Umbilical Line Research Articles

Perfluorooctane sulfonate causes DNA damage and apoptosis via oxidative stress in umbilical cord fibroblast cells of Yangtze finless porpoise.

Yangtze finless porpoise (YFP) is a critically endangered species in China. It has been found that YFP is constantly exposed to perfluorooctane sulfonate (PFOS) in aquatic environments, leading to significant bioaccumulation. However, the impacts of PFOS on YFP health and survival are still unknown. To circumvent the limitations in YFP research, this study used YFP umbilical cord fibroblast cell line and exposed the cells to PFOS for 48h, with objectives to uncover the cytotoxicity and mechanisms of PFOS in YFP. A high-throughput proteomics assay showed that PFOS exposure at 50μM for 48h perturbed the proteome structure in YFP umbilical cord fibroblast cells. Functional annotation found the high relevance of oxidative stress, mitochondrial oxidative phosphorylation, and DNA damage to PFOS cytotoxic mechanisms. Concordantly, PFOS exposure significantly increased the deposition of reactive oxygen species (ROS) in YFP cells. The potential of mitochondria to produce ATP was also compromised by PFOS, which was accompanied by the higher permeability of mitochondrial membrane. In addition, exposure of YFP umbilical cord fibroblast cells to 50μM PFOS damaged the DNA assembly as evidenced by the increase in the percentage of DNA fragmentation. Gene transcription and enzymatic activity of caspases were up-regulated by PFOS, subsequently favoring the occurrence of early and late apoptosis. It was notable that ROS scavenger could successfully mitigate the cytotoxicity of PFOS on oxidative stress and apoptosis, thus pinpointing ROS as the molecular initiating event in apoptosis endpoints. To our knowledge, this is the first study that investigates the detrimental effects of PFOS using YFP umbilical cord fibroblast cells. The data will support an accurate assessment of ecological risks imposed by environmental pollutants on the health and sustainability of YFP, which is especially important under the context of sharp decline in YFP population and national initiative in YFP conservation.

How to Use POCUS to Place Umbilical Lines

How to Use POCUS to Place Umbilical Lines

Time to lymphoma treatment within 24 months in 'watch and wait' follicular lymphoma is associated with inferior outcomes: A multicentre analysis.

Some 'watch and wait' (W&W) FL patients suffer from rapid progression in a short term. Herein, we sought to identify these patients and also develop a risk score to screen them at diagnosis. Between 2008 and 2022, a total of 411 FL patients managed by the W&W strategy from 16 cancer centres were retrospectively enrolled in this study, and their time to lymphoma treatment (TLT) and progression-free survival (PFS) were evaluated. Thirty-five percent of W&W FL patients experienced TLT within 24 months (TLT24) after diagnosis. Their 5-year PFS rate was significantly lower than those without treatment at 24 months (62.3% vs. 89.5%). In multivariable analysis, five factors were identified as independent predictors of TLT24: stages III-IV, β2 microglobulin ≥3 mg/L, lymphocyte-to-monocyte ratio <3.8, bone marrow involvement and spleen enlargement (above umbilical line). Their AUCs for TLT24 were 0.76 (95% CI, 0.70-0.82) in the training cohort and 0.76 (95% CI, 0.67-0.85) in the validation cohort respectively. Risk groups were also associated with PFS (p < 0.001). In FL patients initially managed by W&W, TLT24 was associated with poor outcomes. This multivariable model helps screening for predicting TLT24, which may be useful to identify candidates for early interventional treatment.

Umbilical Line Securement Bundle to Reduce Line Loss in the Neonate.

Umbilical line migration not only increases the risks of complications but also results in malposition and, ultimately, loss of the umbilical line. To evaluate the use of an umbilical line securement bundle to reduce unintended line discontinuation after line adjustment in the neonate at a single 40-bed Level IV neonatal intensive care unit. A pre-post design of 75 neonates, preimplementation (n=50) and postimplementation (n=25), was analyzed using data collection from the electronic health record. There was a 37.5% absolute reduction in removal of the umbilical line due to malposition after line adjustment utilizing the umbilical line bundle, standardizing the adjustment order, nursing process, and follow-up x-ray evaluation. This absolute reduction has clinical significance although not statistically significant. Provider compliance rates with line adjustment order bundle were 75%, decreasing with additional adjustments (50%). Nursing staff reported comfort with umbilical line management, ranging from 63% to 87% on different tasks. The use of umbilical line bundles reduces rates of line discontinuation due to malposition. The adoption of umbilical line bundles in neonatal intensive care unit practice may help to prevent unintended line discontinuation. There is a need for continued research regarding the use of secondary securement devices for decreased rate of malposition and the timing and methods for surveillance of umbilical line position.

