Peripheral Line Research Articles

Peripheral Use of Vasopressors in Shock: Clinical Considerations and Recommendations for Use in Obstetrics.

This study aimed to evaluate the safety of peripheral administration of vasopressor agents among patients with circulatory shock. We reviewed the published literature evaluating the use of peripheral norepinephrine in patients with shock and proposed a protocol for use in labor and delivery units. Peripheral administration of norepinephrine is a safe and potentially lifesaving intervention for patients in labor and delivery with extremely low complication rates. Adoption of a protocol for peripheral administration of vasopressors in labor and delivery is safe and may prevent life threatening delays in hemodynamic resuscitation. · Administering vasopressors through a peripheral line is safe and helps avoid delays in care.. · An established protocol is essential for the safe peripheral administration of vasopressors.. · Understanding continuous blood pressure monitoring is crucial for managing critically ill patients..

IV Ciprofloxacin-Induced Phlebitis: Investigating the Impact of Pharmaceutical and Process-Related Factors on Patient Safety

Transient phlebitis is a rare but notable adverse reaction that can occur following intravenous administration of various medications, including ciprofloxacin, an antibiotic recognized for its broad-spectrum activity. This case report discusses a 48-year-old male patient with poorly controlled type 2 diabetes who developed phlebitis after receiving undiluted ciprofloxacin via a peripheral intravenous line. Symptoms emerged within 24 hours, characterized by swelling and redness at the injection site, prompting the discontinuation of the medication. Analysis revealed that improper dilution and rapid infusion rate were major factors contributing to the development of phlebitis. This underscores the importance of adhering to guidelines provided in product information leaflets for intravenous drug preparation and administration. The case emphasizes the critical need for healthcare professionals to follow recommended protocols to reduce the risk of infusion-related complications, especially in patients with underlying comorbidities.

Clinical characteristics and genetics functional analysis of two children with Spinal muscular atrophy

To explore the characteristics of SMN1 gene variants and carry out functional verification for two children with Spinal muscular atrophy (SMA). Two male children with complicated SMA diagnosed at the Children's Hospital Affiliated to Capital Institute of Pediatrics respectively in July 2021 and April 2022 due to delayed or retrograde motor development were selected as the study subjects. Clinical data of the children were collected. Primary culture of skin fibroblasts was carried out, and peripheral blood samples were collected from both children and their parents. Multiplex ligation-dependent probe amplification, combined long-range PCR and nested PCR, and Sanger sequencing were carried out to detect the copy number and variants of the SMN1 gene. Absolute quantitative real-time PCR, Western blotting and immunofluorescence were used to determine the transcriptional level of the SMN gene, expression of the SMN protein, and the number of functional SMN protein complexes (gems body), respectively. This study was approved by the Children's Hospital Affiliated to Capital Institute of Pediatrics (Ethics No. SHERLLM2021009). Child 1, a 1-year-old boy, was clinically diagnosed with type 1 SMA. Child 2, a 2-and-a-half-year-old boy, was clinically diagnosed with type 3 SMA. Both children were found to harbor a paternally derived SMN1 deletion and a maternally derived SMN1 gene variant, namely c.824G>T (p.Gly275Val) and c.884A>T (p.*295Leu). Compared with the normal controls and carriers, the levels of full-length SMN1 transcripts in their peripheral blood and skin fibroblast cell lines were significantly decreased (P < 0.05), and the levels of SMN protein normalized to that of β-actin, and the numbers of gems bodies in the primary fibroblast cells were also significantly lower (P < 0.05). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were classified as likely pathogenic (PS3+PM3+PM5+PP3; PS3+PM3+PM4+PP3). Following the diagnosis, both children had received nusinersen treatment. Although their motor function was improved, child 1 still died at the age of 2 due to severe pulmonary infection. The walking ability of child 2 was significantly improved, and his prognosis appeared to be good. Two cases of clinically complicated SMA have been confirmed by genetic testing and experimental studies, which has provided a reference for their accurate treatment.

Transgenic zebrafish as a model for investigating diabetic peripheral neuropathy: investigation of the role of insulin signaling.

