily CL accesses is independently associated with risk of CLABSI in the next 3 days. In the pediatric population examined, most medications delivered through CLs could be safely administered peripherally. Efforts to reduce CL access may be an important strategy to include in contemporary CLABSI-prevention bundles.

A187 DIETARY FIBERS ELICIT GUT IMMUNE AND EPITHELIAL BARRIER MODIFYING EFFECTS IN INFLAMMATORY BOWEL DISEASES BASED ON FOOD SOURCE AND FIBER CHEMICAL FEATURES

Abstract Background Dietary fibers are not digested in the bowel; they are fermented by microbes, typically promoting gut health. However, IBD patients experience sensitivity to consumption of fibers. Our previous findings offered the first mechanistic evidence demonstrating that unfermented dietary β-fructans (inulin and oligofructose) can induce pro-inflammatory cytokines and altered epithelial barrier integrity in a subset of pediatric IBD colonic biopsies cultured ex vivo, and in the SYNERGY-1 (β-fructan) clinical study of adult remission UC patients. Fermentation of β-fructan by whole-microbiota intestinal washes from non-IBD or remission IBD patients (but not non-IBD microbes) reduced pro-inflammatory responses. Purpose Here we aimed to expand our findings to uncover the physiologically relevant gut immune and epithelial responses to over 50 unfermented and partially fermented dietary fibers (arabinoxylans, β-glucans, β-mannans, galatooligosaccharides, inulins, oligofructoses, pectins, raffinooligosaccharides, xyloglucans) sourced from commonly consumed fruits, grains, and vegetables to better understand which foods are safe for IBD patients, and in which disease state settings. Method Colonic biopsies cultured ex vivo, peripheral blood mononuclear cells (PBMCs), colonic organoids, and cell lines were incubated with individual dietary fibers or mixture of fibers extracted from commonly consumed fruits, grains, and vegetables. Epithelial barrier integrity (TEER, microscopy, FITC-dextran) and immune responses (cytokine secretion [ELISA/MSD] and expression [qPCR]) were assessed. Structural features of the different fibers (e.g., degree of polymerization, phenolic/phytic content, branching, sugar content) were measured by HPLC and gas chromatography and correlated to host cell responses. Result(s) Most significantly unfermented inulin, oligofructose, and arabinoxylan induced pro-inflammatory responses, particularly in myeloid cells. Pectin and galatooligosaccharides were either non-inflammatory or anti-inflammatory depending on the food source. The epithelial barrier response to select dietary fibers correlated more significantly with the chemical properties of the fibers; longer fibers (greater degree of polymerization; e.g., inulin) displayed improved barrier integrity while shorter dietary fibers with higher phenolic content displayed reduced barrier integrity. Fiber structural properties varied significantly between different fiber subtypes along with the same fiber subtype sourced from different foods. Conclusion(s) Our findings suggest that intolerance and avoidance of fibers in select IBD patients occurs in patients whose gut microbiota do not support fermentation of fibers resulting in increased presence of unfermented dietary fibers in the gut. Here we show which specific dietary fibers from specific food items can elicit gut barrier damage and inflammation in the gut dependent on fiber structural features, suggesting mechanisms underlying IBD patient avoidance of specific high-fiber foods. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Weston Family Foundation, MMSF, NSERC, CRC Disclosure of Interest None Declared