Cytotoxicity and mechanisms of perfluorobutane sulfonate (PFBS) in umbilical cord fibroblast cells of Yangtze finless porpoise

Yangtze finless porpoises (YFP) accumulate high levels of per- and polyfluoroalkyl substances (PFASs). However, the health impacts of PFASs to YFP are still unknown because it is technically and ethically unfeasible to use the critically endangered YFP in toxicological exposures. To uncover the potential toxicities of PFASs to YFP, this study exposed a YFP umbilical cord fibroblast cell line to perfluorobutane sulfonate (PFBS), an emerging PFASs pollutant in the aquatic environments. After exposure, the cytotoxicity and mechanisms of PFBS were explored. Our preliminary experiments found that PFBS compromised the cell viability in a concentration and duration dependent manner. In an exposure of 48-h duration, the maximum no observed effect concentration (NOEC) of PFBS was determined to be 400 µM. High-throughput proteomics were then conducted to identify the differentially expressed proteins in YFP cells exposed to 400 µM PFBS for 48 h. The results found that PFBS exposure significantly perturbed the proteome fingerprints of YFP umbilical cord fibroblast cells. Functional annotation of differential proteins showed that PFBS had the potential to impair a variety of biological processes associated with the immunity, oxidative stress, metabolism, and proteolysis. Consistently, the intracellular levels of reactive oxygen species (ROS) and proinflammatory cytokine IL-1β were significantly increased by PFBS in YFP umbilical cord fibroblast cells. Overall, this study highlights the toxic effects of emerging PFASs on YFP and provides reference data to evaluate the health risks of aquatic pollution under the context of national YFP protection. To our knowledge, this is the first omics study using YFP umbilical cord fibroblast cells in ecotoxicology of PFASs, which is applicable to various cetacean species and pollutants.

Abstract P211: Angiotensin-(2-7): A novel antihypertensive peptide of the renin-angiotensin-system

Recently, it has been described that acetyl-angiotensin (2-7)-amide (Ac-Ang-(2-7)-NH2) is a potent ACE inhibitor. In addition, the putative endogenous peptide angiotensin-(2-7) was also reported to be an ACE inhibitor. Here we tested the effect of Ang-(2-7) in blood pressure (BP) and isolated aortic rings of Wistar and SHR. In addition, we evaluated whether this hexapeptide stimulates receptors from the alternative renin-angiotensin system (RAS), including Mas, MrgD, and AT2R using CHO-transfected cells. To record BP and administer drugs, the femoral arterial and vein were cannulated. In the baseline period, BP was recorded for 1 hour. In bolus intravenous injection of Ang-(2-7) was performed at doses of 30, 6, and 2.4 μg/kg, in a volume of 0,1 ml/100g. After the injection BP and heart rate (HR) were recorded for six hours. Additionally, we evaluated the effect of Ang-(2-7) in isolated aortic rings from SHR and Wistar rats, pre-constricted with phenylephrine (10 -7 mol.L -1 ). The peptide effect was tested in the range of 10 -12 to 10 -6 molar. The effect of the peptide was also evaluated in endothelium-denuded rings. Furthermore, the effect of Ang-(2-7) was tested in rings pre-treated with the Mas/MrgD antagonist D-Pro 7 -Ang-(1-7) (10-6 μmol.L -1 ). Finally, we used NO intracellular measurements to test for the Ang-(2-7) activation of Mas, MrgD, or AT2 receptors using transfected-CHO cells. To confirm the effectiveness of Ang-(2-7) for NO production we used 4,5-diaminofluorescein-diacetate (DAF-FM diacetate) and the human umbilical vein cell line EA.hy926. Our data showed a progressive and marked reduction in BP reaching -40 mmHg (123±12mmHg;n=3) with 6 hours after 30ug/kg administration of injection of Ang-(2-7). There was no significant effect on Blood pressure in Wistar rats after injection. The aortic rings had a vasorelaxing effect of the Ang-(2-7) in both Wistar and SHR, which was abolished after endothelium was removed. The vasorelaxant effect of Ang-(2-7) was abolished by pre-treatment with D-Pro 7 -Ang-(1-7). Accordingly, Ang-(2-7) induced NO production in EA.hy926 and MrgD-transfected CHO cells. A slight effect on NO production was also observed in AT2-transfected cells. In conclusion, we have identified a new biologically active component of the RAS with a potent antihypertensive effect in SHR. Our results suggest an important contribution of MrgD/NO to the Ang-(2-7) cardiovascular effects.