Diabetic peripheral neuropathy (DPN), a complication of diabetes mellitus (DM), is a neurodegenerative disorder that results from hyperglycemic damage and deficient insulin receptor (IR) signaling in peripheral nerves, triggered by failure of insulin production and insulin resistance. IR signaling plays an important role in nutrient metabolism and synaptic formation and maintenance in peripheral neurons. Although several animal models of DPN have been developed to identify new drug candidates using cytotoxic reagents, nutrient-rich diets, and genetic manipulations, a model showing beneficial effects remains to be established. In this study, we aimed to develop a DPN animal model using zebrafish to validate the effects of drug candidates on sensory neuropathy through in vivo imaging during the early larval stage. To achieve this, we generated Tg (ins:gal4p16);Tg (5uas:epNTR-p2a-mcherry) zebrafish using an enhanced potency nitroreductase (epNTR)-mediated chemogenetic ablation system, which showed highly efficient ablation of pancreatic β-cells following treatment with low-dose metronidazole (MTZ). Using in vivo live imaging, we observed that sensory nerve endings and postsynaptic formation in the peripheral lateral line (PLL) were defective, followed by a disturbance in rheotaxis behavior without any locomotory behavioral changes. Despite defects in sensory nerves and elevated glucose levels, both reactive oxygen species (ROS) levels, a primary cause of DPN, and the number of ganglion cells, remained normal. Furthermore, we found that the activity of mTOR, a downstream target of IR signaling, was decreased in the PLL ganglion cells of the transgenic zebrafish. Our data indicates that peripheral neuropathy results from the loss of IR signaling due to insulin deficiency rather than hyperglycemia alone.

A novel murine syngeneic CD8 peripheral T-cell lymphoma model with preclinical applications

Peripheral T-cell Lymphoma (PTCL) represents a heterogenous group of aggressive non-Hodgkin Lymphomas with poor prognostic outcomes and limited treatment options. The development and refinement of therapeutic strategies for PTCL are impeded by a paucity of reliable preclinical models that accurately mimic the disease’s pathophysiology. There is a dire need for more physiologically relevant models for PTCL. Here we describe a spontaneousCD8+ peripheral T-cell lymphoma cell line (LM-23) derived from a 12-week-old female Balb/cJ mouse. Both intravenous and subcutaneous administration of this cell line to syngeneic Balb/cJ mice resulted in rapid establishment of tumor growth. CHOP and anti-PD1 treatment both displayed no benefit to mice in regulating tumor growth. Such results along with its phenotypic characteristics, rapid growth, and metastatic behavior in syngeneic mice highlight its value in studying the elusive disease and discovery of novel therapeutics.

5-nitro-thiophene-thiosemicarbazone derivative induces cell death, cell cycle arrest, and phospho-kinase shutdown in pancreatic ductal adenocarcinoma cells

IntroductionPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options. This study explores the potential of novel 5-nitro-thiophene-thiosemicarbazone derivatives as therapeutic agents for PDAC. MethodsWe evaluated the cytotoxicity of seven derivatives in peripheral blood mononuclear cells (PBMCs) and PDAC cell lines. Promising candidates (PR12 and PR17) were further analyzed for their effects on colony formation, cell cycle progression, and reactive oxygen species (ROS) production. PR17, the most promising derivative, was subjected to additional investigation, including analysis of autophagy-related genes and protein kinase inhibition. ResultsThree derivatives (PR16, PR19, and PR20) displayed cytotoxicity towards PBMCs. PR12 reduced colony formation and G0/G1 cell cycle arrest in PDAC cells. Notably, PR17 exhibited potent activity in MIA PaCa-2 cells, inducing S-phase cell cycle arrest, downregulating autophagy genes, and inhibiting key protein kinases. ConclusionPR17, a 5-nitro-thiophene-thiosemicarbazone derivative, demonstrates promising antineoplastic activity against PDAC cells by potentially modulating cell cycle progression, autophagy, and protein kinase signaling. Further studies are warranted to elucidate the detailed mechanism of action and explore its efficacy in vivo.

Extravasation with methylthioninium chloride

Introduction Methylthioninium chloride is used for multiple treatment purposes and is sometimes administered through peripheral intravenous lines. We highlight the potential adverse effects of methylthioninium chloride extravasation during continuous peripheral intravenous administration. Case summary A 38-year-old woman presented to the emergency department with multifactorial hypovolemic and septic shock. She was treated with a continuous peripheral infusion of intravenous methylthioninium chloride for shock refractory to multiple vasopressors. Images One day after administration commenced, the patient developed blue staining of the left upper arm due to extravasation of methylthioninium chloride proximal to the site of infusion. Further images show its later spread. Conclusion While reported cases of methylthioninium chloride extravasation are rare, it is our preference that methylthioninium chloride should be administered through a central line in cases of continuous infusion due to the risk of potential toxicity from extravasation.

Catheters linked thrombosis in neonates: a single center observational study

BackgroundCentral venous catheters (CVCs) are the major risk factors for neonatal thrombosis that might negatively affect morbidity and mortality in neonates. The aim of the present work was to estimate the incidence of CVC-linked thrombosis, among neonates in the NICU of Alexandria University Maternity Hospital, Egypt, over 1year, and to determine its possible risk factors.MethodsThis observational cohort study involved 134 newborn infants born from July 2020 to July 2021with CVCs insertion during their hospital stay. Patients who had congenital anomalies, had thrombosis unrelated to the implantation of CVCs or died before 7 days of catheter placement were excluded from the analysis. The 134 neonates who met the study’s eligibility requirements had 142 CVCs inserted. Serial ultrasound and Doppler scans on site of venous insertion of catheters were performed.ResultsSeventeen patients with catheter’s thrombosis (12%) were found during the placement of 142 catheters or 1615 CVCs’ days, resulting in an overall rate of 10.5 thrombotic events per 1000 catheters’ days. We constructed a logistic regression model to identify risk factors behind CVC-linked thrombosis. In univariate analysis, femoral central venous lines (CVLs), catheter dwell-time, sepsis, packed red cells (PRBCs) transfusions and low platelet count were risk factors for CVC-linked thrombosis. Nevertheless, only PRBCs transfusion was significant in the multivariate analysis, with OR and 95% confidence level 5.768 (1.013–32.836).ConclusionMany factors should be considered in prediction of patients at risk of thrombosis including sepsis, femoral line insertion, low platelet count and PRBCs-transfusions. In our analysis, PRBCs-transfusion through peripheral intravenous lines (PIVs) was the strongest factor associated with CVC-linked thrombosis.

Prehospital transfusion of labile blood product using intraosseous perfusion with multi-lumen extender: Why not?

French prehospital military medical teams are provided with labile blood products to effectively address hemorrhagic shock. In combat environment, standard good medical practice may limit efficacy of therapeutic goals regarding damage control resuscitation. We present here a case report describing the management of a soldier heavily wounded during a helicopter forward medical evacuation in Sahel region. We report the challenge encountered by medical team using only a humeral intraosseous route available due to severity of lesions and challenging environment. In this configuration, multi-lumen extender enabled transfusion of two units of packed red blood cells and two units of plasma, and analgesia while limiting manipulation and dislodgment of the fragile intraosseous route. This situation, outside of usual good medical practice, raises issues of hemolysis, physicochemical compability of drugs and blood products, and consequences on flow rate reduction. With this case, we emphasize the benefit of multi-lumen extender associated with intraosseous route for early management of heavy casualties in harsh prehospital environment. Literature suggests that hemolysis and physicochemical compability should remain limited. The main issue of this setting consists of flow reduction and can be addressed by prioritizing humeral route, and using counter pressure cuffs, until a second peripheral or central line is available and management can resume without the need for multi-lumen extender.

Dose-Dependent Alterations of Lysosomal Activity and Alpha-Synuclein in Peripheral Blood Monocyte-Derived Macrophages and SH-SY5Y Neuroblastoma Cell Line by upon Inhibition of MTOR Protein Kinase – Assessment of the Prospects of Parkinson’s Disease Therapy

To date, the molecular mechanisms of the common neurodegenerative disorder Parkinson’s disease (PD) are unknown and, as a result, there is no neuroprotective therapy that may stop or slow down the process of neuronal cell death. The aim of the current study was to evaluate the prospects of using the mTOR molecule as a potential target for PD therapy due to the dose-dependent effect of mTOR kinase activity inhibition on cellular parameters associated with, PD pathogenesis. The study used peripheral blood monocyte-derived macrophages and SH-SY5Y neuroblastoma cell line. As a result, we have for the first time showed that inhibition of mTOR by Torin1 only at a concentration of 100 nM affects the level of the lysosomal enzyme glucocerebrosidase (GCase), encoded by the GBA1 gene. Mutations in GBA1 are considered a high-risk factor for PD development. This concentration led a decrease in pathological phosphorylated alpha-synuclein (Ser129), an increase in its stable tetrameric form with no changes in the lysosomal enzyme activities and concentrations of lysosphingolipids. Our findings suggest that inhibition of the mTOR protein kinase could be a promising approach for developing therapies for PD, particularly for GBA1-associated PD.