Neonatal Resuscitation and Delivery Room Care: A Changing Global Landscape.

With 98% of neonatal deaths occurring in low- and middle-income countries (LMICs), leading health organizations continue to focus on global reduction of neonatal mortality. The presence of a skilled clinician at delivery has been shown to decrease mortality. However, there remain significant barriers to training and maintaining clinician skills and ensuring that facility-specific resources are consistently available to deliver the most essential, evidence-based newborn care. The dynamic nature of resource availability poses an additional challenge for essential newborn care educators in LMICs. With increasing access to advanced neonatal resuscitation interventions (ie, airway devices, code medications, umbilical line placement), the international health-care community is tasked to consider how to best implement these practices safely and effectively in lower-resourced settings. Current educational training programs do not provide specific instructions on how to scale these advanced neonatal resuscitation training components to match available materials, staff proficiency, and system infrastructure. Individual facilities are often faced with adapting content for their local context and capabilities. In this review, we discuss considerations surrounding curriculum adaptation to meet the needs of a rapidly changing landscape of resource availability in LMICs to ensure safety, equity, scalability, and sustainability.

OGG1 prevents atherosclerosis-induced vascular endothelial cell injury through mediating DNA damage repair.

This study was designed to investigate the role of 8-oxoguanine DNA glycosylase 1 (OGG1) in preventing atherosclerosis-induced vascular EC injury, thereby providing a theoretical basis for the exploration of drug targets and treatment methods for atherosclerosis. Human umbilical vein cell line (EA.hy926) was treated with ox-LDL to construct an in vitro atherosclerotic cell model. pcDNA3.1-OGG1 was transfected into EA.hy926 cells to overexpress OGG1. qRT-PCR, CCK-8 assay, flow cytometry, oil red O staining, ELISA, comet assay and western blot were used to evaluate the OGG1 expression, viability, apoptosis level, lipid droplet content, 8-OHdG level and DNA damage of cells in each group. Compared with the Control group, ox-LDL stimulation of endothelial cells significantly decreased cell viability, promoted apoptosis and DNA damage, and increased intracellular levels of 8-OHdG and γH2AX, while decreasing protein levels of PPARγ, FASN, FABP4, RAD51 and POLB. However, overexpression of OGG1 can significantly inhibit ox-LDL damage to endothelial cells, promote lipid metabolism, decrease lipid droplet content, and improve DNA repair function. Over-expression of OGG1 improves DNA repair. Briefly, OGG1 over-expression enhances the DNA damage repair of ECs by regulating the expression levels of γH2AX, RAD51 and POLB, thereby enhancing cell viability and reducing apoptosis.

A New Formula for Estimating Insertion Length of Umbilical Catheters in Neonates: An Observational Study

Objective: Current formulae used by clinicians to estimate the insertion length of umbilical catheters are inaccurate. We aimed to derive a new model that could improve accuracy in estimating the insertion length of umbilical catheters. Study design: This was a multi-centre prospective observational study of neonates admitted to neonatal units and needing umbilical line(s) inserted for clinical reasons. Demographic data, catheter-related measurements and a new external length measurement—sternal notch to the umbilicus, were collected at three tertiary-level neonatal units in South Wales, UK. Generalised linear models were used to estimate the fit of the external length, birthweight, gestation and head circumference with catheter length and to derive a formula. The best fit was estimated by comparing r 2 values for each equation. Results: Data from 113 infants for each venous and arterial line were analysed for the new mathematical formulae. For both umbilical arterial catheterisation [[Formula: see text] and umbilical venous catheter (UVC) [[Formula: see text]], a quadratic model based on birthweight was found to have the best fit for predicting the insertion length of the catheters. However, the overall fit for UVCs was poorer for all explanatory variables ( y = estimated insertion length of the umbilical catheter in cm, x = birthweight in kg). Conclusion: Our prospective multi-centre observational study identified a quadratic model based on birthweight as the best fit for estimating the insertion length of umbilical lines in neonates. This is a new finding and further development on earlier birthweight-based linear models.

Central-line-associated bloodstream infection burden among Dutch neonatal intensive care units

The establishment of an epidemiological overview provides valuable insights needed for the (future) dissemination of infection-prevention initiatives. To describe the nationwide epidemiology of central-line-associated bloodstream infections (CLABSI) among Dutch Neonatal Intensive Care Units (NICUs). Data from 2935 neonates born at <32 weeks' gestation and/or with a birth weight <1500g admitted to all nine Dutch NICUs over a two-year surveillance period (2019-2020) were analysed. Variations in baseline characteristics, CLABSI incidence per 1000 central-line days, pathogen distribution and CLABSI care bundles were evaluated. Multi-variable logistic mixed-modelling was used to identify significant predictors for CLABSI. A total of 1699 (58%) neonates received a central line, in which 160 CLABSI episodes were recorded. Coagulase-negative staphylococci were the most common infecting organisms of all CLABSI episodes (N=100, 63%). An almost six-fold difference in the CLABSI incidence between participating units was found (2.91-16.14 per 1000 line-days). Logistic mixed-modelling revealed longer central line dwell-time (adjusted odds ratio (aOR):1.08, P<0.001), umbilical lines (aOR:1.85, P=0.03) and single rooms (aOR:3.63, P=0.02) to be significant predictors of CLABSI. Variations in bundle elements included intravenous tubing care and antibiotic prophylaxis. CLABSI remains a common problem in preterm infants in The Netherlands, with substantial variation in incidence between centres. Being the largest collection of data on the burden of neonatal CLABSI in The Netherlands, this epidemiological overview provides a solid foundation for the development of a collaborative platform for continuous surveillance, ideally leading to refinement of national evidence-based guidelines. Future efforts should focus on ensuring availability and extraction of routine patient data in aggregated formats.

Human Umbilical Cord Perivascular Cells Prevent Tumor Growth in a Melanoma Tumor-Bearing Mouse Model and Modulate Breast Cancer and Melanoma Cells in a Cell Line-Dependent Manner In Vitro

First trimester (FTM) and term human umbilical cord perivascular cells are promising mesenchymal stromal cell candidates to mitigate side effects of oncotherapy, but their safety for cancer patients remains to be determined. This study was designed to determine if human umbilical cord perivascular cells modulate tumor growth when injected systemically in a tumor-bearing mouse model. Immunodeficient mice-bearing palpable subcutaneous SK-MEL-28 human melanoma tumors were randomized to receive a tail vein injection of three human umbilical cord perivascular cell lines resuspended in hank’s buffer saline solution (vehicle) or vehicle only, as a control. Fibroblast cells were included as a cell control in some experiments. Tumor size was monitored weekly and weighed at 3-weeks postinjection. Cell fate and tumor cell proliferation, apoptosis, vascularization as well as tumor-associated immune cells were assessed using immunostaining and flow cytometry. Serum tumor necrosis factor alpha and C-reactive protein levels were measured using enzyme-linked immunosorbent assays. Transwell coculture models were used to study the paracrine effects of multiple lines of human umbilical cord cells on human melanoma cell lines as well as breast cancer cell lines. Systemic administration of FTM and term human umbilical cord perivascular cells, but not fibroblast cells, prevented melanoma tumor growth in a tumor-bearing animal model by modulating tumor cell proliferation and systemic inflammatory mechanisms. Cancer cell- and donor-dependent paracrine effects on cancer cell growth were observed in vitro. Our preclinical studies thus suggest that, with regards to its effects on tumor growth, systemic administration of FTM and term human umbilical cord perivascular cells may be a safe cell therapy to address the side effects of cancer.

Novel Umbilical Catheter Securement and Protection Device for Umbilical Line Securement during Laparotomy.