Cost comparison of four venous catheters: Short peripheral catheter, Long peripheral line, Midline, and PICC for peripheral infusion

Introduction: The use of midline catheters for patients requiring a peripheral IV infusion is sometimes limited by their cost. Although decision trees allow them to be positioned in relation to short peripheral cannulas (SPC), Midlines, and PICCs, their economic impact has not yet been evaluated. A study was conducted to estimate and compare the actual costs of using the three types of catheters for durations of 7, 14, and 21 days. Methods: A budget impact analysis compared midlines or mini-midlines/long peripheral cannulas (LPCs) with SPCs and PICCs for typical medical indications excluding indications requiring central line (infusion of irritant or vesicant drugs): treatment of peritonitis over 7 days, cystic fibrosis infection over 14 days, and meningitis over 21 days. A micro-costing study identified resources used during catheter care procedures (consumables, medical/nursing care, examinations, mechanical complications). The cost of remote systemic complications was estimated from the French national cost study. Literature review compared data based on published complication frequencies. Results: Midline is more economic than the SPC (saving of 39€ over 7 days and 174€ over 14 days), and than the PICC (saving of 102€ over 14 days and 95€ over 21 days). Discussion: Despite a much higher acquisition cost of the Midline than a SPC, the cost of using a Midline is lower. Although this approach cannot be the only argument for choosing a medical device, it can contribute to it in a tense economic context. The micro-costing has been performed in a center placing PICCline using fluoroscopy for catheter tip positioning. The implantation of a PICC with ECG technique does not require an interventional radiology facility and involves significantly lower logistical and personnel costs. This factor is a limitation in this study. However, even with the use of EGC, the cost difference is in favor of Midline.

Development and validation of novel keloid-derived immortalized fibroblast cell lines.

Keloids are a common connective tissue disorder with an ill-understood etiopathogenesis and no effective treatment. This is exacerbated because of the absence of an animal model. Patient-derived primary keloid cells are insufficient as they age through passaging and have a limited supply. Therefore, there is an unmet need for development of a cellular model that can consistently and faithfully represent keloid's pathognomic features. In view of this, we developed keloid-derived immortalized fibroblast (KDIF) cell lines from primary keloid fibroblasts (PKF) by transfecting the human telomerase reverse transcriptase (hTERT) gene. The TERT gene encodes the catalytic subunit of the telomerase enzyme, which is responsible for maintaining the cellular replicative potential (cellular immortalization). Primary fibroblasts from keloid-specific lesional (peripheral, middle, and top) as well as extralesional sites were isolated and evaluated for cell line development and comparative cellular characteristics by employing qRT-PCR and immunofluorescence staining. Moreover, the immortalized behavior of KDIF cell lines was evaluated by comparing with cutaneous fibrosarcoma and dermatofibrosarcoma protuberans cell lines. Stable KDIF cell lines with elevated expression of hTERT exhibited the cellular characteristics of site-specific keloid fibroblasts. Histochemical staining for β-galactosidase revealed a significantly lower number of β-gal-positive cells in all three KDIF cell lines compared with that in PKFs. The cell growth curve pattern was studied over 10 passages for all three KDIF cell lines and was compared with the control groups. The results showed that all three KDIF cell lines grew significantly faster and obtained a fast growing characteristic as compared to primary keloid and normal fibroblasts. Phenotypic behavior in growth potential is an indication of hTERT-mediated immortalized transformation. Cell migration analysis revealed that the top and middle KDIF cell lines exhibited similar migration trend as site-specific PKFs. Notably, peripheral KDIF cell line showed significantly enhanced cell migration in comparison to the primary peripheral fibroblasts. All KDIF cell lines expressed Collagen I protein as a keloid-associated fibrotic marker. Functional testing with triamcinolone inhibited cell migration in KDIF. ATCC short tandem repeat profiling validated the KDIF as keloid representative cell line. In summary, we provide the first novel KDIF cell lines. These cell lines overcome the limitations related to primary cell passaging and tissue supply due to immortalized features and present an accessible and consistent experimental model for keloid research.

Comparison of invasive blood pressure monitoring vs. non-invasive blood pressure monitoring in critically ill children receiving vasoactive agents-a prospective observational study.