Umbilical catheter malposition rate is high. We compared a Novel Umbilical Securement Device (NUSD) to standard methodologies for neonatal invasive care unit patients undergoing laparotomy. Retrospective study was performed on infants undergoing laparotomy from April 2019 to January 2023. Two neonatologists compared position of umbilical arterial catheter/umbilical venous catheter (UVC) on perioperative chest X-ray (CXRs) in patients with or without NUSD. Eighteen patients underwent laparotomy, of which 8 patients had NUSD (9 lines) and 10 patients did not (14 lines). In NUSD group, mean gestational age was 37 ± 4 weeks and mean birth weight was 2.3 ± 0.9 kg compared with 31 ± 8 weeks and 2.1 ± 1.4 kg in non-NUSD group, respectively. The mean age at surgery was 5 ± 7 and 5 ± 3 days, respectively. No malposition was seen in NUSD group, while 57% of UVCs (28% of lines) were malpositioned postoperatively in non-NUSD group (p = 0.048). NUSD is an umbilical catheter securement device with low malposition rate, specifically during perioperative period with heightened risk for dislodgement. · Umbilical catheters provide reliable access for neonates but have a high rate of malpositioning.. · NUSD is an umbilical catheter securement device with low malposition rate.. · NUSD can be kept in place during laparotomy and can decrease the risk of malpositioning..

Clinical utility of repeat fetal echocardiography in congenital heart disease.

To investigate the utility of repeat fetal echocardiography (FE) following a diagnosis of structural congenital heart disease (CHD) on the initial FE. We evaluated how often changes in management and counseling occurred based on subsequent FE findings and sought to determine which types of CHD were more likely to have changes in management and/or counseling based on repeat FE. This was a retrospective review of all patients who presented to our center between January 2012 and January 2019 and who had more than one FE performed for structural CHD. We reviewed consultation notes to determine whether management or counseling had changed based on FE findings at follow-up visits. Management variables included a change in location or mode of delivery, plan for atrial septostomy, initiation of prostaglandin infusion, umbilical line placement and planned admission location (nursery vs neonatal intensive care unit). We defined a counseling change as any of the above changes in management as well as any meaningful refinements in the cardiac diagnosis that led to a change in the overall prognosis or future management. Initial diagnoses were grouped into anatomically/hemodynamically relevant subgroups. Fisher's exact test was used to assess the relationship between the initial diagnosis and changes in management. Post-hoc pairwise comparisons were performed using Dunnett's test. Between January 2012 and January 2019, 267 patients underwent 534 follow-up FE assessments performed for structural CHD. Management change based on repeat FE occurred in 41/267 (15.4%) cases. A change in management was associated with the diagnosis made at the initial visit (P < 0.001). The proportion of cases with a management change was highest among those with an initial diagnosis of pulmonary valve abnormality/non-critical pulmonary stenosis (4/11 (36.4%)), followed by balanced atrioventricular canal (AVC) defect (5/17 (29.4%)) and left ventricular outflow tract obstruction/aortic valve abnormality or coarctation/interrupted aortic arch (19/68 (27.9%)). No management change occurred in fetuses diagnosed with isolated ventricular septal defect (VSD), truncus arteriosus, pulmonary vein anomaly or isolated arch sidedness/branching abnormality. Compared to those with a VSD, management was significantly more likely to be changed in fetuses with a balanced AVC defect (P = 0.025) and left heart lesions (P = 0.002). Right heart lesions showed a trend towards an increased incidence of management change (P = 0.05). A counseling change based on repeat FE occurred in 108/267 (40.4%) cases. The proportion of cases with a counseling change was highest among those with an initial diagnosis of pulmonary valve abnormality/non-critical pulmonary stenosis (8/11 (72.7%)) and hypoplastic left heart syndrome/critical aortic stenosis (5/9 (55.6%)). The clinical utility of follow-up FE is associated with the type of CHD diagnosed. Follow-up FE led to changes in management in several types of CHD, most commonly in cases with an initial diagnosis of right and left outflow obstructive lesions and balanced AVC defect. When developing programmatic protocols for the frequency of FE assessments, the type of CHD should be a major determinant, but additional studies are required to reach a consensus on how often serial FE should be performed for each type of CHD. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Sustaining extended Kangaroo mother care in stable low birthweight babies in NICU: a quality improvement collaborative of six centres of Karnataka

BackgroundKangaroo mother care (KMC) is a proven intervention for intact survival in preterms. Despite evidence, its adoption has been low. We used a point of care quality improvement (QI) approach...

Abdominal and cranial ultrasound screenings in our Neonatal Intensive Care Unit

Previously, all admitted neonates to our tertiary Neonatal Unit, University of Szeged, had a cranial and abdominal ultrasound performed as part of their care. To analyze the findings and to evaluate the effectiveness of the universal ultrasound screening. Results of cranial and abdominal ultrasound imaging performed in our Unit between 1st January 2014 and 31st December 2015 were analyzed retrospectively. Abnormalities found during the screening scans were studied further and assessed until discharge and during the first 2 years. All imagings were performed by a radiologist. During the examined 2 years, 579 neonates were admitted (gestational age mean 34.2 weeks [23-41, SD ± 4.04]), abdominal ultrasound was performed in 562 (97%) and cranial ultrasound in 560 (97%) babies, on the 3.6th day of life at an average (0-18, SD ± 2.24). Of all abdominal ultrasound scans, 87% (n = 488) was carried out as screening, and the found abnormalities in 140 (29%) of the cases: renal pelvic dilatation (n = 67 [47.9%]), free abdominal fluid (n = 17 [12.1%]), echogenic kidneys (n = 13 [9.3%]), congenital abnormalities of the kidney and urinary tract (n = 9 [6.4%]), abnormalities of the liver, bile system, adrenal gland [n = 14 [10%]). The screening identified 4 (0.8%) neonates with renal abnormilaties requiring surgical correction. In regards of renal abnormalities, we observed male (p = 0.18) and left sided (p = 0.54) predominance. Screening cranial ultrasound was performed in 65% (n = 362) of all neonates, discovering 51 (14%) anomalies: plexus chorioideus cyst (n = 21 [41%]), plexus chorioideus hemorrhage (n = 9 [17.6%]), mild ventricular asymmetry (n = 8 [15.7%]), subependymal hemorrhage (n = 5 [9.8%]), abnormalities of the periventricular area (n = 4 [7.8%]), colpocephaly, hydrocephalus externus, echogenic meninx and thalamic nodule [n = 1-1 (1.9-1.9%)]. Abdominal ultrasound screening discovered renal abnormalities and umbilical line complications as clinically relevant findings. However, a small number of renal abnormalities identified by screening required surgical intervention. Further studies are needed to identify possible risk groups to develop more efficient screening strategy to decrease the number of screened babies for 1 relevant finding (number to screen). Cranial ultrasound screening did not identify any abnormalities that needed intervention. We can not recommend universal cranial ultrasound screening based on our results. Orv Hetil. 2023; 164(31): 1222-1230.

#3589 OXALATE METABOLISM IN PRIMARY HYPEROXALURIA TYPE 1 TREATED WITH LUMASIRAN IMMEDIATELY AFTER BIRTH: STILL NOT EARLY ENOUGH