The primary aim of this study was to compare non-invasive blood pressure (NIBP) measurement using the automated oscillometric method with invasive blood pressure (IBP) measurement using peripheral arterial line insertion in critically ill children receiving vasoactive agents. Single-centre, prospective cohort study. Tertiary care 15 bedded Pediatric ICU in Urban Indian city. All critically ill children between the ages of 1 month to 16 years with shock on vasoactive medications and with IBP monitoring. Forty children with 1,072 paired BP measurements were incorporated in the final analysis. Among all normotensive children (Total number of paired measurements = 623) receiving vasoactive agents, Bland-Altman analysis revealed an acceptable agreement between Invasive mean blood pressure (MBP) and non-invasive MBP with a bias of -2.10 mmHg (SD 11.35). The 95% limits of agreement were from -24.34 to 20.14 mmHg. In children with hypotension (Total number of paired measurements = 449), Bland-Altman analysis showed disagreement between Invasive MBP and non-invasive MBP i.e., a bias of -8.44 mmHg (SD 9.62). The 95% limits of agreement were from -27.29 to 10.41 mmHg. A limited agreement exists between invasive blood pressure (IBP) and non-invasive blood pressure (NIBP) measurements in critically ill children requiring vasoactive agents. This discrepancy can lead to either an underestimation or an overestimation of blood pressure. While NIBP can serve as a screening tool for hemodynamically stable children, those who are hemodynamically unstable and necessitate the initiation of vasoactive agents should undergo IBP monitoring.

Comparative Study of Acute Stress in Infants Undergoing Percutaneous Achilles Tenotomy for Clubfoot vs. Peripheral Line Placement.

Percutaneous tenotomy of the Achilles tendon is a procedure that is part of the Ponseti method for clubfoot correction. The need to apply general anesthesia or sedation for this procedure is controversial. The objective of this study is to compare the acute stress generated in infants by percutaneous Achilles tenotomy under local anesthesia vs. peripheral line placement. This cross-sectional study compares the discomfort experienced by 85 infants undergoing percutaneous Achilles tenotomy with local anesthesia with that experienced by 39 infants undergoing peripheral line placement. The following parameters were determined: the duration of the procedure, crying time, average crying intensity, and maximum crying intensity. Other data recorded included the infant's age and complications arising during the procedure. The mean ages of these patients were 1.95 and 2.18 months, respectively. The following data were obtained: the mean duration of the procedure for Group A was 8.13 s and for Group B it was 127.43 s; the mean duration of crying for Group A was 84.24 s and for Group B it was 195.82 s; the mean intensity of crying for Group A was 88.99 dB and for Group B it was 100.98 dB; and the maximum crying intensity for Group A was 96.56 dB and for Group B it was 107.76 dB. Percutaneous Achilles tenotomy can be safely performed as an outpatient procedure, under local anesthesia. This method generates less discomfort than peripheral line placement.

Saccharomyces cerevisiae fungemias: how heterogenous is their management?

Saccharomyces cerevisiae is a yeast used mainly as a probiotic for prevention or treatment of diarrhoea. However, the prevalence of S. cerevisiae fungemia has risen over the past years, notably among patients with predisposing factors. This retrospective study presents 21 cases of S. cerevisiae fungemia at the University Hospital of Liege from 2000 to 2022, their clinical relevance and therapeutic management. Each patient presented one or several risk factors prior to fungemia. The isolated strains presented high minimal inhibitory concentration for fluconazole, while MICs for amphotericin B, voriconazole and echinocandins were low. Some patients received antifungal therapy, while for others only central and peripheral lines were removed and probiotics discontinued. The MICs obtained for voriconazole and echinocandins makes them an alternative treatment to fluconazole and amphotericin B as reported in other studies. Since a S. cerevisiae fungemia can induce the same complications as candidemia, follow-up blood cultures should be collected and metastatic foci should be looked for. This study showed an important discrepancy in the clinical management of infections due to S. cerevisiae and highlights the need for guidelines.