Abstract Background and Aims Severe primary hyperoxaluria type 1 (PH1) with rapid onset nephrocalcinosis and renal function loss in early infancy required so far combined liver and kidney transplant. RNA interfering drugs are the new challenge for these children. Here we present the first case of a newborn affected by PH1 treated with RNA-interfering Lumasiran 6 hours after birth. Method Diagnosis of PH1 (homozygous mutation AGXT c.731T&amp;gt;C9 [p.Ile244Thr]) was done at 11 weeks of pregnancy on chorionic villus due to family history. Parents are first cousins, both heterozygous carriers of the mutation. Their first child is homozygous, affected by PH1, in dialysis for massive nephrocalcinosis since two months of life, kidney-liver transplanted at 14 months, with multiple comorbidities, severe retinal oxalate deposition, early ischemic stroke and post-transplant lympho-proliferative disease. Mother blood Oxalate, Glycolate and Urinary Oxalate during pregnancy proved normal (3 umol/L and 4 umol/L; 35 umol/mmol). Fetal morphology at ultrasound was normal, showing a male fetus large for gestational age, due to gestational diabetes, and polyhydramnios. At 37w cesarean section was performed. Birth weight 4120 g; Length 49.9 cm (99° centile for gestational age). Apgar score 9/9. Cord blood and amniotic fluid were obtained for Oxalate dosage and Sanger sequencing for diagnosis confirmation. Umbilical central venous line and bladder catheter were placed for immediate start of infusions and serial sampling. Results PH1 was confirmed due to Homozygous mutation AGXT c.731T&amp;gt;C9 [p.(Ile244Thr)]. Oxalate on cord blood was 15 umol/L (nv &amp;lt;10), on amniotic fluid 55 umol/L (nv 19-71), on first urine 401 umol/mmolCr (nv &amp;lt; 300 umol/mmolCr). Blood Oxalate at 6h of life rose to 32 umol/L, Glycolate to 107 umol/L and urinary Oxalate to 573 umol/mmolCr. Serum Creatinin was normal (0.3 mg/dl). At 6 hours of life the child was treated with Glycolate Oxidase RNAi Lumasiran at the dose 6 mg/kg subcutaneously, in combination with Pyridoxin 10 mg/kg/day. Hyperhydration (240 ml/kg/day) was maintained iv for 16 days in combination with oral water and potassium citrate (500 mg in 500 ml/day) above breast feeding. Blood Oxalate was serially assessed every 48 hrs showing a peak level of 108 umol/l (nv &amp;lt;10) at day 6, higher than the supersaturation level of 60 umol/L, then a gradual decline (65-56-62 umol/L at 10-20-30 days respectively). Lumasiran 6 mg/kd was repeated at 30 and 60 days according to schedule, then at 3 mg/kg every month. After the second dose of Lumasiran a steeper decline of blood Oxalate was observed (31-17 umol/L at 45-60 days respectively) reaching the upper normal limit of 12 umol/L after three doses, at 80 days. Urinary Oxalate in spite of Lumasiran early start rose until a maximum of 4173 umol/mmolCr (nv for age &amp;lt;300 umol/mmolCr) at 13 days and gradually declined to 765 umol/mmolCr at 80 days, after three doses. Blood and urine Glycolate initially paralleled Oxalate then increased after each Lumasiran dose. Renal ultrasound normal at birth, showed only minimal hyperechogenic spots during the first 2 months, then mild bilateral hyperechogenic papillary deposits without signs of nephrocalcinosis/stones. Renal function at 3 months of life is normal (serum Creatinine 0.2 mg/dl); child growth on the higher centiles (7 kg), with no adverse events. Conclusion Blood and urine Oxalate serial analysis in a severe case of PH1 treated immediately after birth show that Glycolate Oxidase inhibition has a latency of at least 15 days, even when no previous deposits are present. In these days extremely high level of urine and blood Oxalate, far higher than supersaturation level, are reached, in spite of normal renal function, hyperhydration, B6 and citrate supplementation. This case confirms that familiar severe forms of PH1 should be treated immediately after birth with Lumasiran in combination with aggressive supportive therapy to avoid irreversible nephrocalcinosis and renal failure. Prenatal treatment of these cases might be considered in future.

Examining CLABSI rates by central-line type

Background: Central-line–associated bloodstream infections (CLABSIs) are linked to increased morbidity and mortality, longer hospital stays, and significantly higher healthcare costs. Infection prevention guidelines recommend line placement in specific insertion locations over others because of the relative risk of infection. The purpose of this study was to assess CLABSI rates by line type to determine whether some central lines had a lower risk of infection and should be recommended over others given similar clinical indications. Methods: At UNC Hospitals, data were obtained on central lines across a 3-year period (FY20–FY22) from the EMR (Epic Systems). Central lines were categorized as apheresis catheters, CVC lines (single, double, or triple lumen), hemodialysis catheters, introducer lines, pulmonary artery (PA) catheters, PICC lines (single, double, or triple lumen), port-a-catheters, trialysis catheters, or umbilical lines. The line type(s) associated with each CLABSI during the same period were recorded, and CLABSI rates by line type per 1,000 central-line days were calculated using SAS software. If an infection had &gt;1 central-line device type associated, the infection was counted twice when calculating the CLABSI rate by line type. We calculated 95% CIs for each point estimate to assess for statistically significant differences in rates by line type. Results: During FY20–FY22, there were 264,425 central-line days and 458 CLABSIs, for an overall CLABSI rate of 1.73 CLABSIs per 1,000 central-line days. Also, 16% of patients with a CLABSI had &gt;1 type of central line in place. Stratified data on CLABSI rates by each central-line type is presented in the Figure. CLABSI rates were highest in patients with apheresis lines (6.22; 95% CI, 3.96–9.35) and PA catheters (6.22; 95% CI, 3.54–10.20), and the lowest CLABSI rates occurred in patients with PICC lines (1.44; 95% CI, 1.19–1.73) and port-a-catheters (1.14; 95% CI, 0.89, 1.45). For both CVC and PICC lines, as the number of lumens increased from single to triple, CLABSI rates increased, from 0.91 to 2.63 and from 0.57 to 1.20, respectively. Conclusions: At our hospital, different types of central lines were associated with statistically higher CLABSI rates. Additionally, a higher number of lumens (triple vs single) in CVC and PICC lines were also associated with statistically higher CLABSI rates. These findings reinforce the importance of considering central-line type and number of lumens to minimize risk of CLABSI while ensuring that patients have the best line type based on their clinical needs.Disclosures: None

665 - Disposable pressure transducer to identify central pressure measurements in umbilical lines for preterm and term infants in the neonatal intensive care unit

665 - Disposable pressure transducer to identify central pressure measurements in umbilical lines for preterm and term infants in the neonatal intensive care unit

Establishing an hTERT-driven immortalized umbilical cord-derived mesenchymal stem cell line and its therapeutic application in mice with liver failure

Acute liver failure (ALF) is characterized by rapid liver cell destruction. It is a multi-etiological and fulminant complication with a clinical mortality of over 80%. Therapy using mesenchymal stem cells (MSCs) or MSCs-derived exosomes can alleviate acute liver injury, which has been demonstrated in animal experiments and clinical application. However, similar to other stem cells, different cell sources, poor stability, cell senescence and other factors limit the clinical application of MSCs. To achieve mass production and quality control on stem cells and their exosomes, transfecting umbilical cord mesenchymal stem cell (UCMSC) with lentivirus overexpressing human telomerase reverse transcriptase (hTERT) gene, the hTERT-UCMSC was constructed as an immortalized MSC cell line. Compared with the primary UCMSC (P3) and immortalized cell line hTERT-UCMSC at early passage (P10), the hTERT-UCMSC retained the key morphological and physiological characteristics of UCMSC at the 35th passage (P35), and showed no signs of carcinogenicity and toxic effect in mice. There was no difference in either exosome production or characteristics of exosomes among cultures from P3 primary cells, P10 and P35 immortalized hTERT-UCMSCs. Inoculation of either hTERT-UCMSC (P35) or its exosomes improved the survival rate and liver function of ALF mice induced by thioacetamide (TAA). Our findings suggest that this immortalized cell line can maintain its characteristics in long-term culture. Inoculation of hTERT-UCMSC and its exosomes could potentially be used in clinics for the treatment of liver failure in the future.

Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma.

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with a relatively good prognosis. However, the prognosis remains poor for elderly patients and those with a significant depth of tumor invasion; thus, novel treatment modalities are needed. The aim of this study was to analyze the impact of cannabidiol (CBD) and its combination with NSAIDs, diclofenac (DIC) and ibuprofen (IBU) on VSCC cells. In this regard, the MTT test was applied for cytotoxicity analysis. Moreover, the influence of CBD, DIC and IBU, as well as their combinations, on apoptosis and cell cycle distribution were analyzed by flow cytometry. The mechanisms of action of the analyzed compounds, including their impact on NF-κB signaling, p53 and COX-2 expression were evaluated using Western blot. This study shows that CBD and its combinations with NSAIDs are cytotoxic to A431 cells, but they also reduce, in a dose-dependent manner, the viability of immortalized keratinocyte HaCaT cells, and human umbilical vein cell line, EA.hy926. Moreover, the compounds and their combinations induced apoptosis, diminished the NF-κB signaling activation and reduced COX-2 expression. We conclude that CBD and its combination with DIC or IBU are promising candidates for the adjuvant treatment of high-risk VSCC patients. However, their impact on non-cancerous cells requires careful evaluation.