Knowledge, Attitude, and Practices Toward Kangaroo Mother Care Among Mothers in a Tertiary Neonatal Care Unit

Aim: To study the knowledge, attitude, and practices of Kangaroo Mother Care (KMC) among eligible postnatal mothers in the postnatal ward (PNW) and neonatal intensive care unit (NICU) of a tertiary neonatal unit in Eastern India. Methods: A cross-sectional survey was conducted among 100 mothers of low-birth-weight babies in our PNW and NICU. As part of the unit protocol, all mothers of eligible babies were counseled about KMC at first contact verbally as well as by using an informative video on KMC. Data was collected using a structured questionnaire after the routine counseling of the mothers on their first visit after delivery. The analysis of the data was done using appropriate statistics. Results: More than three-fourths (83.2%) of mothers had good knowledge of KMC. A good attitude toward using KMC was found in 91.6% of the mothers. Almost all the mothers (98%) knew the correct KMC position, and 12% of mothers had a previous preterm baby and had given KMC. Many mothers felt the small size of the baby, pain after cesarean section, and central or peripheral intravenous lines in the baby were barriers to KMC. Conclusion: The knowledge regarding KMC among mothers whose babies were admitted into the PNW/NICU was good. Though the attitude toward KMC was good, mothers felt there were multiple barriers to initiating KMC.

Characterization of structural, genotoxic, and immunological effects of methyl methanesulfonate (MMS) induced DNA modifications: Implications for inflammation-driven carcinogenesis

Genotoxic DNA damaging agents are the choice of chemicals for studying DNA repair pathways and the associated genome instability. One such preferred laboratory chemical is methyl methanesulfonate (MMS). MMS, an SN2-type alkylating agent known for its ability to alkylate adenine and guanine bases, causes strand breakage. Exploring the outcomes of MMS interaction with DNA and the associated cytotoxicity will pave the way to decipher how the cell confronts methylation-associated stress. This study focuses on an in-depth understanding of the structural instability, induced antigenicity on the DNA molecule, cross-reactive anti-DNA antibodies, and cytotoxic potential of MMS in peripheral lymphocytes and cancer cell lines. The findings are decisive in identifying the hazardous nature of MMS to alter the intricacies of DNA and morphology of the cell. Structural alterations were assessed through UV–Vis, fluorescence, liquid chromatography, and mass spectroscopy (LCMS). The thermal instability of DNA was analyzed using duplex melting temperature profiles. Scanning and transmission electron microscopy revealed gross topographical and morphological changes. MMS-modified DNA exhibited increased antigenicity in animal subjects. MMS was quite toxic for the cancer cell lines (HCT116, A549, and HeLa). This research will offer insights into the potential role of MMS in inflammatory carcinogenesis and its progression.

A Spectrum of Chemoport-Associated Complications and Their Management in Cancer Patients.

Chemotherapy is part and parcel of the multimodality approach to cancer treatment. Chemoports are frequently used to administer chemotherapy, preventing complications associated with the use of peripheral lines. However, chemoports have their own set of complications and can be very debilitating at times. Accurate knowledge and correct technique can help prevent and manage these complications properly. We retrospectively analyzed all patients who underwent chemoport insertion for chemotherapy infusion over three years between July 2020 and June 2023. The patient's profile, type of cancer, the technique of chemoport insertion, complications related to chemoport, and its management were recorded retrospectively from patient records. The total number of patients in our study was 119. The age group of patients ranged from 13 years to 76 years. Of the 119 patients, 55 had breast cancer, 23 had ovarian cancers, 29 had GI cancers including gastroesophageal junction (GEJ)/ stomach/periampullary/colorectal, and 12 had leukemias. The most common intraoperative complication was catheter tip malposition (9.2%). The most common postoperative complications were infection (7.5%), followed by drug extravasation (5.0%), thrombosis (3.3%), wound dehiscence (2.5%), and skin necrosis (0.8%) in decreasing order of frequency. Serious complications such as hemothorax, pneumothorax, air emboli, brachial plexus injury, and pericardial tamponade, commonly reported in the literature, were not seen in any of our cases. Totally implanted venous access devices (TIVAD)/chemoports are indispensable in the management of cancer patients, especially in patients requiring long duration of infusion and prolonged treatment. Although chemoports are associated with a spectrum of complications, proper technique of implantation and use makes it a safe and reliable tool.

Evaluation of the safety and efficacy of peripheral vasopressors to decrease central line placement and associated bloodstream infections.

In 2020, as a result of evidence of demonstrated safety of an initial pilot program, our institution set out to implement a peripheral vasopressor infusion protocol. To evaluate the use of peripheral lines for vasopressor administration to reduce placement of unnecessary central lines and central line days. This is an Institutional Review Board approved, single center retrospective chart review conducted as pre/post-analysis. Our hospital is a quaternary care, level 1 trauma center in Hartford, Connecticut that serves 100,000-120,000 patients annually. Patients >18years admitted to an intensive care unit (ICU) were included if meeting protocol specific inclusion criteria pertaining to moderate expected duration and dose of vasopressor. Patients were excluded if vasculature not supportive of placement of two peripheral intravenous (PIV) sites, PIV sites without brisk blood return, had a limb restriction, or metacarpal line. All analyses were conducted with SPSS v. 26 (IBM; Armonk, NY 2019), using an a priori alpha level of 0.05 such that all results yielding p < .05 were deemed statistically significant. Primary efficacy outcomes of this study are number of central lines placed and number of central line days. The primary safety outcome is the number of extravasation events attributed to peripheral administration of vasopressors. Overall, 146 patients avoided central line placement constituting a 58.4% (p < .001) decrease in central line placement with peripheral vasopressor use. Out of 382 administrations there were a total of 14 extravasation events that occurred with peripheral vasopressor use in the post-intervention group. Implementation was associated with a statistically significant reduction in CLABSI occurrence. The results of this analysis demonstrate that vasopressors can peripherally administered safely, when proximal to the antecubital fossa, at lower doses, and for short durations of infusion with minimal adverse events.

Abstract LB266: AMG510-mediated inactivation of BCL-xL protein promotes Gasdermin-E-dependent pyroptosis in KRAS-G12C mutant non-small cell lung cancer

Abstract Introduction: Studies have shown that molecular targeted therapy can mediate Gasdermin-E (GSDME) dependent pyroptosis. However, GSDME expression is suppressed in many mutated patients, including those with KRAS-G12C-mutated non-small-cell lung cancer (NSCLC). The efficacy of AMG510 against KRAS-G12C inhibition (KRAS-G12Ci) is constrained by tumor recurrence. Pyroptosis is widely involved in the occurrence and development of tumors. However, the role and molecular mechanism of AMG510 in pyroptosis have not been well identified. Here, we demonstrate that inactivation of anti-apoptotic Bcl-2 family members during KRAS-G12Ci treatment enhances pyroptosis, which then promotes the sensitivity of AMG510 in NSCLC. Methods: We assessed pyroptosis using live cells imaging, LDH release assays, ELISA, Western blotting, and flow cytometry. In vitro assays were used to investigate the function of GSDME. Co-culture between peripheral blood mononuclear cells (PBMCs) and KRAS-G12C mutant lung cancer cell lines explored the anti-tumor immunity of cytotoxic T lymphocytes affected by knockdown of GSDME. The molecular mechanism was determined using bulk RNA sequencing, molecular cloning technology, and Western blotting. Results: We demonstrated that KRAS G12Ci treatment promotes cleavage of GSDME, release of high mobility group protein B1 (HMGB1), and LDH, markers of pyroptotic cell death. Additionally, GSDME was significantly downregulated in KRAS-mutated NSCLC compared with patients of KRAS wild type in TCGA cohort, while significantly upregulated after AMG510 treatment and downregulated after AMG510 resistance in vitro assay. We identified that KRAS-G12Ci resulted in the inactivation of BCL-xL, leading to caspase-3-dependent cleavage of gasdermin E. Conversely, amplification of BCL-xL downregulated the expression of GSDME, therefore suppressing the process of pyroptosis. GSDME knockdown in KRAS-G12C mutant lung cancer cell lines showed defective HMGB1 release, reduced caspase-3 viability, and decreased granzyme B and IFN-γ secretion by CD8+ T cells in response to KRAS-G12Ci, and more frequent tumor cell growth. Conclusion: Our findings indicate that GSDME-dependent pyroptosis is a critical determinant of KRAS-G12C-targeted inhibitor AMG510, and through the modulation exerted by the Bcl-2 family protein BCL-xL upon GSDME. These findings suggest that activation of GSDME may provide an effective strategy to sensitize cancer cells to KRAS-G12Ci treatment. Citation Format: Linfeng Luo, Anlin Li, Wei Du, Maojian Chen, JIng Li, Yixin Zhou, Li Zhang, Shaodong Hong. AMG510-mediated inactivation of BCL-xL protein promotes Gasdermin-E-dependent pyroptosis in KRAS-G12C mutant non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB266.